What Do Social Connectedness and the Mediterranean Diet Have in Common?
The earliest publications by Ancel Keys about the health benefits of the Mediterranean diet have emphasized the importance of the close social interactions of people living on the island of Crete in Greece, as well as the health benefits of dietary habits.
Keys described the Mediterranean diet as consumed by people in post WWII Crete in this way: “… homemade minestrone, pasta of all varieties, with tomato sauce and a sprinkling of Parmesan, only occasionally enriched with a few pieces of meat or served with a small fish of the place … beans and macaroni …, so much bread, never removed from the oven more than a few hours before being eaten, and nothing with which spread it, lots of fresh vegetables sprinkled with olive oil, a small portion of meat or fish maybe a couple of times a week and always fresh fruit for dessert.”
While specific ingredients of the Mediterranean diet, like olive oil, fresh fruit, vegetables, and fish have received a lot of attention in terms of the wide-ranging health-promoting effects of dietary fiber, plant-based fats, polyphenols and minimal consumption of red meat, the importance of the social aspect of this dietary pattern has received much less attention.
Keys and many authors, including The Blue Zones author, Dan Buettner, write about the benefits of the Mediterranean diet with regard to longevity, and have emphasized the essential role of close social interactions between people living around the Mediterranean region. I have experienced this social connectedness around food first hand in my visits to Italy, and have often wondered if this non-dietary component of the Mediterranean food culture could outweigh the negative health effects of dramatic changes in lifestyle, including the increased consumption of red and processed meat in today’s Italy compared to the dietary pattern that Keys described in Crete in the 50s. I still have vivid memories of a recent visit to Parma, the origin of Parmesan cheese and Parma ham (prosciutto). While it was nearly impossible to find foods on the menu of restaurants that I would have called typical traditional, largely plant based Mediterranean dishes (e.g. without ham, cheese and lots of pasta), the bustling interactions between friends and family members enjoying their dinner in the many outdoor restaurant or walking around town until late into the night was different from anything I have ever experienced in the United States. And surprisingly, when I compared the life expectancy in different regions of Italy with very different dietary patterns, there doesn’t seem to be a significant difference between the Emilia Romana region of Parma and coastal regions with high fish consumption, suggesting some factors other than dietary ingredients at play..
So how important is social connectedness for the health benefits described for the Mediterranean diet, and for healthy aging, and what are the consequences of social isolation and often associated loneliness? As a matter of fact, there is a lot of science addressing this topic. In a recent interview with Dr. Wayne Jonas, he gave me the following surprising answer:
“For example, the longest study on healthy longevity ever done, gone out of Harvard, still going on, when they looked at all the factors that contributed to remaining healthy and living a long time, the biggest factor was social connections. Deep social, satisfactory connection. The second biggest factor was meaningful activity. …Those were the two biggest factors. Those were bigger than whether you smoked, whether you exercised, even what your diet was like. Not that those lifestyle factors were not important, but they weren’t necessarily the most important”.
I looked up the Harvard Study of Adult Development that Dr. Jonas had mentioned in our interview. This long-running study was started in 1938 with the goal to identify the factors which make people flourish, mentally, physically and spiritually. The co-leaders of the study, Harvard professors Drs. Robert Waldinger and Marc Schultz discussed the results and implications of the study results in a fascinating book, The Good Life: Lessons From the World’s Longest Scientific Study of Happiness, an excerpt from which was published in the January 19, 2023 issue of the Atlantic magazine. Here is a quote from their article: “Loneliness has a physical effect on the body… It can render people more sensitive to pain, suppress their immune system, diminish brain function, and disrupt sleep, which in turn can make an already lonely person even more tired and irritable.”
Research has found that for older adults, loneliness is far more dangerous than obesity. Ongoing loneliness raises a person’s odds of death by 26 percent in any given year. A study in the U.K., the Environmental Risk (E-Risk) Longitudinal Twin Study, recently reported on the connections between loneliness and poorer health and self-care in young adults. This ongoing study includes more than 2,200 people born in England and Wales in 1994 and 1995. When they were 18, the researchers asked them how lonely they were. Those who reported being lonelier had a greater chance of facing mental-health issues, partaking in unsafe physical-health behaviors, and coping with stress in negative ways. Add to this the fact that a tide of loneliness is flooding through modern societies, and we have a serious problem. Recent stats should make us take notice.”
As a matter of fact, the public recently has taken notice of this hidden epidemic. The topic of loneliness and social isolation has recently made the news headlines in the US when United States Surgeon General, Dr. Vivek Murthy, released a new Surgeon General Advisory calling attention to the public health crisis of loneliness, isolation, and lack of connection in the US.
As quoted from Murthy’s report: “Even before the onset of the COVID-19 pandemic, approximately half of U.S. adults reported experiencing measurable levels of loneliness. Disconnection fundamentally affects our mental, physical, and societal health. In fact, loneliness and isolation increase the risk for individuals to develop mental health challenges in their lives, and lacking connection can increase the risk for premature death to levels comparable to smoking daily.”
In a study conducted online that sampled 55,000 respondents from across the world, one out of every three people of all ages reported that they often feel lonely. Among these, the loneliest group was 16-to-24-year-olds, 40 percent of whom reported feeling lonely “often or very often.” …In Japan, 32 percent of adults expected to feel lonely most of the time during 2020. In the United States, a 2019 study suggested that three out of four adults felt moderate to high levels of loneliness.”
According to this report, “The physical health consequences of poor or insufficient connection include a 29% increased risk of heart disease, a 32% increased risk of stroke, and a 50% increased risk of developing dementia for older adults. Additionally, lacking social connection increases risk of premature death by more than 60%. Given the close interactions between our emotions, the immune system and the gut microbiome, it is not surprising that the same diseases which make up the chronic non-contagious disease epidemic are amongst the negative health outcomes of both the lack of social connections and an unhealthy diet.
As explained in detail in my forthcoming The Mind-Gut-Immune Connection, the negative influences of chronic psychosocial stress (generated by loneliness and social isolation) and of chronic dietary stress (in form of the Standard American Diet) interact to alter the gut microbiome leading to systemic immune activation.
In addition to our physical health, loneliness and isolation contribute substantially to mental health challenges. In adults, the risk of developing depression among people who report feeling lonely often is more than double that of people who rarely or never feel lonely. Loneliness and social isolation in childhood increase the risk of depression and anxiety both immediately and well into the future. And with more than one in five adults and more than one in three young adults living with a mental illness in the U.S., addressing loneliness and isolation is critical in order to fully address the mental health crisis in America.”
Murthy’s report continues: “Social connection is beneficial for individual health and also improves the resilience of our communities. Evidence shows that increased connection can help reduce the risk of serious health conditions such as heart disease, stroke, dementia, and depression. Communities where residents are more connected with one another fare better on several measures of population health, community safety, community resilience when natural disasters strike, prosperity, and civic engagement.”
Returning to the Mediterranean diet, the lifestyle associated with this diet and practiced in countries around the Mediterranean would seem to be an effective way to counteract both the widespread social isolation and the detrimental metabolic effects of the Standard American Diet. Eating a home-delivered pizza or pasta alone while watching TV, eating your caprese sandwich while driving to work, or while listening to a presentation at work, will deprive you of the aspect of social connectedness traditionally associated with the Mediterranean diet.
The Surgeon General’s Advisory lays out a framework for the United States to establish a National Strategy to Advance Social Connection. However, until such policies change the national social infrastructure, individuals should become aware of the importance to not only eat healthy food, but also to work actively to maintain family ties, regular relationship with friends, and use food as a social glue to bring us closer together.
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.
Understanding and Treating Irritable Bowel Syndrome
“We all know that the mind plays a role in disease, but it cannot be studied scientifically.”
From the beginning of my medical career, I was interested in understanding how the brain and the mind interact with the body, and how a dysregulation in these interactions can result in a range of medical problems, from heart attacks to unexplained abdominal pain, and from asthma attacks to non-cardiac chest pain. When I tried to find a thesis advisor for my dissertation in medical school in the early 70s, I typically got the answer from the leading professors that “we all know that the mind plays a role in disease, but it cannot be studied scientifically”. Luckily, after 5 failed attempts, I found the right mentor at the Institute of Physiology at the University of Munich, and embarked on a 4-year period of studying the influence of the brain and specifically the sympathetic nervous system on blood flow to the different layers of the heart. Even though I switched my focus from the heart to the gut during my subsequent clinical training in gastroenterology, I never lost my keen interest in studying brain gut interactions.
Around 10% of the US population suffer from chronically recurring symptoms of abdominal pain, discomfort and altered bowel habits, which are the hallmark symptoms of IBS. Even though IBS is the quintessential disorder of brain gut interactions, it has only been very recent that experts of the largest professional IBS organization, the ROME Foundation, came to agree on this definition.
“IBS is a disorder of neurotic housewives.”
What I experienced during these 50 years could fill a whole book with entertaining anecdotes, hard-to-believe statements by leading IBS authorities at the time, and often conflicting dietary and other treatment recommendations. For example, at an international meeting in the 80s, one prominent thought leader referred to IBS as “a disorder of neurotic housewives”, while another stated that it isn’t “a real disorder” in the first place. Then came the long-lasting period of attributing symptoms to disorders of gastrointestinal motility, e.g. altered contractile activity and intestinal transit, followed by a short period postulating an inflammatory process underlying IBS symptoms, and a period obsessed with “excessive intestinal gas production” to today’s theories about the role of an altered gut microbiome. While the new theories about IBS that appeared every few years – including the most recent focus on an altered gut microbiome – captured the imaginations of clinicians and investigators in the field, encouraged the pharmaceutical industry to come up with new medications, and the supplement industry with new microbiome-targeted treatments, my early conceptualization of IBS as a brain-gut disorder was rejected by the majority of IBS experts – until now.
“The Lumpers and Splitters”
While the ROME Foundation aimed to provide a systematic approach to the functional GI disorders by splitting them into some 40+ different separate entities, each of them with its own postulated mechanism and treatment recommendation, we suggested from early on that alterations in brain gut interactions, including increased perception of visceral signals (“visceral hypersensitivity”), and increased stress responsiveness, provided a unifying framework for all the different clinical manifestations affecting every part of the GI tract from the esophagus to the end of the intestine. Paralleling the different concepts about pathophysiology, treatment recommendations over the decades have ranged from drugs aimed at slowing or speeding up transit through the gut (so called motility drugs), and antibiotics (still in widespread use today). Dietary recommendations have ranged from high fiber diets to the today’s promotion of the “low FODMAP diet”, a diet devoid of many fiber-containing foods. Not surprisingly such a diet cannot be recommended for long term use due to its detrimental effects on metabolic health. Along the way have also been a wide range of supplements ranging from pro- and prebiotics to peppermint oil. While each of these treatment approaches has been shown occasionally to lead to a relieve of some IBS symptoms, none of them turned out to be the miracle treatment which had been expected.
“The majority of proposed treatments have not been much more successful than a placebo pill.”
It is ironic that while these various concepts promoted over the years have primarily fueled the careers of investigators, the output of modified classifications by the ROME Foundation and the profits of the pharmaceutical industry, they have not provided consistent and lasting relief for the millions of patients suffering from symptoms of chronic abdominal pain and discomfort. The majority of proposed treatments have not been much more successful than a placebo pill.
Patients who are interested to learn more about simple ways to self-manage their symptoms, may want to try my IBS class. I provide information and treatment recommendations which I have given to hundreds of IBS patients in my clinic over the years. This information is based on research performed at our center at UCLA, as well as by a few outstanding research groups around the world. For a recent summary of this research and a comprehensive concept of IBS pathophysiology, I refer to our recent review article The Neurobiology of IBS. While I have often been told by colleagues that this information is too complicated for patients to understand (!), I still have yet to meet a patient with IBS who didn’t embrace this information, was relieved by finally having a plausible explanation for their “unexplainable” symptoms, and who has not experienced significant symptom improvement from the recommended therapeutic approach.
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.
Is Moderate Alcohol Consumption Beneficial For Your Health?
For decades, scientific studies suggested that moderate drinking was better for most people’s health than not drinking at all, and that it could even contribute to longevity. Supporting this view, a previous meta-analysis of the association between alcohol use and all-cause mortality found no statistically significant reductions in mortality risk at low levels of consumption compared with lifetime nondrinkers. However, according to a recent study, the risk estimates may have been affected by the number and quality of studies then available. A recent publication in the Journal of the American Medical Association has concluded that many of these earlier studies were flawed and that the opposite is true, in particular for women and younger individuals.
“…the risks of dying prematurely increase significantly for women once they drink 25 grams of alcohol a day, which is less than … two 5-ounce glasses of wine.”
This new systematic review and meta-analysis of 107 cohort studies involving more than 4.8 million participants found no significant reductions in risk of all-cause mortality for drinkers who drank less than 25 g of ethanol per day (about 2 Canadian standard drinks compared with lifetime nondrinkers) after adjustment for key study characteristics such as median age and sex of study cohorts.
The review found that the risks of dying prematurely increase significantly for women once they drink 25 grams of alcohol a day, which is less than two standard cocktails containing 1.5 ounces of distilled spirits, two 12-ounce beers or two 5-ounce glasses of wine. The risks to men increase significantly at 45 grams of alcohol a day, or just over three drinks.
“… light and moderate drinkers are systematically healthier than current abstainers on a range of health indicators unlikely to be associated with alcohol…”
Like the majority of food and lifestyle related studies, most studies on the effects of alcohol on health have been observational, meaning they could identify links or associations caused by factors other than alcohol consumption. They could therefore be misleading and did not prove cause and effect. In particular, that light and moderate drinkers are systematically healthier than current abstainers on a range of health indicators unlikely to be associated with alcohol use such as, dental hygiene, exercise routines, diet, weight, and income. At the same time, lifetime abstainers may be systematically biased toward poorer health, including “sick quitters”, or former drinkers, many of whom cut down or stop for health reasons. In addition, people who abstain completely from alcohol are a minority, and those who aren’t teetotalers for religious reasons are more likely to have chronic health problems. These so-called confounding factors and not the moderate alcohol consumption may have caused the more positive health outcomes in several studies.
Another more important confounding factor is the close association of daily, moderate red wine consumption with longevity in so called Blue Zones, regions around the world with an increased percentage of so-called centenarians, e.g. individuals that live into their hundreds without major health problems. A large number of studies has identified several lifestyle factors, including regular moderate physical exercise, food and the regular consumption of 1-2 glasses of red wine. Even though moderate wine consumption has been practiced for thousands of years and is an essential part of the culture of Mediterranean and Latin countries, it may be the intricate association of the Mediterranean lifestyle, in particular the close social interactions, with the consumption of moderate amounts of wine that produce the observed health benefit.
“…wine — and particularly red wine — developed a reputation for having health benefits after news stories appeared around its high concentration resveratrol and other polyphenols.”
In more recent decades, wine — and particularly red wine — developed a reputation for having health benefits after news stories appeared around its high concentration resveratrol and other polyphenols. Polyphenols are large, poorly absorbable molecules which are produced by most plants, providing multiple benefits to the plants’ health, including protection against UV light, pests and drought. Once consumed by humans, these large molecules are converted by our gut microbes into smaller absorbable entities which are beneficial for the health of our gut microbiome, for gut health and for many organs in our bodies, including the brain. In addition to the stilbene Resveratrol, red wine contains different members of the Flavonoid family, including flavanols (also contained in cocoa beans), flavonols (also contained in green leafy vegetables and onions) and anthocyanins (also contained in black and blue berries). Berries as well as the skin of red grapes also have high concentration of resveratrol. It has been suggested that these health promoting molecules contained in wine not only contribute the unique flavor to different wines, but that they are the reason for the health benefit of moderate wine consumption. But the moderate alcohol hypothesis has come under increasing criticism over the years as the alcohol industry’s role in funding polyphenol research has come to light. Newer studies have found that even moderate consumption of alcohol — including red wine — may contribute to cancers of the breast, esophagus and head and neck, high blood pressure and a serious heart arrhythmia called atrial fibrillation. “Regular moderate consumption of red wine (e.g. 2 glasses per day) when embedded into a healthy lifestyle with regular physical exercise, a healthy diet and close social interactions are likely to have a synergistic effect which is good for our physical and mental health.” My personal opinion on this topic is somewhat different from the recommendation based on the recent meta-analysis. Regular moderate consumption of red wine (e.g. 1 glass per day) when embedded into a healthy lifestyle with regular physical exercise, a healthy diet and close social interactions are likely to have a synergistic effect which is good for our physical and mental health. This view is not only supported by a large number of epidemiological studies; thousands of years of experience of people living in the Mediterranean basin practicing such a lifestyle cannot be wrong. For most people chronic stress has become a regular aspect of modern life, regardless if they are aware of it or not. This chronic stress is fueled and amplified by the relentless bombardment with negative news from the media, in particular the internet: the pandemic, catastrophic climate events, political polarization and a raging war in the middle of Europe are just the most recent examples. On top of that, health books, influencers and social media constantly feed us worrisome and conflicting negative information about our food, dietary habits and our health. This situation has led to what Michael Pollan has rightfully called a national eating disorder epidemic adding anxiety and stress to what normally should be one of our most rewarding times in life, enjoying food with family and friends. “Our biology has not evolved in an adaptive way to deal with this type of constant … stress exposure” Our biology has not evolved in an adaptive way to deal with this type of constant and repeated exposure to stress 24 hours a day. The mismatch between our ancient highly effective biological acute stress response systems which is turned on and off quickly by powerful regulatory mechanisms, and this new form of chronic perturbation of the body’s homeostasis (also referred to as allostatic load) is one of the major factors affecting our health. “Acute, often life-threatening stress has been part of human life for millions of years…” Acute, often life-threatening stress has been part of human life for millions of years and there has been enough time in our evolutionary history to perfect our biological stress response systems in a way that has not only kept our species alive through natural disasters, wars, famines and pandemics, but also has resulted in the dominance of planet Earth by our species. There are two such systems in our body: the older immune stress response system and the brain’s acute stress response system, and both are often engaged together. “The engagement of the brain’s and the immune system response generally occurs in synchrony optimizing the outcome.” The immune system typically responds to an invasion of pathogens (microbes that are harmful to us) with the initial engagement of the innate immune system, like dendritic cells, leading to the recruitment of different immune cells and powerful tools of the adaptive immune system, as well as the release of both inflammatory and anti-inflammatory cytokines. The balance between these opposing forces determines the severity and duration of the infection. The brain also responds to a wide range of perturbations ranging from infections, injuries, psychosocial stressors but also from worry about harmful events happening in the future. Depending on the type and severity of the stressor, the brain responds with the engagement of the two arms of the stress response system, the sympathetic nervous system and the release of cortisol by the HPA axis. The engagement of the brain’s and the immune system response generally occurs in synchrony optimizing the outcome. “… the worry about being shot remains a persistent stress for a significant segment of the population” Our organism responds to any situation – in the presence or anticipated to occur in the future – that is perceived as a threat to our integrity and homeostasis by engaging one or both of these stress response systems. While they have evolved and are optimized to respond to infrequent, but life threatening stresses – the poisonous snake, the wild tiger, the severe injury or the infection, for the majority of people in developed countries, these are no longer the kind of stresses we encounter on a regular basis. Unfortunately, the worry about being shot remains a persistent stress for a significant segment of the population as highlighted by the ongoing epidemic of high profile police shootings. “Our metabolism and the mechanisms controlling our eating behavior are simply not equipped to resist the constant bombardment with commercials promoting unhealthy food…” Today’s perturbation of our body’s balance most often comes in form of chronic stressors associated with modern life: The chronic psychological stress on our minds generated by the relentless daily bombardment with negative news, worries about the future, increasing competition, and number of challenges associated with a lower socioeconomic status (in plain language, poverty, food insecurity, health conditions). And at the same time, the dietary stress on our metabolism in form of the unhealthy Standard American Diet. Our metabolism and the mechanisms controlling our eating behavior are simply not equipped to resist the constant bombardment with commercials promoting unhealthy food, the grotesque portion sizes in most restaurants and the unhealthy contents of our food, full of saturated fat, sugar, and added chemicals including non-nutritive sweeteners, residues of pesticides in our vegetables and fruits, and microplastic in our seafood. “The relentless engagement of our stress systems comes at an increasing cost to the health of our bodies and minds.” Unfortunately, these two type of stressors often occur together, in particular in individuals from lower socioeconomic segments of our society. The relentless engagement of our stress systems comes at an increasing cost to the health of our bodies and minds. Evolution had not foreseen these kind of stressors which we have never experienced as a species. While our stress response systems, the sympathetic nervous system and the HPA axis keep responding in the same way that has been so adaptive for human life, chronic hyperproduction of the stress mediators cortisol and noradrenaline, and chronic systemic engagement of the immune system are responsible for many aspects of our current chronic non-infectious disease epidemic as I have described in detail in The Gut Immune Connection. Not everybody responds to these challenges in the same way: the responsiveness of our neurological and immunological stress system is influenced by genetic factors and is programmed during the first 18 years of life, starting prenatally, in utero, and postnatally, and will determine our lifetime risks for developing these common chronic diseases. This will result in a situation where two people exposed to the same kind and severity of stress will respond in very different ways: one will remain healthy and live to a 100 years, the other one developing a chronic disease and dying early. Other important factors that have been shown to influence the outcomes of living in a chronically stressful world is the quality of social interactions, and the adoption of a eudaimonic lifestyle, which means doing meaningful things including doing good for others. If you want to learn more about this topic, you might also be interested in my upcoming book The Mind-Gut-Immune Connection that you can preorder now. “… there has never been a time in which topics like Gut Health, Immune Support, Gut Cleansing and Improvement of Gut Health have been more popular.” Accompanying the popularization of gut microbiome science in the lay media and on the web, there has never been a time in which topics like Gut Health, Immune Support, Gut Cleansing and Improvement of Gut Health have been more popular. Suddenly experts from the fields of functional and integrative medicine, nutrition, and wellness have all jumped on this new trend. Podcasts, master classes, social media posts, and advertisements for supplements, pre- and probiotics, as well as bestselling books have all driven the frenzy around these topics, while scientific evidence from well controlled human studies to support the findings obtained in mouse models have lagged way behind. As a clinician and scientist who has studied the gut, its endocrine, nervous, and immune systems as well as the brain for the better part of my career, it is remarkable to follow this explosion of information and interest. The “advice” that lay audiences get from books and experts on social media implies that they either have to adopt anti-inflammatory measures such as anti-inflammatory diets or supplements, or that they need interventions to boost their immune system. All implying that there is a blunted, inadequate or compromised response of the immune system contributing to many of our chronic health problems. “… maladaptive increase in the engagement of the immune system in response to diet-induced changes in the gut microbiome does play a crucial role in most of the disorders making up our chronic non-communicable disease epidemic.” As I explain in great detail in The Gut Immune Connection, a maladaptive increase in the engagement of the immune system in response to diet-induced changes in the gut microbiome does play a crucial role in most of the disorders making up our chronic non-communicable disease epidemic. The exaggerated, inadequately restrained response of the gut-associated immune system is not only responsible for the number of autoimmune disorders (including inflammatory bowel disorders and celiac disease), allergies (asthma, food allergies) but also for the group of chronic diseases, all of which have been increasing during the past 75 years. Even though there are different immune mechanisms underlying these different groups of disorders, they all share one mechanism, which is the compromised ability of the immune system to turn on the brakes, once activated. An important factor in this compromised braking mechanism is related to an inadequate production of short chain fatty acids from complex carbohydrates by the gut microbiota, and the resulting insufficient activation of a group of immune cells that produce the powerful anti-inflammatory molecule interleukin 10 (IL-10). This insufficient production of the immune system’s own powerful anti-inflammatory molecules can occur long before we are born, or can develop later in life. “… when pregnant women eat a largely plant-based diet rich in fiber, short chain fatty acid-producing microbes thrive, … which not only have an anti-inflammatory effect on the mother’s gut and body, but …. On the developing fetus as well.” Let’s start with what happens during pregnancy. An important component of the maternal influence on the infant’s microbiome and immune system are short chain fatty acids, derived from the fermentation of dietary fiber by intestinal microbes in the mother’s gut. The amounts and types of these molecules that are produced there and transferred to her baby via the placenta depend on the maternal microbial ecosystem, which in turn is shaped by the mother’s diet. As discussed in detail in The Gut Immune Connection, when pregnant women eat a largely plant-based diet rich in fiber, short chain fatty acid-producing microbes thrive, and increased amounts of them, in particular butyrate, not only have an anti-inflammatory effect on the mother’s gut and body, but these same molecules are transferred to the developing fetus as well. Recent research suggests that butyrate not only can counteract inflammation, but also can influence the maturation and reactivity of the fetal immune system. Specifically, they stimulate the development of a population of immune cells (so called regulatory T cells), which produce anti-inflammatory molecules (in particular the cytokine IL-10) crucial for the prevention of inappropriate immune activation in the gut, leading to autoimmune diseases and allergic reactions. Butyrate produced by the mother’s microbiota doesn’t only play a crucial role for the health of the developing fetus. In the adult, diet-induced short chain fatty acid production exerts an anti-inflammatory effect in the context of a leaky gut, reducing both the inappropriate immune activation in the gut, but also preventing the spread of the inflammation to other organs, a process called metabolic endotoxemia. “Reduced butyrate and short chain fatty acid production leading to a hyperresponsiveness of the immune system, may also play a role in the greater susceptibility and clinical course that were observed in some patients with COVID-19 infections. Reduced butyrate and short chain fatty acid production leading to a hyperresponsiveness of the immune system, may also play a role in the greater susceptibility and graver outcomes that were observed in some patients with COVID-19 infections. Individuals with pre-existing metabolic or cardiovascular chronic diseases were more vulnerable to the infection, and hyperreactivity of the immune system (“cytokine storm”) has been associated with more severe and longer lasting symptoms. On the other hand, patients on immunosuppressive medications have NOT been found to be more susceptible to the virus. In summary, our bodies regulate their own immune support very effectively as long as we feed our microbes a healthy diet full of fiber and polyphenols, a group of large molecules targeted at the gut microbes. Even though messages in social media and promotions of “immune boosting” supplements may tell you otherwise, there is no scientific evidence that additional “immune support” or boosting of our immune system is needed. Colorectal cancer (CRC) is the second leading cause of cancer death in the Western world. It afflicts 150,000 Americans, 250,000 Europeans and 1 million people worldwide annually, and nearly one third will die. The global burden of CRC is expected to increase to more than 2.2 million new cases and 1.1 million annual cancer deaths by 2030. Rather than taking a closer look at the root cause of this problem, the response of the medical system to this alarming trend has been the promotion of colon cancer screening without paying much attention to the role of lifestyle factors that have dramatically changed in the past 75 years, in particular dietary changes. Screening with colonoscopies has permitted early detection and recent studies have clearly shown that this early detection is associated with a significant reduction in mortality rates. However, the overall impact of colon cancer screening has been small, particularly among African Americans who shoulder the greatest burden of the disease in the United States. Recently, when I asked an expert on colon cancer screening if individual dietary habits are considered as risk factors to determine how closely individuals with a positive finding on an initial screening colonoscopy have to be followed, the surprising answer was “this would be a great idea”. “…new cases have been increasing in young and middle-aged adults…” As is the case for many of our non-communicable chronic diseases, the burden of CRC is rapidly shifting to younger individuals. In the United States, despite declines in older adults, the incidence has been increasing in young and middle-aged adults with 22% of CRC cases occurring in those younger than 55 years in 2013 to 2017. CRC incidence has been on the rise among young adults aged 20 to 39 years since the mid-1980s, and this elevated risk in generations born in the US after 1950 strongly indicates that widespread changes in early-life exposures, such as diet and lifestyle factors, may be a major factor underlying the upward trend in early-onset CRC. As I have explained in The Gut Immune Connection, colon cancer shows all the hallmarks of a number of diseases that make up the current epidemic of non-communicable chronic diseases affecting all organs in our body, and presenting as such different medical problems as cardiovascular disorders, non-alcoholic fatty liver disease, type 2 diabetes, metabolic syndrome, obesity, autism spectrum disorder, depression, and neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. These various diseases are not only connected with each other (e.g. the presence of one diagnosis often increases the risk for another), but they share the disease mechanism of low grade systemic immune system activation, occur increasingly in younger age groups and developing countries, and are strongly related to dietary habits and other lifestyle factors, including increased exposure to chemicals and certain medications. For example, studies in Japanese Hawaiians, have demonstrated that it only takes one generation for the immigrant population to assume the colon cancer incidence of the host country, e.g. the US, with adoption of the Western diet playing a major role. “…diet-induced changes in the interactions between the gut microbiome and the gut-associated immune system are a key mechanism underlying the current epidemic.” Reviewing the current evidence, I feel strongly that diet-induced changes in the interactions between the gut microbiome and the gut-associated immune system are a key mechanism underlying the current epidemic. It is becoming increasingly clear that one dietary pattern in particular, the Standard American Diet (SAD) contains many of the components responsible for the negative health effects. High consumption of ultra-processed foods, refined sugars (including high fructose corn syrup) and animal products (red meat and animal fats), paired with a greatly reduced consumption of variable fruits and vegetables containing fiber and polyphenols, as well as a low consumption of naturally fermented foods. A body of evidence suggests that the relationship between the SAD and colon cancer risk is multifactorial. In other words, different dietary components play a role. A study published in the journal Nature Communications in 2015 compared the effect of diet on CRC risk in African Americans and rural Africans. The authors of the study focused on the importance of diet in African Americans and to explore the hypothesis that CRC risk is determined by the influence of the diet on the microbiota to produce molecules that either decreased (anti-neoplastic) or increased (pro-neoplastic) the risk of colon cancer. “Animal protein and fat intake were two to three times higher in Americans, whereas consumption of complex carbohydrates and fiber, primarily in the form of resistant starch, were higher in Africans.” They observed that the diets of African Americans here in the United States, and Africans living in rural villages in South Africa, were fundamentally different in preparation, cooking and composition. Animal protein and fat intake were two to three times higher in Americans, whereas consumption of complex carbohydrates and fiber, primarily in the form of resistant starch, were higher in Africans. Looking at colonoscopies, African Americans had more polyps and higher rates of mucosal proliferation. The dietary differences were shown to be associated with profound differences in the gut microbiota. In Americans, the genus Bacteroides dominated, whereas the genus Prevotella dominated in South Africans. The two groups also differed in the functional capacity of their microbes: Africans had higher levels of starch degraders, carbohydrate fermenters and short chain fatty acid (butyrate) producers, while secondary bile acid producers dominated in Americans. It is well known that products of fiber fermentation, in particular the short chain fatty acid butyrate, are anti-inflammatory and anti-neoplastic, while the products of microbial bile acid conjugation, e.g. different types of secondary bile acids, are carcinogenic. These findings suggested two potential mechanisms for diet-associated colon cancer risk: the protective effect of dietary fiber in increasing the production of butyrate, and the pro-neoplastic effect of dietary fat on stimulating bile acid synthesis by the liver. In summary, considerable epidemiological evidence supports an important role of diet in colon cancer risk. However, it is important to keep in mind that the cause of cancer is multifactorial, including several lifestyle factors and exposure to environmental chemicals and toxins. Having had the personal experience of seeing parents and loved ones struggle through the last few years of life, often admitting that they would much prefer to die than to go on with the consequences of physical and mental decline, I wonder about the fascination of scientists to unravel the biological keys to super longevity, and the growing popularity of books and online information dealing not only with how to live to 100 and beyond, but even reach immortality. “…millions of years of evolution on our planet have come up with this universal cycle of birth and death…” Ageing and dying are natural parts of life. Millions of years of evolution on our planet have come up with this universal cycle of birth and death, optimizing reproductive and survival mechanisms, including age-adjusted muscle strength, cardiovascular and pulmonary function, and reaction times at certain ages when there is a particular need for these functions, and a slow functional decline towards the end of life, when they are no longer essential for survival. In my opinion, these are basic facts that we should accept as the wisdom of evolution. So, do we really want to alter a system that has evolved to provide immense adaptive value for us living in harmony with this planet, and risk major disruptions in the planetary ecosystem by trying to change it? And what about the psychological, sociopolitical, and economic problems that rapidly aging societies with low birthrates, like Japan, South Korea and China have been experiencing? ….[should our goal be] to enable healthy aging with minimal medical and surgical interventions within the biological bandwidth?” Or should we primarily be interested in interventions that build on conserved mechanisms of aging, and optimize these systems through lifestyle modifications, with the primary goal being not to prolong the human lifespan beyond its evolutionary programmed upper limit, but to enable healthy aging with minimal medical and surgical interventions within the biological bandwidth? As described by Patricia S. Daniels in the Feb 7, 2023 issue of the National Geographic magazine, two basic mechanisms have been implicated in the natural aging process. According to Daniels, “…one group of theories holds that the body ages because of wear and tear that accumulates in the tissues over the years. Waste products build up in cells, backup systems fail, repair mechanisms gradually break down, and the body simply wears out like an old car. The second group of theories says that aging is driven by our genes—by an molecular clock set to a particular timetable for each species.” As I will discuss in this post, there is evidence for both of these theories. Biologists point out that from an evolutionary point of view, the effects of natural selection greatly decline after reproductive age, as evolution favors genes that are beneficial early in life, putting the body’s resources into reproduction and leaving fewer available for long-term maintenance”. “…current population trends around the world seem to be moving into a different direction as evolution had in mind.” Even though centenarians make up a very small percentage of the relatively young countries China and India, they make the list mainly because of their large populations. However, centenarians make up a larger share of the total populations of rapidly aging Japan and Italy. Today, there are 4.8 centenarians for every 10,000 people in Japan and 4.1 in Italy. By comparison, the US is aging at about half the rate compared to Japan and Italy, partly due to its higher fertility and immigration rates. By 2050, China is expected to have the largest centenarian population, followed by Japan, the U.S., Italy, and India. What is the main reason underlying this rapid aging of some of the most populated countries in the world? What is the main reason underlying this rapid aging of some of the most populated countries in the world? In terms of aging of entire populations, as demonstrated by the countries listed above, the combination of decreasing birthrates and increased longevity seem to be the main factors. But in terms of the rapidly increasing number of centenarians, the answers is not so clear. Humans have obviously not changed genetically in the past 75 years which suggests that non-genetic, environmental or lifestyle factors should primarily be responsible. One of these factors has been the massive multi-trillion interventions in modern medicine and surgery which have greatly reduced mortality from infectious and age-related diseases, without reducing the number of people afflicted by most of these chronic diseases, the so-called prevalence rates. On the contrary, the prevalence of our most common chronic diseases have been increasing over the last 75 years in the US and countries around the world which have adopted sedentary lifestyles and the unhealthy Standard American Diet. In view of this chronic disease epidemic, it is highly unlikely that the increase in number of centenarians is related to the adoption of a healthier lifestyle, in particular diet, regular physical activity and social interactions. Aging affects almost all of the body’s systems: the senses, the digestive organs, the cardiovascular system, the immune system, the bones, the muscles, and even the gut’s microbiome. Interestingly, in a healthy individual, the central nervous system—the brain and spinal cord—is among those least affected by age. In most tissues, the normal decline in function in the absence of neurodegenerative disorders like Alzheimer’s and Parkinson’s disease is not drastic, but it greatly accelerates in situations of chronic stress, unhealthy diets, and disease, as we are witnessing in the form of the unfolding chronic non-communicable disease epidemic, including accelerated cognitive decline. Changes to bones (osteopenia) and muscles (sarcopenia) affect an older person’s daily life perhaps more than anything else. Between the ages of 30 and 60, bone density and muscle mass decrease in both men and women. In industrialized countries, between the ages of 30 and 75, about half the body’s muscle mass disappears, while the amount of fat doubles. Rather than being a normal part of aging, a major reason for this decline in musculoskeletal function is related to the predominantly sedentary lifestyle that modern societies have adopted. The heart, blood vessels, and lungs are durable structures, built for a long lifetime. The fact that so many older people develop heart and lung problems has less to do with the aging process than with lifestyle factors, such as smoking, obesity, consuming an unhealthy diet, and lacking exercise. Many large-scale epidemiological studies are supporting this major role of lifestyle. Several studies have explored the potential role of the gut microbiome in healthy aging. In contrast to our tissues and organs, the microbes living inside of us have their own genome, 100-fold larger than our own. As I have extensively discussed in my book, The Gut Immune Connection, current microbiome research strongly suggests potential connections to many health conditions including obesity, metabolic disorders, inflammation, cancer, and depression. “Throughout the human life span, the gut microbiome follows some predictable temporal patterns…” Throughout the human life span, the gut microbiome follows some predictable temporal patterns, with rapid change from infancy to age three, remarkable stability up until middle age, and then accelerated change starting in late adulthood. Previous studies have found gut microbiome pattern differences between older adults who are lean and physically active compared to their less fit and healthy contemporaries. Other research has connected early development of frailty to less gut microbial diversity. “…older adults who had a more unique, personalized pattern of changes to their GI microbe profile with age also tended to be healthier and live longer…” In a recent study, published in the prestigious journal Nature Metabolism, a group of prominent investigators from several US universities with lead author Tomasz Wilmanski analyzed gut microbiome genetic sequences and a wealth of other health and survival outcomes data from more than 9,000 people between the ages of 18 and 101. The investigators found that older adults who had a more unique, personalized pattern of changes to their GI microbe profile with age also tended to be healthier and live longer than peers with less microbiome divergence. According to this study, the identified microbiome pattern of healthy aging is characterized by a depletion of core taxa found across most humans, primarily the genera Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicted decreased survival in a four-year follow-up. “The loss of core groups of microbes, and the increase in α-diversity reported in long-lived individuals suggest that gut microbiomes may become increasingly unique, to each individual as they age.” Several studies conducted on centenarian populations provided potential insight into gut microbial trajectories associated with aging. One of these demonstrated that gut microbiomes of centenarians (≤104 years of age) and supercentenarians (104+ years) show a depletion in core abundant taxa (Bacteroides, Roseburia and Faecalibacterium, among others), complemented by an increase in the prevalence of rare taxa. Similar findings have since been reported in other centenarian populations across the world, in particular in regions identified as Blue Zones, such as in Sardinian, Chinese and Korean centenarians, relative to healthy, younger controls. Some studies have also reported higher levels of gut α-diversity in centenarians compared to younger individuals, indicating that gut microbiomes continue to develop within their hosts, even in the latest decades of human life. The loss of core taxa, the exact identities of which may vary across different human populations (Bacteroides vs. Prevotella), and the increase in α-diversity reported in long-lived individuals suggest that gut microbiomes may become increasingly divergent, or unique, to each individual as they age. “…those with less diverse gut environments used more medications and were nearly twice as likely to die during the study period.” In the Wilmansky study, people whose gut microbiomes had grown more unique with age were able to walk faster and had better overall mobility than peers who showed less GI microbe changes with age. Plus, those with less diverse gut environments used more medications and were nearly twice as likely to die during the study period. Unsurprisingly, the research team suggested that modern diets like the Standard American Diet, rich in salty, sugary, or fatty processed foods may be responsible for the microbiome changes in less healthy individuals, may be the main factor underlying the observed age-related changes. “…the progressive, exponential increase in centenarians in certain countries in the world, cannot simply be explained by dramatic lifestyle changes.” In summary, a wealth of epidemiological and observational studies support the concept that our bodies and brains have evolved to last up to 100 years at high functional capacity. Obviously, not everybody reaches that goal, depending on variabilities in genes, environmental factors, lifestyle, and access to modern healthcare. Longevity occupies a certain bandwidth, within which people can die at a relatively young age, or live to 100. Where we find ourselves in this wide bandwidth depends a lot on our lifestyle choices, a conclusion supported by a wealth of scientific evidence. The big unanswered question is why we are witnessing a progressive, exponential increase in centenarians in certain countries around the world. In developing countries this increase may in good parts be due to the benefits of modern medicine and public health measures, in the form of antibiotics, vaccinations and increased hygiene. However, the increased longevity is harder to explain in the developed world, which has been experiencing an epidemic of chronic diseases during the last 75 years, driven in large parts by negative lifestyle and environmental factors. How can this epidemic with increased morbidity be associated with a rising number of centenarians? The answers to this question will have major implications for our future. On the other hand, in the developed world, leading a healthy lifestyle is certainly the most effective way to move to the upper limit of this bandwidth without requiring an ever-increasing number of supplements or futuristic genetic engineering. By Emeran Mayer, MD, Hyo Jin Ryu and Ravi Bhatt IBS is one of the most common disorders of brain-gut interaction globally, with prevalence rates between 5 and 10% for most Western countries and China. In contrast to many chronic non-communicable diseases, such as metabolic, neurological, cardiovascular and some forms of cancer, which we have often discussed in this blog, there has been no progressive increase in prevalence during the past 75 years. “Based on questionnaire data, women are 1.5–3.0 times more likely to have IBS.” Based on questionnaire data, women are 1.5–3.0 times more likely to have IBS, reflecting a prevalence in women of 14% and in men of 8.9%. However, based on healthcare system utilization, women are up to 2–2.5 times more likely to see a healthcare provider for their symptoms. Based on the current symptom criteria, IBS is defined by chronically recurring abdominal pain associated with altered bowel habits in the absence of detectable organic disease. IBS symptoms can be debilitating in a small number of patients, but are mild to moderate in the majority of affected individuals. Based on this definition, other frequently associated somatic or visceral pain and discomfort, as well as anxiety and depression are considered so called comorbid conditions. “IBS is commonly associated with anxiety, depression, and other types of pain…” The gut-restricted definition of the Rome criteria overlooks the fact that a large number of individuals who meet diagnostic criteria for an anxiety or depressive disorder have IBS and vice versa, and a majority of IBS patients show elevated levels of trait anxiety and neuroticism, or meet diagnostic criteria for an anxiety disorder. Currently, the commonly associated psychiatric and somatic symptoms are generally referred to as comorbidities, separate from the primary GI diagnosis and not present in all patients. However, detailed patient histories, frequently reveal symptoms of abdominal discomfort, anxiety and behavioral disturbances starting in early childhood in a majority of patients. “IBS has genetic abnormalities in both the brain and in the little brain of the gut…” A large recent genetic epidemiological study has provided an intriguing explanation for the cooccurrence of abdominal and psychiatric symptoms in IBS patients on the basis of several shared gene alterations (so called single nucleotide polymorphisms or SNIPs). These new findings are consistent with genetic vulnerabilities affecting both the central and the enteric nervous system, and argue against the long held linear pathophysiological concepts that emotional factors may cause IBS symptoms, or that chronic IBS gut symptoms lead to anxiety and depression. “Traditional understanding of IBS mechanisms has been limited and restricted to gut symptoms…” Much of research and drug development in IBS patients has been based on descriptive and symptomatic features, rather than on biology-based disease definitions. These definitions suggest a core abnormality shared by all IBS patients (chronic, recurrent abdominal pain) as well as heterogeneity based on self-reports of predominant bowel habit. However, a comprehensive identification of distinct biology-based subgroups of patients including those based on sex, with different underlying pathophysiological components and differential responsiveness to specific therapies, has not been achieved. In our recently published review article in the prestigious journal Molecular Psychiatry, we discuss the evidence supporting an integrative brain gut microbiome (BGM) model. This model incorporates a large body of evidence from studies on peripheral and central neurobiological disease mechanisms, brain and gut targeted influences of stress and the environment, and results from recently reported large scale genetic analyses with relevance for neuronal dysfunction of the central nervous system and the enteric nervous system (the “little brain” of the gut). The proposed model is consistent with the frequent comorbidity of IBS with other so-called functional gastrointestinal disorders affecting the esophagus, stomach, and other gut areas, and with other chronic pain outside of the gastrointestinal tract, and psychiatric disorders, in particular with anxiety. We also discuss the implications of this model for a better understanding of the biology underlying IBS symptoms and for the development of more effective multidisciplinary treatment approaches. Studying the bidirectional interactions between the brain and the gut in health and disease has been the focus of my 40 years in academic medicine, an interest that was preceded by my research on the interactions between the brain and the heart during my dissertation in Medical School. From the beginning, I realized that irritable bowel syndrome (IBS) was the quintessential disorder of altered brain gut interactions, a concept that was virtually ignored by my colleagues in gastroenterology (“a disorder of neurotic housewives”) and which was a difficult research area to get funding for. At the time, patients were equally reluctant to accept the brain gut interaction model, as they were concerned it would reinforce the widespread prejudice that IBS was all in the head, and not a real disorder. After spending several decades of NIH- and philanthropy-supported research combined with close clinical interactions with patients suffering from brain gut disorders, from the esophagus, stomach to the large intestine, I was able to obtain a generous gift from the Oppenheimer Family Foundation to establish the Center for Neurobiology of Stress and Resilience. I felt confident that the brain-gut model was able to fully explain the development and symptoms, and provide a rational treatment approach to my patients with IBS. It was particularly rewarding that some 40 years after I had first published and lectured about altered brain-gut interactions, the field gradually accepted our original concept and suddenly started referring to these syndromes for the first time as “disorders of gut–brain interaction, related to any combination of the following: motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered Central Nervous System.” The story took a new turn after several intriguing animal studies were published in the literature, which suggested that microbes living in the gut may play a significant role in these brain-gut interactions as well. Although initially skeptical about these findings, together with my colleague Dr. Kirsten Tillisch, I performed the first research study in healthy human participants that confirmed the ability of microbes (given as a probiotic cocktail) to communicate with the brain. Following these initially startling findings, our group published close to 100 manuscripts strongly suggesting a link between the 40 trillion microorganisms in our gut and structure and function of the brain. My research interest rapidly expanded beyond IBS to other putative brain-gut-microbiome disorders such as autism spectrum disorders, early cognitive decline, Parkinson’s disease and inflammatory bowel disorders. Collaborations with investigators with clinical and research interests in these disorders developed across the UCLA campus and beyond, to investigators at USC, UCSD, Duke University and Baylor University. Based on these collaborations and the growing scientific interest in the field of brain-gut-microbiome interactions, I elicited the interest of the chief of the Vatche & Tamar Manoukian Division of Digestive Diseases at UCLA, Dr. Eric Esrailian, to support the development of a translational research center. After two years of hard work to bring together a group of outstanding investigators working in different areas of medicine on the role of the gut microbiome, I became the founding director of the new center, and a dream came true when Andrea and Donald Goodman and Renee and Meyer Luskin made a $20 million gift to establish the UCLA Goodman–Luskin Microbiome Center. This new center will facilitate multidisciplinary collaborations among experts across the campus on the role of the human microbiome in health and disease. By funding senior faculty, drawing talented new researchers into the field, and building a strong infrastructure for these studies through the development of core facilities, the center will work to identify the microbiome’s role in disease prevention and the body’s immune response with the goal of developing new treatments for a range of conditions including inflammatory and irritable bowel diseases; obesity and eating disorders; neurodevelopmental and neurodegenerative diseases such as autism, Alzheimer’s and Parkinson’s disease; liver disease, substance use and psychiatric disorders. The new center, based in the UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, will bring together researchers from across the UCLA campus in interdisciplinary efforts to study how the trillions of microorganisms that inhabit the human gut are implicated in wide-ranging health-related conditions — and how those findings can be translated into new strategies for prevention, treatment, and health promotion. Looking back over the past 40 years, I couldn’t be more excited that my interest in brain body interactions which started in Medical School persisted over nearly half a century and culminated in the publication of more than 415 manuscripts, two bestselling books, an upcoming PBS documentary and the launching of a cutting-edge research center in an area with immense implications for health and disease. I am glad to have stuck with my gut feelings! As the COVID-19 pandemic has engulfed the world, there has never been a time in which topics related to gut health have been more popular. Suddenly self-declared experts from different fields of medicine, nutrition and wellness have all jumped on this new trend to explain old symptoms (such as bloating and abdominal distension) and to promote controversial novel treatments. Podcast, master classes, social media posts and advertisements, bestselling books have all driven the frenzy around topics like SIBO, special gut friendly diets and cleansing protocols, while scientific evidence from well controlled human studies have been lagging behind. I am convinced that a significant number of individuals striving for improved gut health are suffering from IBS or related disorders of brain gut interactions. In this post, I would like to focus on one such topic: Small intestinal bacterial overgrowth, better known by its acronym SIBO (other references: 1, 2). “There are few concepts and syndromes in Medicine and particularly in Gastroenterology which have gone through a similarly remarkable historical transformation as SIBO”. There are few concepts and syndromes in medicine, and particularly in Gastroenterology, which have gone through a similarly remarkable historical transformation as SIBO. The term first emerged in the literature more than 80 years ago and was a relatively rare diagnosis. However, the concept was adopted more recently not only by functional and integrative medicine practitioners and by the lay media, but also by the medical establishment and the pharmaceutical industry. SIBO has been promoted as a diagnosis explaining some of the most common symptoms of abdominal discomfort such as bloating, abdominal distension and altered bowel habits. The concept has fueled a whole new “industry” of breath testing, and most worrisome, has led to the widespread and in my opinion totally unnecessary use of antibiotic treatments for symptoms most likely unrelated to gut microbes. “…the diagnosis and overall conception of SIBO has become mired in uncertainty and controversy…” SIBO is a clinical disorder that was first described in the 1930s in patients with serious symptoms of malabsorption, bloating, abdominal pain, and diarrhea, following surgical alterations of the gastrointestinal tract. However, since these early descriptions, the concept of SIBO has undergone significant change and challenges in light of emerging insights and speculations from studies into the gut microbiome. The diagnosis of SIBO which originally was limited to a small number of individuals with a specific medical history, has all of a sudden been given to a large number of patients complaining of such common, non-specific symptoms of abdominal bloating, sensations of gas and irregular bowel movements, and is now widely used as a seemingly plausible explanation for many IBS symptoms. However, as well summarized in a recent review article by Bushyhead and Quigley, the diagnosis and overall conception of SIBO has become mired in uncertainty and controversy, as there remains a lack of consensus or “gold standard” for diagnosis, an absence of causality to clearly link clinical symptoms to alterations in the gut microbiota (“dysbiosis”). In addition, the often-prescribed treatment with antibiotics is highly controversial. “…there is currently no universally acknowledged or validated ‘gold standard’ for diagnosis, and no FDA-approved medications.” Although there is no specific symptom of SIBO, patients given this diagnosis generally present with abdominal pain and distension, bloating, flatulence, and diarrhea, a nearly identical symptom complex as reported by IBS patients. Because these symptoms are neither exclusive to, nor predictive of SIBO, and SIBO is often treated with antibiotics, one would expect that such a diagnosis should only be made based on objective, generally accepted, and validated biological tests. However, despite recent advances in the scientific community’s understanding of the microbiome, there is currently no universally acknowledged or validated “gold standard” for diagnosis, and no FD-approved medications. Even though several tests are available and commonly used, including the direct analysis and quantification of small bowel microbiota and various breath tests measuring the production of hydrogen and methane by intestinal microbes, the validity of all these tests has been questioned and has generated substantial controversy. According to a North American Consensus Statement, such test results should be interpreted with caution, and most importantly, in my opinion should never be used as justification to prescribe antibiotics . Surprisingly, although there are no Food and Drug Administration–approved medications to treat SIBO, the mainstay of treatment has been oral antibiotics. Given the well-known serious risks of antibiotic therapy– in particular when administered repeatedly- such as reduction of gut microbial diversity, the promotion of drug-resistant bacteria and the development of Clostridium difficile colitis, one would expect that data on the efficacy of antibiotics for SIBO should be unambiguous. Unfortunately, antibiotic regimens for SIBO have, in general, been poorly studied, largely in trials involving small numbers of patients and lack of placebo controls. For example, a systematic review and meta-analysis of rifaximin, a popular, nonabsorbable antibiotic, demonstrated that the overall eradication rate (based on the controversial breath tests mentioned above) was only about 70%. Importantly, the authors of the study noted that the quality of included studies was generally poor, as only a single study was placebo- controlled. Other treatment modalities that may have a theoretic benefit in restoring healthy GI microbiota such as changes in diet, pro- and prebiotics and even fecal microbiota transplantation (FMT) have not been adequately studied for the treatment of SIBO. “…the most problematic claim relating to the diagnosis of IBS has been its implication in the pathogenesis of IBS.” As if the topic of SIBO is not controversial enough, the most problematic claim relating to this diagnosis has been its implication in the pathogenesis of IBS. An early study demonstrating both a higher prevalence of positive lactulose breath tests in patients with IBS (thought to reflect abnormal numbers of gut microbes in the small intestine) in comparison to healthy control subjects and significant improvement in IBS symptoms following normalization of breath tests with antibiotic therapy suggested a strong association between IBS and SIBO. However, a systematic review and meta-analysis of SIBO in IBS challenged the validity of this association, and put both the validity of the breath test as well as the diagnosis of SIBO into question. Significant problems in study design and reporting, as well as the possibility that a positive lactulose breath test may simply signify an abnormally fast transit time through the small intestine. As there is some suggestion that the pathophysiology of IBS entails abnormal colonic rather than small bowel fermentation of complex carbohydrates, it is possible that the efficacy of antibiotic treatments in reducing bloating symptoms in some IBS patients is due to an impact on colonic rather than small bowel bacterial populations (it is worth noting that a subgroup of IBS patients actually reports a worsening of their symptoms after antibiotic treatment). In view of the well demonstrated hypersensitivity of the colon to distension, even a small reduction of normal intestinal gas production by the colonic microbiota could lead to some reduction in symptoms of bloating and gas. As the involvement and precise mode of action of rifaximin in SIBO remains poorly understood, it has been suggested that the effect of the drug on bacterial numbers may be minimal and effects may be related more to perturbations of bacterial metabolism. However, to date this remains a speculative hypothesis. “…it is not possible to make any valid conclusions about a putative role of intestinal microbiota, SIBO and IBS”. In summary, both the relationship between SIBO and altered intestinal gut microbial density, and the association between SIBO and IBS remains controversial. Whether current testing methods accurately reflect SIBO, and whether abnormal breath test results are causally related with IBS or IBS-like symptoms remains open to question. Because SIBO lacks a gold standard for diagnosis, and IBS is a diagnosis based on symptom criteria (the so-called Rome criteria) and of exclusion that lacks a validated biomarker, it is not possible to make any valid conclusions about a putative role of intestinal microbiota, SIBO and IBS. In my opinion, future research focused on defining the normal small bowel microbiome with novel genomic and metabolomic technologies, and on the clinical utility of breath tests is required before making a valid diagnosis of SIBO and before routinely ordering the available breath test. It shouldn’t come as a surprise to the readers of this post, that I have never made a diagnosis of SIBO in any of my patients, who did not have any of the established risk factors mentioned above, nor have I treated any IBS or IBS-like symptoms with antibiotics. As explained in a previous post My approach to patients is to take advantage of the gut’s own regulatory mechanisms, including a high fiber diet to assure normal transit of food through the small intestine, reduction or elimination of certain food items that reproducibly increase GI discomfort, and the unique gut cleansing motility patterns (“migrating motor complex”) to keep a normal gradient of microbial density throughout the gut. By Emeran Mayer, MD and E. Dylan Mayer If you have been following a gut- and brain-healthy diet, such as the traditional Mediterranean diet or a Pescatarian diet, you already know that seafood and plant-based foods should be your main sources of meat, replacing red meat. Seafood and poultry should make up about 25% of your total dietary intake. Importantly, you should enjoy the fish without being obsessed with fears of consuming toxins with your meal. “Fish are a lean, healthy source of protein and some of them deliver those heart- and brain-healthy omega-3 (also called n-3) fatty acids that [are good for your brain].” Fish are a lean, healthy source of protein–and the oily kinds, such as salmon, tuna, and the family of small fish such as sardine, mackerel, and anchovies–deliver those heart- and brain-healthy omega-3 (also called n-3) fatty acids that you should be getting in your diet. Studies have shown that while consuming a higher ratio of n-6 to n-3 fatty acids tends to promote inflammation, consuming a more balanced ratio can reduce inflammation. In addition, omega-3 fatty acids have been shown to promote neurogenesis (the development of new nerve cells) in a particular region of the hippocampus, the dentate gyrus and there is a strong correlation between omega-3 intake and hippocampal-dependent memory tasks. In the traditional Western diet, polyunsaturated fatty acids (PUFAs) are currently consumed at a ratio of approximately 1:16, whereas it has been estimated that our ancestors consumed a diet with a ratio closer to 1:1. Smaller, fatty fish, like sardines have the highest concentration of omega-3 fatty acids as a consequence of their consumption of omega-3 rich algae. By feeding on the small fish, larger fish like salmon enrich their meet with omega-3 fatty acids. So the decision to select fish with high omega-3 concentration is an easy one. However, there are two additional considerations that you should consider before making your choice. The fish should have low levels of contaminants in particular mercury and PCBs, and it should come from a sustainable fishery, and should not use fishing methods damaging other ocean species. “Fortunately, there are trustworthy sources of information which can help you chose the right fish…” Fortunately, there are trustworthy sources of information which can help you to navigate this dilemma, such as The Blue Ocean Institute and Seafood Watch, the program run by the Monterey Bay Aquarium. These programs have combined data from leading health organizations and environmental groups such as the Environmental Defense Fund (EDF) to come up with a list of seafood that’s good for you and good for the environment. The following is adapted from an excellent blog by Brierley Wright, published by One Medical, a national, modern primary care practice pairing 24/7 virtual care services with inviting and convenient in-person care at over 100 locations across the U.S. According to Seafood Watch, there are six fish/shellfish that are healthy for you and the planet. 1. Farmed Oysters 2. Wild caught Pacific Sardines 3. Wild caught Alaska Salmon 4. Farmed Freshwater Coho Salmon 5. Farmed Rainbow Trout 6. Troll- or pole-caught Albacore Tuna from the US or British Columbia Fish to Avoid A number of environmental organizations have advocated taking many fish off the menu. The large fish listed below are just six examples of popular fish that are both depleted or threatened by extinction and, in many cases, carry higher levels of mercury and PCBs. Unfortunately, many restaurants continue to serve these fish on their menus and customers pay high prizes for what they think is a special treat. 1. Bluefin Tuna 2. Chilean Sea Bass or Patagonian Toothfish) 3. Grouper 4. Monkfish 5. Orange Roughy 6. Salmon (farmed) 7. US freshwater fish – Hot off the press “Three criteria make it relatively easy for an informed consumer to decide which fish to buy” In summary, using the 3 criteria of health benefit, low contamination and sustainability makes it relatively easy for an informed consumer to decide which fish to buy. While many popular fish types are on the Avoid List, the top three choices for you and the planet are small fatty fish, oysters and wild caught Alaskan salmon. Depression is one of the most common mental disorders experienced worldwide with an average lifetime prevalence of 11–15%. As I discussed in The Gut Immune Connection, about 160 million people suffered from major depressive disorder in 2017, young people being the highest risk group. A Blue Cross Blue Shield report showed that in 2016, 2.6% of youths between twelve and seventeen years of age were diagnosed with major depression, a 63% increase from 2013. In addition to these disturbing numbers, the prevalence of depression has doubled and, in some countries, even tripled during the COVID-19 pandemic, suggesting a strong role of environmental factors (the so called “exposome”) in its pathogenesis. The importance of the exposome which includes lifestyle, diet, and exposure to chemicals is further supported by the low to moderate heritability and the small effects of genetic variants identified in large genome-wide association studies of depression. “…the prevalence of depression has doubled and, in some countries, even tripled during the COVID-19 pandemic…” Despite a wealth of preclinical and clinical knowledge published during the past decades, pharmacologic treatment options, based primarily on the prevalent disease model implicating an imbalance of monoamine neurotransmitters like serotonin, dopamine, and norepinephrine, are sub-optimal with most antidepressants performing only marginally better than placebo. In the hope to overcome these limitations, researchers have expanded the traditional narrow focus on these monoamine neurotransmitters and strategies (in particular reuptake inhibitors for serotonin, like SSRIs and norepinephrine (NSRIs), to other disease mechanisms and treatment strategies, such as diet (nutritional psychiatry), psychedelic compounds (like ketamine or psilocybin) and the microbiome. “…animal studies suggest that the gut microbiota might have impact on the neurobiological features of depression.” Based on a series of paradigm shifting preclinical studies in mice, the gut microbiome has emerged as another promising candidate in the pathophysiology of human depression. Several animal studies suggest that gut microbiota might have an impact on the neurobiological features of depression. For example, a study showed that transferring gut microbiota from depressed human patients to “germfree” rats without a gut microbiome showed that the recipient animals developed depression-like behaviors suggesting (but not proving) that gut microbiota may be causally involved in the development of depression. However, there have been very few studies systematically exploring the association between gut microbiome and depression in humans. Further, the existing studies are based on very small samples, lacking statistical power to detect robust and reproducible associations. The majority of published studies in humans did not adjust for confounding lifestyle factors and medication use, which are known to modify the gut “Two large recent studies have confirmed the association of a group of gut microbes with symptoms of depression.” In a recent study, published in the prestigious journal Nature Communications, a team of European investigators aimed to overcome limitations of earlier studies by investigating the association of fecal microbiome diversity and composition with depressive symptoms in 1,054 participants from a large existing data set (the Rotterdam Study cohort) and validate these findings in another data set of 1,539 subjects (the Amsterdam HELIUS Cohort). In this impressive study, the investigators identified an association of thirteen microbial taxa with depressive symptoms. These microbes are known to be involved in the synthesis of butyrate, an anti-inflammatory short chain fatty acid, and the central neurotransmitters glutamate, serotonin, and gamma amino butyric acid (GABA), which are molecules long implicated in the pathophysiology of depression. Based on their findings, the author suggested that the gut microbiome composition may play a key role in depression. In a companion paper, the same group of investigators analyzed samples from 3211 individuals from the same HELIUS cohort, with the aim to characterize gut microbial changes and their associations with depressive symptoms in 6 ethnic groups (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan), living in the same urban area. While gut microbial diversity predicted depressive symptom levels, these associations did not differ between ethnic groups. Bacterial genera associated with depressive symptoms belonged to multiple microbial families. In summary, analyses of a large and ethnically diverse population demonstrated robust associations between features of the gut microbiome and depressive symptoms. These associations were largely invariant across ethnic groups and withstood adjustment for a uniquely large set of potential confounders, including demographic, behavioral, and medical factors. “Is current evidence enough to establish some of these microorganisms as causing or contributing to depression?” When viewed together, a growing number of well-designed high-quality studies in large human data sets have demonstrated a significant association of a group of gut microbes with known functions and symptoms of depression. Is it enough to establish some of these microorganisms as causing or contributing to depression? The answer is yes and no. The preclinical and clinical evidence published over the past few years is certainly highly suggestive of a causal relationship. The identification of microbes capable of producing neurotransmitters involved in depression, and in anti-inflammatory butyrate provides plausibility of the findings. But the proof can only come from longitudinal intervention studies showing that an intervention-related change in the gut microbial alterations in patients with depression is associated with an improvement of clinical symptoms. For ethical reasons, it is obviously not possible to use the same strategy used in animal models, in which the transplant of fecal material from a donor mouse with depression-like behavior results in depression symptoms in the recipient. If the altered gut microbiome does play a clinically relevant change in depression, the question is why has the prevalence of depression increased in the last 10 years, particular in younger patient groups, and most dramatically during the pandemic? Which lifestyle changes that have a strong influence on the gut microbial ecosystem may be underlying this increase in symptoms? Is it the same diet-related systemic immune activation that has been implicated in the different diseases of the chronic non-communicable disease epidemic? On the other hand, well characterized brain changes in animal models of depression and in human patients are associated with well-studied changes in the top-down influences of the brain on the gut and its microbiome. In my opinion, it is equally likely that these brain to gut influences, mediated by the autonomic nervous system and the central stress system are responsible in part for the observed microbiome changes. In my personal view, there is still a long way to go before we can say for sure that the gut microbiome plays a role in depression which is causative and clinically relevant, and that interventions targeted at the gut microbiome are effective enough to be clinically meaningful, and don’t simply represent a placebo response. Extra-virgin olive oil (EVOO) is one of the key health-promoting ingredients of the traditional Mediterranean diet, even though other dietary as well as lifestyle factors are likely to contribute to the health benefits of this diet, including but not limited to a high percentage of plant-based foods (high in vitamins, polyphenols and fiber), low red meat consumption and regular consumption of seafood (with a high ratio of omega-3 to omega-6 fatty acids). EVOO has become a popular component of gut and brain healthy recipes. EVOO not only adds a delicious flavor to your salad and vegetables, but its health benefits have been reported from preclinical and several epidemiological clinical studies. Even though well controlled clinical trials with EVOO are not available, these benefits may be applicable to a wide range of metabolic disorders and cardiovascular diseases, which are all part of the current chronic non-communicable disease epidemic. “…current evidence suggests benefits are largely related to polyphenols and vitamin antioxidants—vitamins A and E—found in the oil.” In addition to the high concentration of monounsaturated fatty acids (primarily oleic acid), evidence suggests that the high content of polyphenols in some of these oils (primarily oleuropein and hydroxytyrosol) contribute to the observed health benefit. As explained many times in this blog, the majority of polyphenols don’t act as antioxidants when consumed, but exert their health benefit with the help of the gut microbiome, and research suggests this may be true for oleic acids, too. Oleic acid is the predominant fatty acid in olive oil—73 percent of its total oil content—while 11 percent is polyunsaturated, such as omega-6 and omega-3 fatty acids. Monounsaturated fatty acids (MUFAs) are quite resistant to high heat, making EVOO a healthy choice for cooking. Traditionally, the high content of MUFAs was considered to be responsible for the protective effects of EVOO, but current evidence suggests benefits are largely related to polyphenols and vitamin antioxidants—vitamins A and E—found in the oil. “…the concentration of polyphenols in EVOO ranges from 50 to 800 milligrams per kilogram…” As many as thirty different polyphenol molecules have been identified in different olives. Furthermore, the concentration of polyphenols in EVOO ranges from 50 to 800 milligrams per kilogram, and the amount of polyphenols in EVOO depends on the region where the olives were grown, corresponding differences in climate, soil composition, degree of ripeness when harvested, and the oil-extraction process. In addition, the phenolic fraction of olive oil can vary greatly among different types of olives. As a result, it can be a challenge to figure out which olive oil to buy in order to get the full benefit in terms of both flavor and polyphenols. And keep in mind, not every brand of EVOO containing the label Made in Italy contains the desired amount of polyphenols. The olives for many marketed brands of EVOO are grown in other Mediterranean countries but pressed and bottled in Italy. “…olive trees started to grow in the southeastern Mediterranean basin more than six thousand years ago…” I learned more about olive oil a couple of years ago, when I visited my friend Marco Cavalieri, the owner of Le Corti Dei Farfensi in Fermo, on the picturesque Adriatic coast of Italy. In addition to his wines, Marco produces EVOO from eight-hundred- year- old olive trees, using a wide variety of olives, including the Sargano, Carboncella, Ascolana, Coratina, Frantoio, and Moraiolo varieties. An eight-hundred- year- old tree may sound ancient, but it’s practically a sapling in olive oil–making years: olive trees started to grow in the southeastern Mediterranean basin more than six thousand years ago, and they were a major item of trade for the ancient Greeks, Romans, Persians, and Phoenicians throughout the Mediterranean region. These varieties contain the polyphenol molecules oleuropein, demetiloleuropein, andquercetin, with an average polyphenol concentration of around 800 milligrams per kilogram. In addition to harvesting the olives from the ancient trees, Marco uses several strategies to ensure the highest possible polyphenol content in his product. The olives are harvested when they have not fully ripened, when their polyphenol production is at its highest. Harvested olives are stored in airtight steel containers to protect them from oxygen and light. Those made into oil are taken to the local facility where they are cold-pressed just hours after they’re harvested. The fresh oil has a uniquely pungent flavor and fragrance, with an initial almost burning sensation and taste. In addition to its flavor and health benefits, the polyphenols contribute to its superior oxidative stability compared to other edible oils. “…the high polyphenol content of EVOO makes it a medicine produced by nature and refined by human expertise and traditions.” In seeking out the health benefits of the Mediterranean diet, it became clear to me that the high polyphenol content of EVOO makes it a medicine produced by nature and refined by human expertise and traditions. Like any medicine, the precise amount of active ingredients and the quality of processing play major roles in its effectiveness. But unlike FDA approved medications, the production and marketing of EVOO is not controlled, resulting in a variety of brands with many unsupported health claims. So rather than being misled by the dark appearance of many expensive olive oils marketed as EVOOs produced in Italy or Greece, it is worth investigating where and how they were harvested and processed, as well as their average polyphenol content. This may take a bit of investigating, as most producers don’t include information about polyphenol content on their labels. Given the difficulty of tracking down the polyphenol content, the best way for a consumer to determine it is by taste—a pungent flavor is generally a sign of high polyphenol content. Like many healthy things (and all medications), EVOO should be consumed in moderation. It is obviously a calorie dense food, so adding just the right amount to your salads and dishes without adding excess calories is important to get the most health benefits. And don’t forget, the consumption of EVOO should not been viewed in isolation but rather as one important component of a gut and mind healthy lifestyle. Just like taking probiotics or various supplements while consuming the Standard American Diet (SAD), not doing regular physical exercise and going through life without mindfulness is not better for your health than taking a placebo pill, adding expensive olive oil to such an unhealthy lifestyle, wont move the needle towards better health! Adapted from my book, The Gut Immune Connection By Elvira Rostanzo, MSc and Emeran Mayer, MD The global rising of obesity has become a worldwide public health crisis and represents one of the main challenges for prevention policies. In 2017, it has been estimated that over 2.1 billion people, or nearly 30% of the global population, are overweight or obese. Moreover, the obesity rate among US children and adolescents has tripled in the last three decades. It is estimated that 9.6% of children aged 6–11 years and 18.1% of adolescents aged 12–19 years are obese. Obesity is not just a cosmetic problem, but it is also associated with multiple serious comorbidities including type 2 diabetes, metabolic syndrome, cardiovascular disease, as well as an increase in the risk to develop many types of cancer (breast, ovarian, renal, pancreatic among others). “The growing rate of obesity is related to dramatic changes in eating habits, with the widespread adoption of the so-called Western Diet in both high- and low-income countries.” The growing rate of obesity is related to dramatic changes in eating habits, with the widespread adoption of the so-called Western Diet (the US version of this diet is the Standard American Diet or SAD) in both high- and low-income countries. The Western Diet is characterized by a regular intake of ultraprocessed foods (containing additives like emulsifiers and hidden sugars such as high fructose corn syrup), “fast food” products, unhealthy snacks, and sugary soft drinks. Not surprisingly, the consumption of sugary soft drinks and the rate of obesity and type 2 diabetes have risen in parallel. In response to this diet-induced health crisis, the food industry has made a major effort to replace “classic” sugary sweeteners such as sucrose, dextrose, and high-fructose corn syrup with non-nutritive sweeteners (NNS) that can be classified as artificial (saccharin, sucralose, aspartame, acesulfame-K) or natural (stevia, monk fruit and xylitol). At first glance, there are obvious advantages of making this switch, which promises to allow lovers of sweet tasting foods to “have the cake and eat it too”. The main advantages of using NNS (in addition to their low cost) are the fact that some of these substances are either non-absorbable (sucralose), or have such high sweetening power that they can produce the desired sweet taste, without the negative metabolic effects of high sugar absorption. The perception of sweet taste is mediated by so called sweet taste receptors on your tongue, but also throughout the small intestine. As a result, NNS have become popular thanks to their negligible caloric content, and NNS-sweetened products (in particular beverages) are labeled as “zero calories” or “no sugar added”. However, because of the various functions of sugar, removing sugar from food products not only influences sweetness, but can also affect the overall functionality, flavor perception, texture, and overall liking of food. But do NNS really live up to their promises of weight loss, and prevention of glucose intolerance and type 2 diabetes mellitus? Unfortunately, there are conflicting findings reported regarding their effects on body weight control, glucose homeostasis, and underlying biological mechanism. Trying to find an answer may be not so easy. NNS are widely-used and to find people that do not use NNS on a regular basis is challenging, leading to several studies which have been either negative (not showing any benefit) or inconclusive. A recent research study from the research team led by Eran Elinav at the prestigious Weizmann Institute in Tel Aviv published in the journal Cell explored the effect of three of these NNS on glycemic response, and on the human microbiome. The same group of investigators had published results from an earlier study showing that consumption of the three most commonly used NNS — saccharin, sucralose and aspartame — directly induces the development of obesity and glucose intolerance in mice. In this earlier study, the investigators showed that these effects were mediated by changes in the composition and function of the mice’s intestinal microbiota of the mice and that the deleterious metabolic effects could be transferred to germ-free mice by faecal transplantation and were abolished by suppressing the altered microbes in the recipient mice by antibiotic treatment. Demonstrating the translational relevance of these findings for human health, the authors were able to induce changes in the gut microbiome and glucose intolerance by the ingestion of NNS in healthy human subjects. “Two of the tested sweeteners, saccharin and sucralose, significantly elevated the glycemic response during consumption…” The recent study by the Weizmann Institute investigators was conducted on 120 subjects in good metabolic health and lasted 29 days. All the participants were normal weight (according to Body Mass Index, BMI) and had not been consuming any NNS. Two of the tested sweeteners, saccharin and sucralose, significantly elevated the glycemic response during consumption, while neither aspartame nor stevia had a significant effect on glucose tolerance during this time period. These results indicated that short-term consumption of sucralose and saccharin, even in doses lower than the Acceptable Daily Intake, can negatively impact glycemic responses in healthy individuals, and that not all NNS had the same negative effects. “The results of both studies highlighted that NNS are not inert compounds, even when consumed in very small amounts…” Similar to their findings in the 2014 study, all four tested NNS (saccharin, sucralose, aspartame, and stevia) significantly and distinctly altered the human intestinal and oral microbiome, as well as gut microbial metabolites in circulation, impacting the gut microbial ecosystem through several direct and indirect mechanisms. NNS inhibited the growth of some bacteria, while the prevalence of other bacterial species increased in the presence of NNS. Importantly, germfree mice which received microbiomes from human subjects from each of the four NNS-supplemented groups exhibited glycemic responses largely reflecting those noted in the respective human donors. In other words, the specific gut microbial changes induced by saccharin, sucralose, aspartame, and stevia consumption were able to cause similar metabolic changes as seen in the human subjects in the recipient mice. Based on their findings, the authors concluded that human NNS consumption may induce person-specific, microbiome-dependent changes in glucose absorption. The results of both studies highlighted that NNS are not inert compounds, even when consumed in very small amounts, and that such small amounts can produce significant metabolic changes in our body even when the NNS are consumed in doses lower than the Acceptable Daily Intake. One of the reasons for these unexpected, and largely unknown, findings is the role of the gut microbiome. Further studies are needed to better elucidate their effects on human health on long term. NNS have long been used to restrict caloric intake and prevent or reverse obesity; the label “zero calories”, “with natural sweeteners” or “no added sugar” may suggest that these sugar alternatives are better for our health. However, there is no scientific evidence that this is indeed the case. On the contrary, it has been shown that the growing rate of overweight and obesity occurs primarily among children who are most exposed to foods and beverages rich in NNS. Thus, while people with hyperglycemia, type 2 diabetes, or metabolic syndrome have been advised to avoid or limit sugar intake, the recommended alternative to replace sugar with NNS seems to increase the risk to develop the very metabolic disorders that they are thought to prevent. “The extract is 150-250 times sweeter than table sugar, has zero calories and carbs, and does not raise blood glucose levels.” As the recent Suez study showed differences in negative metabolic effects between synthetic NNS and those derived from plants, one may ask if natural NNS like Stevia and monk fruit may be a better alternative to replace sugar. Stevia sweeteners are derived from the leaves of the Stevia rebaudiana plant, an herbal shrub native to South America. This plant has been used for food and medicinal purposes for hundreds of years. Monk fruit, or lo han guo, is a small green melon native to southern China and named after the monks who first cultivated it centuries ago. Monk fruit gets its sweetness from natural compounds called mogrosides, which are also thought to have anti-inflammatory effects. Monk fruit sweetener is made from extract derived from dried fruit. The extract is 150-250 times sweeter than table sugar, has zero calories and carbs, and does not raise blood glucose levels. Its health benefits have been well-known in Traditional Chinese Medicine (TCM) for decades, long before it became a popular topic in the wellness conversation. According to a 2011 study, based on its anti-inflammatory effects, monk fruit has been used in TCM for centuries to make hot drinks that relieve sore throats. Most NNS can cause side effects like gas, bloating, or allergic reactions. Based on the assessment that there are no known side effects of monk fruit sweeteners, the Food and Drug Administration has given monk fruit the label of “generally recognized as safe” (GRAS) for everyone, including pregnant women and children, even in the absence of controlled scientific studies on the effects of long-term use. “Unless specifically stated on the label, one should not assume that all monk fruit products are carb- and sugar-free.” Even though the ingestion of monk fruit is generally safe for those with diabetes (as it doesn’t increase blood sugar levels), foods and drinks sweetened with monk fruit (as well as some monk fruit sweetener blends) may include added sugars and other ingredients that increase calorie counts or affect insulin sensitivity. Unless specifically stated on the label, one should not assume that all monk fruit products are carb- and sugar-free. In conclusion, a growing number of studies have identified negative metabolic effects in response to the ingestion of certain NNS. One of the reasons for these largely unknow negative effects are related to the interaction of these molecules with the gut microbiome which plays a key role in maintaining glucose homeostasis. As shown in these studies, the microbiome can be altered by some NNS and even healthy people can be affected. Based on current evidence, plant-derived NNS like stevia and monk fruit do not have the same metabolic side effects as synthetic compounds, even though definitive clinical evidence remains to be established. By Emeran Mayer, MD and Jill Horn Colorectal cancer (CRC) is a major global health burden as its ranks third in terms of incidence and second in mortality worldwide. It has increased steadily in recent years, including in younger age groups. As with many chronic diseases, it is the interaction between genetic and environmental factors (also referred to as “exposome”) that determines the risk for CRC development and outcome. Environmental risk factors include western dietary habits, smoking, obesity, diabetes, and heavy alcohol consumption, with the gut microbiome playing an important role of mediating between environmental factors, in particular our diet and the development (“carcinogenesis”), formation and progression of CRC. “Scientific evidence has demonstrated associations between CRC prevalence, and the composition and function of the gut microbiota…” The gut microbiome plays an important role in energy homeostasis, keeping the intestinal epithelium intact, protecting against pathogenic organisms, and maintaining a healthy immune system. Emerging evidence has demonstrated associations between CRC prevalence, and the composition and function of the gut microbiota, suggesting a role of the gut microbiome in colorectal carcinogenesis. Much of the focus on microbiome research in CRC has been on microbes as pathogenic drivers of CRC, in the hope that these efforts can be leveraged for preventive, diagnostic, and therapeutic purposes. Human data and data from mechanistic studies in cell culture and animal models support a role of specific microbes as potentiators of tumor development — including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, colibactin-producing Escherichia coli and Peptostreptococcus anaerobius. Chronic low grade immune system activation of the colon also plays an important role the development of dysplasia and CRC. For example, in patients with inflammatory bowel disease, chronic, severe inflammation of the colon increases the likelihood of developing CRC. More subtle inflammation, such as the changes occurring in individuals with metabolic endotoxemia in otherwise healthy colonic tissues plays an important role in the conversion of a healthy colon to one with dysplastic, precancerous lesions. Disruption of the intestinal barrier by inflammatory mediators facilitates bacterial translocation from the intestinal lumen into the gut-associated immune system and into the systemic circulation and, ultimately, exposure of immunogenic microbial compounds to both epithelial cells and antigen-presenting cells. Activation of immune signaling pathways by bacterial stimuli results in a loss of homeostasis that drives an inflammatory environment conducive to the development of colon cancer. The presence of colorectal adenoma, the early stage of CRC, has also been found to be associated with changes in the gut microbiome, raising the possibility of future use of such microbiome changes as biomarkers enabling screening tests and early diagnosis. The changes in the gut microbial ecosystem have been attributed to key dietary factors in the Standard American Diet (SAD), such as low intake of fruits and vegetables, high consumption of animal-based products, and ultra-processed foods. There are multiple mechanisms and pathways through which the gut microbiota can affect CRC formation and progression, including inflammation, tumor-inducing metabolites, genotoxins, and oxidative stress. “Emerging evidence confirms that colorectal cancer and gut microbiome composition and diversity alterations are directly correlated, suggesting a role of the intestinal microbiota in colorectal carcinogenesis”. Based on a number of large epidemiological studies, largely plant-based and vegetarian-style diets such as the traditional Mediterranean diet, with consumption of an abundance and variety of fruits, vegetables, nuts and whole grains, low in red meat, and especially processed meat have been associated with a low risk for developing CRC, and have been recommended as an important component of CRC prevention measures. Even though it remains to be determined, which individual component of the Standard American Diet (SAD) is the main factor underlying the increased prevalence of colon cancer, the high consumption of red meat and dairy products has been implicated as potential risk factor in a number of studies. However, a recent meta-analysis published in the prestigious journal Nature Medicine of epidemiological studies on the association of unprocessed red meat consumption and several health outcomes, including CRC, failed to show a significant correlation. Regardless of the causative role of red meat in colon carcinogenesis, the more colorful the meals, the better, as the plant compounds responsible for the various colors of vegetables and fruit which often belong to the polyphenol group have been shown to have beneficial effects on the gut microbiome, and may reduce the risk for the development of colon cancer. Altogether, diets made up to 75% of fruits and vegetables and low in animal products are the most recommended for protection from CRC. “…one would expect that dietary assessment and nutrition counseling would be an integral part of CRC prevention programs.” In view of the close relationship between diet, the gut microbiome and CRC risk, one would expect that dietary assessment and nutrition counseling would be an integral part of CRC prevention programs. This relationship may be one of the drivers of increasing CRC risk in younger age groups, which has resulted in lowering of the recommended age for colon cancer screening, but not in increased efforts in dietary counseling. Such efforts are nearly absent in gastroenterology practices with large numbers of colon cancer screening, and the topic of diet has largely been absent in the recent discussions about the most cost-effective approaches to colon cancer screening. In the absence of satisfactory medical therapies for irritable bowel syndrome (IBS) and other disorders of brain gut interactions, clinical guidelines identify self-management as a first line treatment. Its goal is for patients to acquire skills to help reduce the impact of their condition, optimize function, and, in the absence of curative therapy, gain optimal control of symptoms. Behavioral self-management modalities typically emphasize a strategy called cognitive behavioral therapy (CBT). CBT is a learning-based treatment that teaches practical skills for unlearning symptom-aggravating processes such as symptom related worry and avoidance, substituting more adaptive self-management skills. In a collaborative study with Dr. Jeff Lackner from the University of Buffalo, NY, we aimed to test the hypothesis that CBT-treated patients with IBS who learn to self-manage painful gut symptoms show improvement in cognitive flexibility, abdominal pain, and quality of life. Participants included 130 patients with a mean age of 40 years and with moderate-to-severe symptoms who were randomly assigned to either CBT (N = 86) or a nonspecific education/support (EDU) intervention (N = 44). CBT but not EDU patients showed significant symptom improvement from baseline to post-treatment in cognitive flexibility. For CBT patients, changes in cognitive flexibility were significantly associated with changes in IBS symptom severity, abdominal pain, and IBS QOL. IBS subjects whose symptoms improved on CBT, also showed distinct changes in brain network connectivity and in the gut microbiome.The ability to self-manage painful IBS symptoms refractory to conventional medical and dietary treatments is related to the ability to respond flexibly across shifting contexts using cognitive change procedures featured in CBT for IBS. For the majority of people that read the news last week that the iconic founder and owner of the world-famous company Patagonia had given his company away, it came as a shock, unparalleled in its scope and details in the business world. According to the New York Times, Mr. Chouinard, his wife and two adult children have transferred their ownership of Patagonia, valued at about $3 billion, to a specially designed trust and a nonprofit organization. They were created to preserve the company’s independence and ensure that all of its profits — some $100 million a year — are used to combat climate change and protect undeveloped land around the globe. However, for anybody who has known this self-declared reluctant billionaire, this decision wasn’t amazing at all. It was simply the realization of a lifelong dream. I first met Chouinard in 2018. Together with my wife and son, and a small film crew I had the privilege to do an interview with him about his company Patagonia Provisions, at his modest but beautifully located home in Jackson Hole, Wyoming. We sat in the meadow in front of his house with a breathtaking view of the snow-covered Teton mountain range, and Chouinard spoke both plainly and eloquently about his beliefs and about the state of food production in the US. “There’s nothing wrong with this planet, it’s perfect, but we’re destroying it of course,” he said. “Still, all of the answers are in nature. I think I’ve always believed that.” Looking back at the 3 hourlong interview, it seemed Mr. Chouinard had plans for quite some time to find a solution that would reconcile seemingly incompatible aspects of his life: his unconditional love for nature and the outdoors, his serious and growing concerns about climate change, his self-identification as a socialist and his phenomenal success as a businessman. For many afficionados of Patagonia, it may be news that Chouinard has been passionate about transforming the current model of industrial agriculture to a regenerative organic one, helping to tap the solutions already held in nature. “Regenerative organic farming practices yield large crops while building healthier soil, which can draw down and store more greenhouse gases,” he set forth in a recent essay on the subject. “Free-roaming buffalo restore prairie grasslands, one of Earth’s great carbon storage systems. Rope-cultivated mussels produce delicious protein while cleaning the water where they’re grown. Place-based and selective-harvest fishing techniques allow us to target truly sustainable fish populations without harming less abundant species. As these examples illustrate, the more we roll up our sleeves and dig into the world of food, the more we discover that the best ways are often the old ways.” Chouinard was as fluent—and adamant—about his mission in our discussion as well, articulating his vision for pioneering a new way of addressing our health and our environment by changing the way that we grow our food. “That’s the revolution I want to be a part of,” he said decisively. It may sound unusual to hear the word “revolution” from someone who is a giant in the business world and listed as a billionaire in the Forbes ranking (a listing he apparently is not happy about). But then Chouinard is an unusual leader and, in his own words, a “reluctant businessman”—the title of his most recent book: Let My People Go Surfing: The Education of a Reluctant Businessman — who is not afraid to blaze a path all his own. (Among other enlightened company policies, he has instituted at Patagonia, Chouinard has decreed that when the surf is up, employees should drop their work and go surfing. “I don’t care when you work,” he clarified, “as long as you get the job done.”) Indeed, he sees himself more as a socialist than a capitalist, and has always pursued what seems morally right and important to him as opposed to what made the most profit for his company. One of his favorite quotes is: “If you want to understand entrepreneurs, study the juvenile delinquent.” Because “the juvenile is saying with his actions, ‘This sucks, I am going to do my own thing,’” he explained, “That’s what the entrepreneur does. They just say, ‘This is wrong, I am going to do it this other way’ . . . I love breaking the rules.” Here are a few more of Yvon’s remarkable statements from the 2018 interview. In response to my question about the basis of his business, he responded: “My business is based on having a wild nature, you know, free flowing rivers and snow in the mountains … and public lands. … I feel like I have more responsibility to protect those places than your average business” “I’m basically a socialist and my company is a socialistic organization. .. ” And in response to my question about the mission of his business: “If you were going to ask me today why I’m in business, in fact I’m going to change my mission statement. My mission statement is going to be we’re in business to protect our home planet.” For Yvon in his early 80s, this is not just a dream, and he has done a lot to make this vision become a reality and reverse the destructive course of our current food system. He has a natural talent for building a team of people and followers that devotedly believe in Patagonia’s core principles and who will bring his vision forward into the future. Chouinard has also ensured that his mission will be widely carried out by, in 1985, creating a program at Patagonia that has since offered more than $100 million in grants to grass roots organizations and innovative startups that are forging new methods of food production in a responsible, regenerative organic way. Among many other projects, Chouinard has also supported the development of the perennial long root grain Kernza and turned it into several specialty beers, such as Patagonia Long Root Ale; he promotes the consumption of sustainably and humanely harvested salmon and bison meat; and he leads many educational and marketing campaigns, including producing impactful documentaries about environmental issues such as “Dam Nation” and “Artifishal.” The encounter with this unique human being 4 years ago, which I documented in detail in my book, The Gut Immune Connection and which I plan to incorporate in the upcoming documentary, Interconnected Planet, had a long-lasting influence on my own world view and career trajectory. Even though other billionaires, including Jeff Bezos, Laurene Powell Jobs, the widow of the Apple co-founder Steve Jobs, Mike Bloomberg, Mark Zuckerberg, and Bill Gates have joined the exclusive club of climate philanthropists, Chouinard has set the gold standard of what needs to be done to save the planet from pending climate doom. Let’s hope other companies will follow his lead. Parts of this post have been taken from my book, The Gut Immune Connection. While there has been an explosion of public interest in the topics of gut health, gut healthy foods and supplements in the past couple of years, the intricate link between food, human health, and the health of the planet, the so called One Health concept has received considerably less attention. In 2019, one of the most comprehensive reports based on the One Health concept—exploring the intricate connections among a healthy diet, sustainable food systems, and planetary health—was published in the Lancet by the EAT-Lancet Commission, a group of thirty-seven leading scientists from various disciplines and sixteen countries, co-chaired by Johan Rockstroem, from the Potsdam Institute for Climate Impact Research, and Walter C. Willett from the Harvard T. H. Chan School of Public Health. When I interviewed Willett for my book, The Gut Immune Connection, he explained “This commission was put together . . . to look at the issue of whether and how we would be able to feed a diet that is both healthy and sustainable to about ten billion people by 2050.” The findings, according to its authors, “provide the first ever scientific target” for reaching this goal. The commission reported that the production and consumption of food in the Anthropocene—our current age, in which human activity has been the primary influence on climate and the environment—represents one of the greatest health and environmental challenges of the twenty-first century. This is not only because the world is dealing with an epidemic of chronic noncommunicable diseases related to obesity, metabolic disorders, cardiovascular diseases, and chronic brain disorder, but also because many environmental systems and processes have been pushed beyond safe boundaries. Disturbances in food supply and consumption have resulted in 2.1 billion adults being overweight or obese and in a doubling of the global prevalence of diabetes in the past thirty years—while at the same time more than 820 million people are undernourished, 151 million children are stunted, 51 million children suffer acute malnutrition, and more than 2 billion people are micronutrient deficient. Meanwhile, food production is the largest cause of global environmental change. Agriculture occupies about 40 percent of land around the world, and food production is responsible for up to 30 percent of greenhouse-gas emissions. It also absorbs 70 percent of our freshwater use. Experiencing the historic drought conditions in California combined with continuously rising temperatures in real time, turns these statistical numbers into daily experiences for millions of people. To eat both healthily and sustainably, the EAT-Lancet Commission recommended a “win-win” diet, meaning there must be a safe “operating space” for food systems, defined by how much we need of specific food groups daily in order to both maintain human health and the environment—for example, one hundred to three hundred grams (three and a half to seven ounces) of fruit per day. Willett explained: “We have a lot of evidence for what a healthy diet is. If we look just at health, it points us in the direction of being largely plant-based— not necessarily all vegetarian or vegan but predominantly plant-based. Remarkably, the convergence of scientific advances in a wide range of disciplines, ranging from epidemiology, the microbiome field, metabolism, neuroscience, all the way to plant and soil science, all support the benefits of [this] diet as well.” A recent study, published in the prestigious journal Proceedings of the National Academcy of Sciences (PNAS) a group of investigators from the University of Oxford, UK, under the leadership of Michael Clark aimed to increase the understanding of the environmental impacts of commercially available food products in order to support transitions to environmentally sustainable food systems. Using ingredient lists to infer the composition of each ingredient in commercially available foods and pairing them with environmental databases containing information about environmental impact they derived estimates of a food product’s environmental impact across four indicators: greenhouse gas emissions, land use, water stress, and eutrophication potential (harmful algal blooms, dead zones, and fish kills secondary to agricultural run off into rivers and coastal waters). Using this approach on 57,000 (!) food products commercially available online from eight online stores, including the UK based company called Tesco showed that certain food categories can be identified that have low (e.g., sugary beverages, fruits, breads), to intermediate (e.g., many desserts, pastries), to high environmental impacts (e.g., red meat, fish, cheese). They could also show that more nutritious products are often but not always more environmentally sustainable. They identified exceptions to this trend, with foods consumers may view as substitutable can have markedly different impacts. The authors reported that “…many Aisles at Tesco were win-wins (good for the environment and good for human health) and were more nutritious and sustainable than most other Aisles (e.g., an estimated environmental and nutritional impact below the median of all of the Aisles examined). These Aisles included, for instance, fruits, vegetables, salad, breakfast cereals, some breads, and meat alternatives (e.g., tofu, vegan sausages). Conversely, there were numerous lose-lose foods (bad for the environment and bad for human health) with nutrition and environmental impacts above the median. These foods included cheese, chocolate, savory pies, and quiches. Win-lose foods (good nutrition composition but above median estimated environmental impact) included fish and seafood, (threatened by overfishing) nuts (excessive water use), and some ready meals. Interestingly, beef and lamb also fell into the win-lose category. According to the authors (not necessarily shared by myself), “…evidence suggests that the health and nutrition impacts of beef can range from detrimental to beneficial, depending on the context in which it is consumed: studies in high-income and high-consuming contexts indicate that increasing consumption of red meat would negatively affect health outcomes, whereas red meat consumption (and, more broadly, animal-based foods) in food-insecure contexts can be integral to nutrition security. Lose-win categories (poor nutrition quality but below median environmental impacts) included sweet cakes and pies, sugary drinks (colas, squash, cordials, fruit juices), frozen desserts, and table sauces. Many of these lose-win categories included processed food products that contain ingredients with low environmental impacts but that are also In summary, the Clark study using a more granular analysis supported many of the conclusions reached by the EAT Lancet commission 3 years ago, pointing out the complexity of dietary recommendations. By estimating the environmental impacts of food products in a standardized way, the authors aimed to enable informed decision making by end users such as consumers and policy makers. For the average consumer, the message is clear for the win-win category of foods, which corresponds with the general recommendations of a largely plant-based diet, and for the win-lose category which highlights the negative environmental impact of several healthy foods. The question remains if the findings of these amazing research efforts will be able to transform dietary habits of consumers in industrialized countries, in particular in the US soon enough to slow or prevent the detrimental effects on the health of humans and the planet. Parts of this post were taken from chapter 9, The One Health Concept of The Gut Immune Connection. For most people chronic stress has become a regular aspect of modern life, amplified by a bombardment with negative news from the internet: the pandemic, catastrophic climate events, political polarization, and a raging war in the middle of Europe are just the most recent examples. As I will explain, our biology is poorly equipped to deal with this type of constant and repeated exposure to stress 24 hours a day. The mismatch between our ancient biological acute stress response systems and this new form of chronic perturbation of the body’s homeostasis is likely to negatively affect our health. Acute, often life-threatening stress has been part of human life for millions of years and there has been enough time in our evolutionary history to perfect our biological stress response systems in a way that has kept our species alive through natural disasters, wars, famines, and pandemics. There are two such systems in our body: the older immune stress response system and the brain’s stress response system, and both are often engaged together. Our organism responds to any situation – in the presence or the future – that is perceived as a threat to our integrity and homeostasis by engaging one or both of these stress response systems. While they have evolved and are optimized to respond to infrequent, but life-threatening stresses – the poisonous snake, the wild tiger, the severe injury, or the infection, for most people in developed countries, these are no longer the kind of stresses we encounter on a regular basis. Unfortunately, the worry about being shot remains a persistent stress for a significant segment of the population as highlighted by the series of recent high profile police shootings. Today’s perturbation of our body’s balance most often comes in form of chronic stressors associated with modern life: The chronic psychological stress on our minds generated by the relentless daily bombardment with negative news, worries about the future, increasing competition, and number of challenges associated with a lower socioeconomic status (in plain language, poverty, food insecurity, health conditions). And at the same time, the dietary stress on our metabolism in form of the unhealthy Standard American Diet (SAD). Unfortunately, these two types of stressors often occur together, and the relentless engagement of our stress systems comes at an increasing cost to the health of our bodies and minds. Evolution had not foreseen these kinds of stressors which we have never experienced as a species. While our stress response systems (the sympathetic nervous system and the HPA axis) keep responding in the same way that has been so adaptive for human life, chronic hyperproduction of the stress mediator’s cortisol and noradrenaline, and chronic systemic engagement of the immune system are responsible for many aspects of our current chronic non-infectious disease epidemic as I have described in detail in The Gut Immune Connection. Not everybody responds to these challenges in the same way: the responsiveness of our neurological and immunological stress system is influenced by genetic factors and is programmed during the first 18 years of life, starting in utero, and will determine our lifetime risks for developing these common chronic diseases. This will result in a situation where two people exposed to the same kind and severity of stress will respond in very different ways: one will remain healthy, the other one developing a chronic disease. In this short videoclip, I provide a brief explanation of the relentless transition that has been occurring in the US and increasingly in developing countries from a state of optimal health and the associated subjective feeling of wellness to the current epidemic of chronic non-infectious diseases and provide an understanding of how both psychosocial and dietary stresses interact to result in a maladaptive engagement of the stress systems ultimately leading to organ dysfunction and disease. If you want to learn more about this topic, you might also be interested in my book, The Gut Immune Connection, which is available now. When I spent time in Seoul, South Korea, I had the pleasure of experiencing traditional Korean meals with a wide variety of different fermented vegetables and seafood. I have always wondered if this unique eating habit of Koreans is reflected in different health outcomes when compared to the Standard American Diet (SAD). A recent study has shown that consumption of a large variety of fermented foods is associated with an increased diversity of the microbial ecosystem in our gut, even more so than the diversity associated with a diet rich in fiber. Even more surprising was the observation that a lot of the new microbial taxa that appeared in the fermented food consuming group were not contained in these fermented foods, but were recruited from another source. Does this observation obtained under controlled conditions in a small group of healthy people translate into health benefits in a larger population? Dietary habits and health outcomes in South Korea may hold an answer to this question. Since Koreans have a high consumption of fermented food from early on in life, do adult Koreans have a more diverse microbiome than people living in the US? And if they do, is this diversity associated with measurable health benefits such as lower rates of cancer and cognitive decline? Dramatic dietary changes associated with the adoption of the SAD in Korea (increased consumption of animal products, reduced consumption of plant based and fermented foods), which were associated with the migration of people from rural areas to big cities, makes this question difficult to answer. The scientific numbers from the Korean natural experiment don’t support such a connection between a diet high in fermented food and the prevalence of cognitive decline. In a 2021 study published in the Journal of Clinical Neurology, researchers found that the prevalence of dementia per 100,000 increased from 178.11 in 2003 to 5,319.01 in 2015 – a dramatic increase! In addition, the standardized prevalence of dementia was higher in other areas than in Seoul metropolitan area, arguing against the rural to metropolitan change in diet hypothesis. Similarly, South Korea has experienced a rapid increase in colorectal cancer incidence rates, making it the country with the second highest incidence rate of colon cancer in 2018, worldwide. Are other factors in the modern Korean lifestyle and eating habits such strong risk factors for neurodegenerative disease and cancer that the consumption of high amounts of fermented foods are unable to compensate for the increased risks? Is the current enthusiasm for the consumption of fermented foods following the Sonnenburg study overblown and not supported by large epidemiological data? Are there particular fermented food items, like fermented dairy products that provide greater health benefits, while most of the fermented foods in the Korean diet (largely plant based and seafood) have less significant effect on these outcomes? Future studies will have to address these questions. So, while eating a variety of fermented food is delicious, the epidemiological studies in the Korean population suggest that they do not necessarily translate into dramatic health benefits, or protection against serious noninfectious diseases, in particular chronic diseases related to low grade immune activation. “In 2021, people in the US spent an estimated $50 billion on dietary supplements and the dietary supplement industry spent about $900 million on marketing” Billions of dollars are being spent by consumers each year on products marketed as health promoting without solid evidence supporting such claims. In contrast to pharmacological treatments which have to be FDA approved before they can be sold to patients (even if they bit the placebo by less than 10%), these unregulated products only have to be safe and can’t make any claims about effectiveness in the treatment of a particular disease. Some of the best-known examples are gluten-free products (annual 8 billion US $ market), probiotics (62 billion), and an incredible array of supplements, including vitamins. More than half of adults take dietary supplements, and use of supplements in the US is projected to increase. In 2021, people in the US spent an estimated $50 billion on dietary supplements and the dietary supplement industry spent about $900 million on marketing. These marketing messages (and messengers) have flourished in the social media, and even the medical establishment has adopted some of the largely unfounded recommendations. Cleverly disguised promotions by internet influencers have become one of the most popular ways of fueling the supplement market and selling supplements has become a lucrative income stream for both physicians and allopathic healthcare providers. “In theory, vitamins, minerals and phytochemicals have antioxidative and anti-inflammatory effects that should translate into a reduction of cardiovascular disease and cancer…” As pointed out by Dr F. Perry Wilson of the Yale School of Medicine in a commentary in the online publication Medscape, the appeal of supplements is obvious. In theory (at least in the test tubes and animal models), vitamins, minerals and phytochemicals have antioxidative and anti-inflammatory effects that should translate into a reduction of cardiovascular disease and cancer, which has remained an elusive goal to reach. However, arguments can be made about the benefits of taking supplementary vitamins in otherwise healthy people. For example, it is well established in the literature that individuals with vitamin deficiencies are at higher risk for bad health outcomes. Even people with lower levels of certain vitamins, not in the deficiency range, are at higher risk for cancer and cardiovascular disease. On the other hand, as I have discussed extensively in The Gut Immune Connection, eating a largely plant based diet, like the traditional Mediterranean, the MIND, and the DASH diets, with lots of fruits and vegetables has repeatedly shown to be associated with decreased cardiovascular disease and cancer risk in large epidemiological studies and in some clinical trials. In order to generate a profit over and above selling these healthy food items, it is reasonable to think that key vitamins, botanicals, and minerals could be extracted from fruits and vegetables, packaged into a pill, and people could avoid the difficulty and expense of maintaining a balanced diet. This is the logic of a large number of health-conscious people who are not willing to abandon the traditional Standard American Diet (SAD) devoid of sufficient amounts of plant-based foods, and rather pop their supplement pills every morning. “Micronutrients in isolation may act in a combinatorial manner and affect the body differently than when naturally packaged with a host of other dietary components” As pointed out by Dr. Jenny Jia in an editorial published in the Journal of the American Medical Association (JAMA) entitled Multivitamins and Supplements—Benign Prevention or Potentially Harmful Distraction, the most common reason people report taking supplements is to improve or maintain overall health. However, in contrast to a single ingredient supplement pill, whole fruits and vegetables contain a mixture of vitamins, phytochemicals, fiber, and other nutrients that probably act synergistically to deliver health benefits. There are thousands of phytochemicals contained in different combinations in fruits and vegetables, and the same concept applies to fiber. Micronutrients in isolation may act in a combinatorial manner and affect the body differently than when naturally packaged with a host of other dietary components. “…current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements, single supplements, or most paired supplements for the prevention of cardiovascular disease or cancer.” In a rare event, two recent large-scale studies have provided evidence-based information related to health benefits of regular vitamin intake. For otherwise healthy, nonpregnant adults, the US Preventive Services Task Force (USPSTF) has updated its recommendation about the use of supplements to prevent cardiovascular disease or cancer. The USPSTF is an independent panel of experts involved in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services. This updated recommendation is based on a new evidence report and systematic review of 84 studies, including 52 new studies since the last USPSTF recommendation on this topic in 2014. It is worth mentioning that these were general-population studies, not studies of people with known vitamin deficiencies. The USPSTF concluded that the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements, single supplements, or most paired supplements for the prevention of cardiovascular disease or cancer. No analyses of individual vitamins — beta-carotene, vitamin A, vitamin E, vitamin D (with a whopping 32 randomized trials), and calcium supplements — showed significant benefit in terms of either cardiovascular disease or cancer. Notable findings for the harm analysis included evidence that vitamin A use might increase the risk for hip fracture, that vitamin E use might increase the risk for hemorrhagic stroke, and that vitamin C or calcium use might increase the risk for kidney stones. As correctly commented by Dr Wilson in the Medscape article, “why are the observational data that show lower vitamin levels linked to worse healthy outcomes so powerful, and the randomized trial data of vitamin supplementation so weak? This is classic confounding. Basically, healthier people have higher vitamin levels, and healthier people have less cardiovascular disease and cancer. Vitamin levels are a marker of overall health, not a driver of overall health.” “…the results of the Harvard study failed to show a significant effect of a daily MVM on breast or colorectal cancer, prostate cancer or melanoma …” Howard D Sesso and collaborators from the COSMOS Research Group at the Division of Preventive Medicine, Brigham and Women’s Hospital and Department of Epidemiology, and the Harvard T.H. Chan School of Public Health, both at the Harvard Medical School published results from another, large randomized, double-blind, placebo controlled clinical trial, evaluating the benefits of daily consumption of multivitamins for the prevention of cancer and cardiovascular disease. The study population included 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y) free of major cardiovascular disease at the time of study begin and recently diagnosed cancer. The intervention phase was from June 2015 through December 2020. Participants were randomly assigned to daily multivitamin multimineral (MVM) supplement or placebo. The primary outcome was total invasive cancer, (excluding non-melanoma skin cancer). Secondary outcomes included major site-specific cancers, total cardiovascular disease, all-cause mortality, and total cancer risk among those with a baseline history of cancer. Consistent with the results of the USPSTF analysis of a large number of published studies, the results of the Harvard study failed to show a significant effect of a daily MVM on breast or colorectal cancer, prostate cancer or melanoma but showed a protective effect on lung cancer. The study did not show a significant association between MVM use and all-cause mortality or mortality from cardiovascular disease. Based on their results, the authors concluded that a daily MVM supplement, compared with placebo, did not significantly reduce the incidence of total cancer or cardiovascular disease among older men and women. The take home message from these two studies is that unless you have a proven vitamin deficiency, or don’t have access to a variety of fresh fruit and vegetables for financial or geographical reasons, you should not expect a health benefit from taking your daily vitamin cocktail for common forms of cancer and for cardiovascular disease. If you get non-specific benefits from the regular MVM, such as higher energy, less brain fog or improved immune function, these benefits may be attributed to the placebo effect, so masterfully orchestrated by your brain. Fecal Microbiota Transplantation (FMT) is a therapy in which fecal material from a single (or multiple) healthy donor(s) is transferred to a diseased individual to restore health. The technique was first described in the 4th Century in China, practiced since the 1950’s and re-discovered relatively recently. Different delivery techniques of the fecal material have been used using enemas and oral applications in capsule form. In a recent article in the Microbiome Times, Luis Gosalbez discussed the current status of this intriguing therapeutic modality. FMT was the therapeutic strategy that sparked considerable interest in microbiome drug development back in 2013, with the publication of the results of a human trial in which FMT was shown to be highly efficacious in the treatment of recurrent Clostridium difficile (C. difficile) colitis, a serious condition affecting the large intestine. C. difficile colitis results when the normal microbial ecosystem in the colon is severely disrupted, a situation generally induced by the intake of antibiotics in vulnerable individuals. Characteristic symptoms include diarrhea, belly pain, and fever. The disease can cause severe damage to the colon and can even be fatal. Its prevalence has been increasing and affects about 200,000 individuals per year. Paradoxically, even though antibiotics are the most common cause of the disease, the most common treatment includes antibiotics, even though recurrence rates with this approach are high, and scientists have tried to find a more effective and long-lasting therapeutic modality. Multiple research groups and companies have been involved in the development and evaluation of FMT treatments for different conditions, including C. difficile infection, irritable bowel syndrome, inflammatory bowel diseases, autism spectrum disorder and metabolic syndrome. Despite some promising results in some studies, results have been conflicting and largely disappointing, and the dramatic benefits seen in the treatment of C. difficile could not be demonstrated in other disease areas, raising fundamental questions about the usefulness of this approach for disorders other than C. difficile. Initially, FMT was performed after little processing of the original fecal material. However, advances in microbiome science have allowed to identify the key microbial species or activities thought to be responsible for its efficacy. At the same time, safety concerns, such as transmission of enteric infections, or induction of metabolic and psychiatric disorders (as has been observed in animal models) have also made it necessary to design processes which eliminate or rule out the presence of infectious agents, donors with psychiatric disorders, or microbial metabolites with potential systemic effects. Whereas some current FMTs are still the result of simple processing (e.g., filtration, centrifugation), some companies have designed sophisticated procedures to further refine the original material, creating products composed of defined consortia of microorganisms. A logical step in the search to develop gut microbiome-based therapeutics was to replace the actual stool transplantation with transfer of gut microbial communities (or consortia), or by the metabolites produced by these consortia. Drugs based on FMT-derived defined consortia of microorganisms are amongst the most advanced clinical programs of the entire microbiome drug development industry. In 2021, two leading companies, namely Seres Therapeutics and Rebiotix-Ferring Pharmaceuticals, reported positive results from their respective Phase 3 clinical trials in recurrent C. difficile infection using microbial consortia, and this month, Seres announced further confirmatory results from an additional study with their lead candidate for this indication. Both companies are now involved in the process of approval to become the first FDA-authorized microbiome therapeutic for C. difficile. Whereas infectious diseases (primarily recurrent C. difficile) have classically been the main application of FMT, oncology indications have been gaining significant traction over the last years. The exploration of the therapeutic benefit of FMT in cancer patients started with applications in supportive care as a means to preserve or restore the gut microbial ecosystem damaged or impoverished after cancer treatments, for instance aiming at preventing colitis and chemotherapy-induced diarrhea. These applications have followed a mechanistic rationale somehow similar to the one of FMT in C. difficile. However, after it became clear that the gut microbiome plays an important role in mediating and predicting the benefits of some cancer treatments, in particular immunotherapy-based approaches, efforts have started to explore FMT as an adjuvant therapy to immunotherapy in the treatment of melanoma, leukemia and other malignancies. Given its potential immune-modulatory capacity, also a large share of FMT research programs have focused on immune-mediated diseases, mostly Inflammatory Bowel Disease. In summary, based on available clinical data from high quality clinical trials, several questions about the clinical benefits of FMT and its more commercial variants can be addressed: Extra-virgin olive oil (EVOO) has become a popular component of gut and brain healthy recipes. EVOO not only adds a delicious flavor to your salad and vegetables, but its health benefits have been reported from preclinical and clinical studies. EVOO is one of the key health-promoting ingredients of the Mediterranean diet. These benefits are applicable to a wide range of metabolic disorders and cardiovascular diseases. “…current evidence suggests benefits are largely related to polyphenols and vitamin antioxidants—vitamins A and E—found in the oil.” There are at least two major components that mediate the oil’s health benefit—the high concentration of monounsaturated fatty acids (primarily oleic acid) and the high content of polyphenols (primarily oleuropein and hydroxytyrosol). As explained many times in this blog, polyphenols exert their health benefit with the help of the gut microbiome, and research suggests this may be true for oleic acids, too. Oleic acid is the predominant fatty acid in olive oil—73 percent of its total oil content—while 11 percent is polyunsaturated, such as omega-6 and omega-3 fatty acids. Monounsaturated fatty acids (MUFAs) are quite resistant to high heat, making EVOO a healthy choice for cooking. Traditionally, the high content of MUFAs was considered to be responsible for the protective effects of EVOO, but current evidence suggests benefits are largely related to polyphenols and vitamin antioxidants—vitamins A and E—found in the oil. “…the concentration of polyphenols in EVOO ranges from 50 to 800 milligrams per kilogram…” As many as thirty different polyphenol molecules have been identified in different olives. Furthermore, the concentration of polyphenols in EVOO ranges from 50 to 800 milligrams per kilogram, and the amount of polyphenols in EVOO depends on the region where the olives were grown, corresponding differences in climate, soil composition, degree of ripeness when harvested, and the oil-extraction process. In addition, the phenolic fraction of olive oil can vary greatly among different types of olives. As a result, it can be a challenge to figure out which olive oil to buy in order to get the full benefit in terms of both flavor and polyphenols. “…olive trees started to grow in the southeastern Mediterranean basin more than six thousand years ago…” I learned more about olive oil a couple of years ago, when I visited my friend Marco Cavalieri, the owner of Le Corti Dei Farfensi in Fermo, on the picturesque Adriatic coast of Italy. In addition to his wines, Marco produces EVOO from eight-hundred- year- old olive trees, using a wide variety of olives, including the Sargano, Carboncella, Ascolana, Coratina, Frantoio, and Moraiolo varieties. An eight-hundred- year- old tree may sound ancient, but it’s practically a sapling in olive oil–making years: olive trees started to grow in the southeastern Mediterranean basin more than six thousand years ago, and they were a major item of trade for the ancient Greeks, Romans, Persians, and Phoenicians throughout the Mediterranean region. These varieties contain the polyphenol molecules oleuropein, demetiloleuropein, andquercetin, with an average polyphenol concentration of around 800 milligrams per kilogram. In addition to harvesting the olives from the ancient trees, Marco uses several strategies to ensure the highest possible polyphenol content in his product. The olives are harvested when they have not fully ripened, when their polyphenol production is at its highest. Harvested olives are stored in airtight steel containers to protect them from oxygen and light. Those made into oil are taken to the local facility where they are cold-pressed just hours after they’re harvested. The fresh oil has a uniquely pungent flavor and fragrance, with an initial almost burning sensation and taste. In addition to its flavor and health benefits, the polyphenols contribute to its superior oxidative stability compared to other edible oils. “…the high polyphenol content of EVOO makes it a medicine produced by nature and refined by human expertise and traditions.” In seeking out the health benefits of the Mediterranean diet, it became clear to me that the high polyphenol content of EVOO makes it a medicine produced by nature and refined by human expertise and traditions. Like any medicine, the precise amount of active ingredients and the quality of processing play major roles in its effectiveness. So rather than being misled by the dark appearance of many expensive olive oils marketed as EVOOs produced in Italy or Greece, it is worth investigating where and how they were harvested and processed, as well as their average polyphenol content. This may take a bit of investigating, as most producers don’t include information about polyphenol content on their labels. Given the difficulty of tracking down the polyphenol content, the best way for a consumer to determine it is by taste—a pungent flavor is generally a sign of high polyphenol content. Like many healthy things (and all medications), EVOO should be consumed in moderation. It is obviously a calorie dense food, so adding just the right amount to your salads and dishes without adding excess calories is important to get the most health benefits. Taken from The Gut Immune Connection with minor edits What is responsible for the multiple benefits of a largely plant based diet? The benefits of a largely plant-based diet have been implicated in primary disease prevention, disease-risk reduction, as well as healthy aging. The most well known example of a largely plant-based diet is the traditional Mediterranean diet. A series of observational and epidemiological studies have concluded that higher adherence to this type of diet is positively associated with better cognitive function and reduced risk of several chronic often comorbid diseases, including cardiovascular disease, depression, Parkinson’s, and Alzheimer’s disease. The regular consumption of a Mediterranean diet has also been shown to be associated with reduced microvascular brain damage. This suggests a possible role of diet-related impairments in cerebral blood flow to brain regions involved in different aspects of memory such as the hippocampus and the prefrontal cortex. Several variants of the Mediterranean diet such as the DASH diet (Dietary Approaches to Stop Hypertension) and the MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) have been shown to reduce several cardiovascular risk factors, and are associated with better cognitive function, slower cognitive decline, lower depressive symptoms, decreased risk of dementia and larger total brain volumes. In summary, these epidemiological studies strongly suggest benefits of these largely plant-based dietary patterns both on brain and cardiovascular health, with considerable evidence for a mediating role of improvements in cerebral vascular function. The unique family of polyphenol molecules. Polyphenols are bioactive compounds (referred to as “bioactives”, “phytochemicals” or “botanicals) found in plants, consisting of a large, diverse group of molecules, serving two major beneficial roles in plants: One, as defense mechanisms to respond to perturbations of homeostasis, such as drought, UV light, pests, and diseases and two as part of a signaling code between soil microbes living in close proximity of the root system and the plant. While many polyphenols are natural antioxidants when evaluated in a test tube, able to scavenge harmful free radicals that would otherwise damage the cell, only a very small proportion of their beneficial effects when ingested by humans is related to their antioxidant effects. Polyphenols are found in fruits and vegetables, with tea, pome fruits and some berries being among the foods richest in polyphenols. More than 8,000 polyphenol compounds have been discovered in various plant species, which can be classified into four subclasses: phenolic acids (~30% of all polyphenols), stilbenes, lignans, and flavonoids (~60% of all polyphenols). Flavonoids, the largest family of polyphenols, can be broken down into 6 further subclasses: flavanols (also known as flavan-3-ols), flavonols, flavanones, flavones, anthocyanins, and isoflavones. Bioavailability studies in humans indicate that due to their large size, flavonoid polyphenols are poorly absorbed in the small intestine (5-10%), reaching very low, transient plasma levels after consumption. This lack of bioavailability has led the FDA several years ago to remove a comprehensive website listing polyphenols based on their antioxidant capacity. (Antioxidant capacity is the ability for a compound or compounds to reduce the concentration of free radicals in a given system, a test almost exclusively determined in an in vitro system). This assessment is very different from what happens to these molecules when consumed by a person. Most of polyphenols will reach the ileum and colon intact where they interact with the gut microbiota resulting in an extensive chemical modification of the ingested compound into small phenolic, absorbable metabolites “…beneficial effects of polyphenol consumption on brain and cardiovascular health have been supported by a growing number of randomized controlled trials…” Even though epidemiological studies demonstrating a beneficial effect of polyphenol consumption on brain and cardiovascular health have been supported by a growing number of randomized controlled trials, conflicting results have been reported, with considerable divergence in study designs and poor characterization of the tested products (e.g., whole fruit powders, polyphenol-rich berry extract, fruit juices, effect of extensive processing of the original compound), impeding the progress to conclusively demonstrate a causative role of polyphenol containing foods on brain health. The idea that dietary bioactives, food constituents not essential to human life, may play an important role in disease risk reduction, primary disease prevention, and healthy aging, has had significant developments in the last decade. For example, there are a considerable number of dietary intervention studies which found that the flavanol epicatechin (contained in green tea, red wine, and cocoa beans) plays a role in the prevention of cardiovascular disease, as well as the secondary prevention of diabetes. Dietary flavonoids are a structurally diverse set of naturally occurring polyphenolic compounds in plant-based foods, and flavan-3-ols are derivatives of flavanols, a major subclass of flavonoids, that include complex, bioactive molecules found in cocoa beans, tea leaves, grapes, red wine, and other foods. The rediscovered healing power of the cocoa bean. Cocoa is made from the bean of the cacao tree, Theobroma cacao, and has a long history of medicinal use and potential health benefits based upon its flavanol and procyanidin content. Cocoa extract also contains methylxanthines such as theobromine and caffeine, which may enhance the vascular and central nervous system effects of cocoa flavanols. Numerous short term, small-scale dietary intervention studies have examined the cardiovascular effects of flavanols and procyanidins, which have included well-characterized cocoa and cocoa product test materials linked to cardiovascular benefits. These trials have provided broader insights on the absorption, metabolism, and excretion of flavanols in humans with those focused on cocoa flavanol intake (as beverages, supplements, or chocolate) at up to 2000 mg/d and up to 1 y of treatment. Data have shown improvements in several biological mechanisms involved in cardiovascular disease, such as the ability of blood vessels to widen (“endothelium-dependent vasodilation”), blood pressure, inflammation, and platelet activation and provide insight into cocoa’s potential vascular effects due to intake of the flavanol (−)- epicatechin. Even though meta-analyses of such studies support benefits for flavanols on cardiometabolic biomarkers, prospective studies examining cocoa products restricted to chocolate intake or to usual levels of dietary flavanol intake with risk of cardiovascular disease (CVD) have been inconsistent, likely due to uncertainty of cocoa flavanol content and measurement error. “COSMOS is the first trial testing how these individual or combined cardiovascular mechanisms may translate into longer-term reductions in clinical cardiovascular events.” However, until recently, no large-scale trials have evaluated flavanol-rich cocoa extract containing all potential bioactive components of the cocoa bean on clinical cardiovascular outcomes. To address this question, Howard Sesso and a team of investigators from the Brigham and Women’s Hospital and Harvard Medical School, Boston, MA initiated the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS), a large-scale randomized double blind, placebo controlled trial supported by the company Mars Edge and the National Institutes of Health. The COSMOS study aimed to test a supplement prepared from cocoa bean extract and a typical multivitamin in the prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major cardiovascular disease and recently diagnosed cancer. Participants were randomly assigned to the cocoa bean extract supplement [500 mg flavanols/d, including 80 mg (-)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction, stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. After a median of 3.6 years of treatment, the investigators found that among older women and men with high compliance, flavanol supplementation significantly reduced cardiovascular death by 27%, whereas the risk for individual cardiovascular outcomes (such as myocardial infarction, stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina), or for the number of total cardiovascular events were not significantly reduced compared to the placebo arm. Finally, cocoa extract had no effect on the secondary outcomes of total invasive cancer and major site-specific cancers. Does a piece of chocolate a day keep the doctor away? As discussed in a recent podcast with Hagen Schroeter, Chief Science Officer of Mars Edge, the cosponsor of the COSMOS study, the answer is a definite no. Even though this large-scale study was originally designed to demonstrate the health benefit of eating chocolate, the main commercial product of the parent company Mars, any such claim had to be publicly withdrawn for several reasons. Any health benefits from consuming flavanols from commercial, tasty chocolate products would be negated by the simultaneous consumption of excessive calories in the form of sugar, fat and emulsifiers contained in these products. Moreover, while the raw material from which chocolate is made is the flavonoid rich cocoa bean, the extensive processing of the bean extract results in a depletion of the end product of any health promoting flavanols. Finally, the metabolism of the ingested flavonoid is highly dependent on the composition of the gut microbiome, breaking the nonabsorbable parent compound into the smaller metabolites, including the compound gamma valerolactone which can be detected in the blood. Not every individual has the right composition of such microbes to effectively generate the absorbable compound, a situation that was reflected in significant interindividual variation of clinical benefits. Based on these caveats and the impressive findings of the COSMOS study, is it beneficial to take a daily supplement of 1,000 mg of Cocoa flavanols? The evidence for such a recommendation is definitely a lot stronger than for most other supplements or multivitamins on the market, and may be worth the cost associated with the chronic intake of this supplement. If the primary mechanism underlying the flavanols’ benefit on the heart and on the brain (evidence not discussed in this post) is indeed the combination of beneficial effects on the blood vessels supplying these organs, it is a prudent investment in overall health when combined with other health promoting lifestyle changes such as exercise and healthy diet. And for the chocolate lovers out there: Continue to indulge in a piece of delicious chocolate after a healthy dinner, but don’t expect it will protect your heart! Going gluten-free is a popular trend fueled by the media, the internet, and a sizable group of medical practitioners. This trend is based on the claim that a gluten free diet (GFD) has vast benefits for a number of disorders affecting mind and body. A National Health and Nutrition Examination survey estimated that by 2014, 2.7 million US adults without celiac disease adhered to a GFD, increasing by more than 3-fold since 2009. This may be owing to gastrointestinal symptoms erroneously attributed to gluten intake, as in nonceliac gluten sensitivity. Alternatively, the GFD, popularized by the media and consumer-directed marketing, may be used by patients because of various perceived health benefits. The economic impact of this trend is remarkable. The gluten-free products market size was valued at $4.3 billion in 2019 and is estimated to reach $7.5 billion by 2027. Gluten-free labels can now be found on almost every food product, even on water bottles and pill box labels. A series of large, well designed epidemiological studies from the Harvard T.H. Chan School of Public Health under the leadership of Andrew Chan has provided strong evidence refuting a role of gluten in common brain and gut disorders, or a benefit of a GFD for any serious health problem. In a study looking at the long-term intake of gluten and cognitive function among a cohort of 13,494 women at midlife without a celiac disease diagnosis, there was no statistical evidence of any association of long- or short-term consumption of wheat, barley or rye – the major sources of gluten – and “brain fog”, a condition reflecting compromised cognitive ability. According to the study authors, the only individuals who benefitted from avoiding gluten were the small number of patients with celiac disease. In similar studies, no evidence between gluten intake and cancers of the gastrointestinal tract or cardiovascular risk were identified. However, the authors emphasized that avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. They recommended that the promotion of gluten-free diets among people without celiac disease should not be encouraged. In the most recent study, the Harvard investigators aimed to examine the relationship between dietary gluten and the risk of inflammatory bowel diseases (IBD) in adults without celiac disease. Inflammatory bowel diseases, including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the gastrointestinal tract that are thought to result from a dysregulated immune response to environmental and microbial stimuli in a genetically susceptible host. Although several hundred gene polymorphisms have been identified, the total variance of IBD risk explained by known genetic factors is less than 14%, highlighting the significance of environmental factors in disease development. One important environmental factor is diet, likely owing to its influence on gut microbiota composition, mucosal barrier function, and mucosal inflammation. IBD is associated with an increased risk for celiac disease, although nonceliac gluten sensitivity also is commonly reported by patients with IBD, and some patients report improvements in gastrointestinal symptoms following dietary gluten restriction. There are several possible reasons to explain such a benefit. It may be due to the fact that these patients were suffering from undiagnosed celiac disease or by an effect of gluten on IBD disease activity. To answer these questions, the Harvard investigators explored the relationship between dietary gluten intake and the risk of IBD in 3 large prospective US cohorts of men and women. These cohorts were made up by 208,280 US participants from the Nurses’ Health Study (1986–2016), Nurses’ Health Study II (1991–2017), and by the Health Professionals Follow-up Study (1986–2016). None of the participants had a diagnosis of IBD or celiac disease at baseline, and all of whom had completed semiquantitative food frequency questionnaires. The study identified 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up evaluation. (“Person-years” is a statistic for expressing incidence rates which is determined by the summing of the results of events divided by time). The results showed that dietary gluten intake was not associated with an increased risk of IBD. Adjusting their results for primary sources of gluten intake did not significantly change their estimates. When viewed together, the large, well-designed studies from the Harvard School of Public Health do not support commonly held beliefs about the detrimental effects of gluten consumption on cognitive function and gut health. Despite the impressive numbers of participants in the mentioned studies, there are limitations such as their epidemiological nature and the reliance on food frequency questionnaires to assess gluten intake. However, they point out the dangers of avoiding gluten in the diet and emphasize the considerable economic cost and lifestyle limitations that are associated with a restricted diet, that is often not based on scientific evidence but rather on food related fears. One of the puzzling aspects of our current epidemic of chronic non-communicable diseases is the continued increase in allergic and autoimmune disorders. While many factors may play a role in this phenomenon, recent research strongly implicates changes in interactions between the gut microbiota and the gut-associated immune system. “… host-microbe interactions during the first three years of life starting in utero (the “first thousand days”) are particularly important for the development of the immune system.” It has been known for some time, that host-microbe interactions during the first three years of life starting in utero (the “first thousand days”) are particularly important for the development of the immune system. Perturbations of the developing gut microbiota during this critical time (including C-section delivery, formula feedings, antibiotic exposure) can have long-lasting and often irreversible detrimental effects on health, including increasing the risk for allergic and autoimmune disorders. Until very recently, this microbe-mediated immune programming was thought to be initiated at birth when a newborn baby leaves the relatively sterile environment of the uterus and is exposed in the birth canal to the mother’s vaginal/rectal microbiota which begin to colonize the newborn’s gut. “… it seems increasingly possible that our mothers’ microbiomes may, to some extent, shape our health and well-being long before we are born. One such mechanism is the transfer of maternal antibodies to the fetus.” As discussed in an excellent review article by Drs. Carolyn Thomson and Kathy McCoy from the University of Calgary in The Scientist the maternal microbiome can exert its influence much earlier—on the developing fetus. Based on the accumulating science, it seems increasingly possible that our mothers’ microbiomes may, to some extent, shape our health and well-being long before we are born. One such mechanism is the transfer of maternal antibodies to the fetus. Antibodies generated by the pregnant mom’s immune system against her own microbiota as well as pathogenic microbes can cross the placenta to protect the fetus from infection. This remote control of the fetal microbiome via both bacteria-produced molecules and maternally derived antibodies appear to drive immune development in utero. “… mouse studies have shown that perturbing the microbiota of pregnant mice, either with antibiotics or dietary intervention, can lead to a variety of physiological alterations in the offspring with implications not only for diabetes, but for susceptibility to asthma, obesity, and colitis, as well as the progression of autism-like behaviors.” Less than a decade ago, as researchers began to question the role of the maternal microbiota during pregnancy several research groups performed epidemiological and preclinical studies to examine whether exposure of the fetus to antibiotics taken by the pregnant mother poses a risk to a child’s health. As fetuses don’t have their own microbiota, any microbe-mediated immune system modulation that may happen in the womb must be related to the gut microbes of the pregnant mother, and antibiotic exposure of the mother during pregnancy would disrupt this. As shown in mouse studies, prenatal antibiotic exposure influenced the development of type 1 diabetes, an autoimmune disease in the offspring. Subsequent mouse studies have shown that perturbing the microbiota of pregnant mice, either with antibiotics or dietary intervention, can lead to a variety of physiological alterations with implications not only for diabetes, but for susceptibility to asthma, obesity, and colitis, as well as the progression of autism-like behaviors. In most circumstances, manipulating the maternal microbiota by chronic stress, antibiotics or diet are vertically passed from mother to offspring at birth, and subsequently alters both the infant’s microbiome and immune development. It has therefore proven challenging to attribute the immune system changes described in most of these studies to the maternal microbiota directly, as opposed to those mediated by the newly seeded microbiota of the neonate. However, recent research is beginning to demonstrate that the maternal microbiota can shape both the immune and nervous system development of the offspring remotely, via different communication channels. “… the intestinal immune system must quickly learn to differentiate between innocuous and beneficial food components and benign microbes, and harmful molecules and pathogens which require the triggering of a successful defense against them.” By adulthood, the intestine is home to the body’s largest collection of immune cells, about 70% of the entire immune system. Being located in such close connection to the intestinal contents transporting an enormous number of foreign antigens derived from both the microbiota our diet and ingested chemicals, the intestinal immune system must quickly learn to differentiate between innocuous and beneficial food components and harmful molecules, between benign microbes and pathogens which require the triggering of a successful defense against them. Moreover, even beneficial microbes can quickly become harmful if they come into contact with specific receptors (so called toll like receptors or TLRs) on gut-associated immune cells like dendritic cells, which extend into the intestinal mucus layer, or translocate into the bloodstream through a “leaky gut”. Such translocation of gut microbes from the gut into the bloodstream has been reported under conditions of chronic stress and when consuming a Western diet. The immune system of a newborn infant is inexperienced. Despite some early reports to the contrary, the fetus is not thought to be colonized with its own microbial communities before birth. Traditionally, researchers thought that maternal antibodies transferred across the placenta were specific to infectious microbes that might infect the baby while its own immune system was still developing. We now know that maternally derived antibodies can also bind commensal bacteria—and that this helps to keep these nonpathogenic bacteria from crossing the epithelial barrier as a newborn’s gut is rapidly colonized by a vast array of unfamiliar microbes. “Different components of breast milk also play an important role in mediating the maternal influence on the developing infant microbiome…” According to the American Academy of Pediatrics, babies should be breastfed until they are 1 or older, and the Centers for Disease Control and Prevention states that breast milk is the best source of nutrition in those early months. In addition to providing optimal nutrition for the baby, different components of breast milk play an important role in mediating the maternal influence on the developing infant microbiome, including the Human Milk Oligosaccharides (HMOs) and maternal antibodies which can interact directly with the microbial inhabitants of the infant’s gastrointestinal tract. The medical and economic realities of new parenthood in America can make that one-year finish line an impossible goal for many mothers. By six months, the majority of new mothers give their babies some formula, for reasons ranging from problems with latching and milk supply to the demands of work outside the home. Aggravating this problem, there is now a nationwide formula shortage, driven by supply chain problems and exacerbated by the closure of a major production plant in February and the recall of select infant formulas. Both HMOs and antibodies are unique to human breast milk, and not provided by baby formula. While the HMOs, which are influenced both by maternal genes and diet, are large, non-absorbable molecules essential for the initial organization and development of the microbial ecosystem, the antibodies contained in breast milk keep populations of beneficial microbes in check and ensure that they stay in the gut lumen, preventing the inappropriate activation of the gut-associated immune system. The role of the maternal diet Another important component of the maternal influence on the infant’s microbiome and immune system are short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber by the mother’s intestinal microbes. The amounts and types of SCFAs that are produced in the mother’s gut and transferred to her baby depend on the maternal microbiome, which is in turn shaped by her diet. As discussed in detail in The Gut Immune Connection, when pregnant women eat a largely plant-based diet rich in fiber (Microbe Accessible Carbohydrates, or MACs), SCFA-producing microbes thrive, and increased amounts of SCFAs not only have an anti-inflammatory effect on the mother’s gut and body but are transferred to the developing fetus as well. Recent research suggests that SCFAs not only exert their anti-inflammatory effects but influence the maturation of the fetal immune system. Specifically, they stimulate the development of a population of immune cells (regulatory T cells, or Tregs), which produce anti-inflammatory molecules (in particular the cytokine IL-10) crucial for the prevention of immune activation in the gut. “Considering the extent of inflammatory diseases that can be controlled and suppressed by these anti-inflammatory immune cells simply through maternal dietary changes, these findings are likely to have far-reaching effects on a better understanding of developmental diseases…” These IL-10 producing cells are crucial for protecting our bodies from attacking our own tissues in the form of autoimmune diseases, as well as from allergies and asthma. They also teach our immune systems to tolerate food and friendly bacteria. These abilities make these cells a key factor in differential immune response to what is good or bad for our bodies. These immune cells are long-lived, and their “offspring” is assumed to be present throughout the life of the host. It is easy to see, how the influence of maternal microbiome, shaped by the mother’s diet can influence the development or maturation of these cells, could have far-reaching implications for the health of the offspring. This crucial effect of maternal diet on the anti-inflammatory ability of the offspring’s microbiome was demonstrated in a study from the Juntendo University in Tokyo which showed that pregnant dams that ate more fiber not only had increased amounts of several SCFAs in their feces, as well as increased butyrate in their blood, but that their pups had increased SCFAs in their blood at day 11 of life as well. Considering the extent of inflammatory diseases that can be controlled and suppressed by these anti-inflammatory immune cells simply through maternal dietary changes, these findings are likely to have far-reaching effects on a better understanding of developmental diseases like autism spectrum disorders. For example, a recent mouse study reported that a high fat diet in pregnant mothers induced a shift in the gut microbiome that negatively impacted social behavior in the offspring. As pointed out by the authors of this The Scientist article, implications of these new insights into the role of maternal diet, and its influence on the microbiome and immune system are extensive. For one, they could provide evidence for guidance about maintaining a healthy microbiota throughout gestation—for example, by eating a microbiome targeted diet (largely plant-based diet without ultra-processed foods and high amounts of sugar), avoiding unnecessary antibiotic use, and practicing simple stress reduction techniques. In addition, as the current baby formula crisis has brought to public attention, greater public health efforts should be made to enable mothers to nurse their babies during the first year, and not become fully or partially dependent on alternatives that lack some crucial components necessary for the development of a healthy gut microbiome. There are numerous benefits we have derived from our microbial co-inhabitants on planet Earth over millions of years. It starts with the realization that we humans wouldn’t be here if microbes living in the planet’s oceans had not developed the sophisticated language that ultimately was adopted by our nervous system and made our brains the most powerful computational devices in the universe. Equally important was the fact that microbes developed and continue to synergize with our metabolic machinery that keeps all of our cells alive. This body of wisdom has been stored in hundreds of millions of genes and handed down during evolution over several billion years. Even though only partially understood, this microbe-based wisdom still helps us to adapt to the many challenges we are faced in a rapidly evolving world. “The majority of our adult gut microbiome develops early on in life through vertical transmission from our mothers.” Fast forwarding to the arrival of humans some 1 million years ago, and particularly to the present, the best-known benefits of living in harmony with our gut microbes come from the interactions of these trillions of microbes, and the rest of our body, including the brain. Research has shown that lifelong diversity and richness of this largely stable gut microbiome is associated with a lower prevalence of many if not most chronic non-transmissible diseases. The majority of our adult gut microbiome develops early on in life through vertical transmission from our mothers. However, there are several environmental influences on our gut microbial ecosystem, including our diet, and microbes transmitted from household members, pets, and exposure to greenspaces. Another influence comes from a group of microbes that we add to our stable gut microbiota when we regularly consume a variety of naturally fermented foods. As shown in a recent study published by the Sonnenburg Lab at Stanford University, the consumption of a diet rich in a number of naturally fermented foods, is able to increase the diversity of the gut microbiome, even more than eating a fiber rich diet. And interestingly, this food-related transfer of microbes into our gut is not limited to fermented foods. Professor Gabriele Berg from Graz University of Technology in Austria has studied this question in great detail and has published some little-known aspects about the health benefits of consuming organically grown apples. In 2019, her group published a research article in the journal Frontiers in Microbiology, in which they compared the bacteria in conventional store-bought apples with those in visually matched organic ones. Stem, peel, flesh, seeds, and calyx – the straggly bit at the bottom where the flower used to be – were analyzed separately. “…the data showed that freshly harvested, organically managed apples harbored a significantly more diverse, and distinct bacterial community, compared to conventional ones.” Overall, the organic and conventional apples were occupied by similar numbers of bacteria. According to Berg, “Putting together the averages for each apple component, it has been estimated that a typical 240g apple contains roughly 100 million bacteria.” Organically managed apples harbored a significantly more diverse, and distinct bacterial community, compared to conventional ones. There are some major caveats to this study, including the fact that the conventionally grown apples were packaged and refrigerated for days before analysis. In contrast, the organic apples were analyzed immediately following harvest, and were grown on a different farm in Austria. Despite these methodological limitations, the study confirms previous results, showing that the majority of the bacteria found in apples were located in the seeds, with the flesh and skin accounting for most of the remainder. So, if you discard the core, as most apple consumers do – your intake falls to closer to 10 million! “Considering that 83 million tons of apples were grown in 2018, this source of ingested microbes is quite substantial.” Matthew Prior, science writer for the Frontiers journals stated wisely: “To the heroes among you who eat the whole apple: besides extra fiber, flavonoids and flavor, you’re also quaffing 10 times as many bacteria per fruit as your core-discarding counterparts.” Considering that 83 million tons of apples were grown in 2018, this source of ingested microbes is quite substantial. There is general evidence that the more diverse microbial ecosystem protects the apple against harmful bacteria and fungi, just like a diverse gut microbiome protects us against enteric infections. But does eating these apple-associated microbes provide any health benefits for us? Do the treatments that some apples go through before coming to your market, like spraying with insecticides, irradiating them to destroy harmful bacteria and covering them with a thin layer of wax to make them look more attractive have a negative effect on the apple’s microbial ecosystem? Certainly, the absence of these treatments could be one reason for the observed differences of the organically grown apples. While the final answers to these questions have not been shown in well controlled studies, based on Berg’s exciting research and studies looking into other health benefits of apples, one can make some well-informed speculations: Birgit Wasserman, Berg protégé and co-author of the study, suggested that “The microbiome and antioxidant profiles of fresh produce may one day become standard nutritional information, displayed alongside macronutrients, vitamins, and minerals to guide consumers … another key step will be to confirm to what extent diversity in the food microbiome [and flavanol content] translates to gut microbial diversity and improved health outcomes.”
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.The Stress That Evolution Has Not Prepared Us For
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.What Is All the Fuss About Boosting Our Immunity?
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.The Crucial Role of Diet in Colorectal Cancer Risk
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Why Are More and More People Living to 100?
However, current population trends around the world seem to be moving into a different direction as evolution had in mind. For poorly understood reasons, falling birthrates and increasing longevity have been going hand in hand in several countries around the world, turning large portions of these countries into what have been called Blue Zones. According to the Blue Zone concept, there are geographic regions around the world with an unusually high proportion of individuals living into their hundreds, so called centenarians. However, a closer look at epidemiological trends tells us that this phenomenon is not restricted to Blue Zones any more. Based on a 2022 estimate by the United Nations, there are currently 593,000 centenarians around the world and this population is growing fast. The UN projects there will be 3.7 million centenarians alive by 2050.
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.A New Holistic Understanding of IBS
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.The Amazing Evolution of the Goodman-Luskin Microbiome Center at UCLA
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.SIBO – Debunking Popular Myths in Irritable Bowel Syndrome
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Choosing The Right Seafood For Optimal Health
A 3-ounce serving contains over 300 mg of omega-3s and about a third of the recommended daily values of iron). Oysters are not only good for you, but for the environment. Oysters feed off the natural nutrients and algae in the water (which provides them with large amounts of omega-3), and which improves water quality.
The tiny, inexpensive canned sardine which has been popular in Europe for a long time, contains more omega-3s (1,950 mg!) per 3-ounce serving than salmon, tuna, or just about any other food; it’s also one of the few foods that’s naturally high in vitamin D. Many fish in the herring family are commonly called sardines. Sardines are a highly sustainable food source as they have a fast reproduction rate. Pacific sardines have rebounded from both overfishing and a natural collapse in the 1940s.
The numbers of wild salmon returning to spawn in Alaska’s rivers is being closely monitored, and if the numbers begin to dwindle, the fishery is closed before it reaches its limits. This close monitoring, along with strict quotas and careful management of water quality, means Alaska’s wild-caught salmon are both healthier (they pack 1,210 mg of omega-3s per 3-ounce serving and carry few contaminants) and more sustainable than just about any other salmon fishery.
Freshwater coho salmon is the first–and only–farmed salmon to get a Super Green rating. All other farmed salmon still falls on Monterey Bay Aquarium’s Seafood Watch “Avoid” list for a few reasons. Many farms use crowded pens where salmon are easily infected with parasites, may be treated with antibiotics, and can spread disease to wild fish (one reason Alaska has banned salmon farms). Also, it can take as much as three pounds of wild fish to raise one pound of salmon. Coho, however, are raised in closed freshwater pens and require less feed, so the environmental impacts are reduced. They’re also a healthy source of omega-3s–one 3-ounce serving delivers 1,025 mg.
Nearly all the trout you will find in the market is farmed rainbow trout. In the US, rainbow trout are farmed primarily in freshwater ponds and “raceways” where they are more protected from contaminants and fed a fish meal diet that has been fine-tuned to conserve resources.
Many tuna are high in mercury but albacore tuna–the kind of white tuna that’s commonly canned–gets a Super Green rating as long as it is “troll- or pole-caught” in the US or British Columbia. The reason: Smaller (usually less than 20 pounds), younger fish are typically caught this way (as opposed to the larger fish caught on longlines). These fish have much lower mercury and contaminant ratings and those caught in colder northern waters often have higher omega-3 counts. The challenge: You need to do your homework to know how your fish was caught or look for the Marine Stewardship Council (MSC) blue eco label.
In December 2009, the World Wildlife Fund put the bluefin tuna on its “10 for 2010” list of threatened species, alongside the giant panda, tigers, and leatherback turtles. Though environmental groups are advocating for protected status, the bluefin continues to command as much as $177,000 a fish. Bluefin have high levels of mercury and their PCBs are so high that EDF recommends not eating this fish at all.
Slow-growing and prized for its buttery meat, Chilean sea bass has been fished to near depletion in its native cold Antarctic waters. The methods used to catch them–trawlers and longlines–have also damaged the ocean floor and hooked albatross and other seabirds. The EDF has issued a consumption advisory for Chilean sea bass due to high mercury levels.
High mercury levels in these giant fish have caused EDF to issue a consumption advisory. Groupers can live to be 40 but only reproduce over a short amount of time, making them vulnerable to overfishing.
This strange fish resembles a catfish in that it has whiskers and is a bottom-dweller, but its light, fresh taste made it a staple for gourmets. The fish is recovering some after being depleted, but the trawlers that drag for it also threaten the habitat where it lives.
Like grouper, this fish lives a long life but is slow to reproduce, making it vulnerable to overfishing. As Seafood Watch puts it: “Orange roughy lives 100 years or more–so the fillet in your freezer might be from a fish older than your grandmother!” This also means it has high levels of mercury, causing EDF to issue a health advisory.
Most farmed salmon (and all salmon labeled “Atlantic salmon” is farmed) are raised in tightly packed, open-net pens often rife with parasites and diseases that threaten the wild salmon trying to swim by to their ancestral spawning waters. Farmed salmon are fed fish meal, given antibiotics to combat diseases and have levels of PCBs high enough to rate a health advisory from EDF. Recently, however, freshwater-farmed coho salmon have earned a Best Choice status from Seafood Watch. Consumer pressure may encourage more farms to adopt better practices.
According to a research study just published in the journal Environmental Research, eating just one serving of freshwater fish, caught in lakes and streams each year could have the same effect as drinking water heavily polluted with “forever chemicals” for an entire month, a new study finds. According to the study, the equivalent monthlong amount of water would be contaminated at levels 2,400 times greater than what’s recommended by the Environmental Protection Agency’s (EPA) drinking water health advisories. The research added that locally caught freshwater fish are far more polluted than commercial catches with per- and polyfluorinated substances (PFAS) — so-called forever chemicals that are notorious for their persistence in the body and the environment.
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.
E. Dylan Mayer is a graduate from the University of Colorado at Boulder with both a major in Neuroscience and minor in Business. He is fascinated by the interactions of brain, gut and microbiome, and the role of nutrition in influencing the health of our microbiome, as well as our own well-being. He is currently earning his Master’s Degree in Human Nutrition at Columbia University.Depression and The Gut Microbiome – The Unresolved Chicken and Egg Question?
microbiome.
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.One More Word About Extra Virgin Olive Oil
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Non-Nutritive Sweeteners – Good or Bad for our Metabolic Health?
Elvira Rostanzo, MSc is a registered Biologist who graduated in Human Nutrition. She is a practicing nutritionist and is currently attending the Specialization School of Food Sciences at University of Siena in Italy.The Crucial Role of Diet and the Gut Microbiome in Colorectal Cancer Risk
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.
Jill Horn is a recent UCLA graduate with a degree in Neuroscience. She is deeply interested in the interconnectedness of body, mind, and spirit takes an integrative approach to health and well-being.The Exciting New Science Underlying IBS Treatments
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Yvon Chouinard, the Ultimate Climate Philanthropist
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Is A Healthy Diet Good For The Planet?
known to contribute to poor health outcomes (e.g., sugar, salt, added fats, refined grain flours).
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Chronic Stress
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Does a Diet High in a Variety of Fermented Foods Protect You Against Cognitive Decline and Colon Cancer?
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.The Myth of Multivitamins and Other Supplements
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Have We Made Progress in Fecal Microbial Transplantation?
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Olive Oil – Medicine Produced by Nature and Refined by Human Expertise and Traditions
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Are Bioactives the New Magic Treatment for Cardiovascular Disease?
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.Do Millions of People Need a Gluten Free Diet?
Empiric gluten avoidance likely is not without negative health consequences. Avoidance of gluten from whole grains may affect the risk for type 2 diabetes mellitus, cardiovascular disease, and mortality. In addition, indiscriminate exclusion diets have even been linked to malnutrition and disordered eating behaviors.
While a GFD is essential for people with gluten allergies and celiac disease – a serious autoimmune disorder of the small intestine – the existence of non-celiac gluten sensitivity and its involvement in many gut and brain disorders has been challenged by a number of epidemiological studies and controlled clinical trials.
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.How Mom’s Gut Microbes Can Influence the Health of the Offspring
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA and the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA.An Apple a Day Keeps the Doctor Away
