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Fascinating study reporting results obtained from nearly 12,000 people around the world as part of the American Gut Project

Fascinating study reporting results obtained from nearly 12,000 people around the world as part of the American Gut Project

‘Largest’ microbiome study weighs in on our gut health

Fascinating study reporting results obtained from nearly 12,000 people around the world as part of the American Gut Project.  Major findings of this landmark study are the fact that it is the diversity of plant based foods that a person consumes (and not just the fact that somebody identifies as vegan or vegetarian) that influences gut microbial diversity and relative abundances, and that there is an association of mental disorders with gut microbial function, with gut microbial characteristics being more similar amongst several psychiatric diseases than compared to healthy individuals.  Even though the findings are solely based on associations, and do not allow to make statements about causality, they represent the most comprehensive analysis of gut microbial data published to date.

 

Important implications for development of future therapeutic strategies using engraftment of microbial species into our gut microbiome.

Important implications for development of future therapeutic strategies using engraftment of microbial species into our gut microbiome.

An exclusive metabolic niche enables strain engraftment in the gut microbiota
Elizabeth Stanley Shepherd, William C. DeLoache , Kali M. Pruss , Weston R. Whitaker & Justin L. Sonnenburg

 

After programming of the general compositional architecture of the gut microbiota in early life, the established microbial ecosystem remains fairly stable and resilient to perturbations throughout life. Such perturbations include infections, colonic cleansing, diet or antibiotic intake.  While this is stability and resilience is generally of great benefit for the host, it becomes a challenge when we try to modify an compromised microbiome by the intake of probiotics or fecal microbial transplantation.  Before we can move on to modulate a maladaptive or disease related gut microbial composition by such interventions, there is a need for basic insight into the factors that influence whether and under what circumstances new strains of bacteria can integrate into a pre-existing, complex microbiota.

This latest study from the Sonnenburg lab demonstrates in mice that the combined administration of a specific sugar molecule called porphyry and a microbial strain that is not part of the normal gut microbiota but which contains the genes for the exclusively utilization of this sugar molecule results in the engraftment of the new microbe into the existing gut microbial ecosystem. As stated by the authors: “Privileged nutrient access enables reliable engraftment of the exogenous strain at predictable abundances in mice harbouring diverse communities of gut microbes.

These findings have important implications for the development of future therapeutic strategies using the engraftment of lacking or novel microbial species into our gut microbiome.  Such strategies may become important of the treatment of such various disorders as autism spectrum disorders, inflammatory bowel disorders and obesity.

 

 

Indisputable Health Benefits of the Traditional Mediterranean Diet

Indisputable Health Benefits of the Traditional Mediterranean Diet

Backed by the strongest scientific evidence, the traditional Mediterranean diet remains the healthiest diet available, with health benefits for a variety of common chronic diseases, including the protection against coronary vascular disease, some forms of cancer, and stroke.

The traditional Mediterranean diet is characterized by a high intake of olive oil, fruit, nuts, various vegetables, and cereals; a moderate intake of fish and poultry; a low intake of dairy products, red meat, processed meats, and sweets; and a moderate amount of red wine consumed with meals. This kind of diet that has evolved over hundreds of years in countries surrounding the Mediterranean Sea is obviously fundamentally different from the modern diets promoted for their often unsupported health benefits today, including the paleo, ketogenic, or grain- and gluten-free diets.

One of the most well-known recent clinical trials in support of the Mediterranean diet was the PREDIMED study, which showed that in subjects with an increased risk of cardiovascular events, the adherence to a Mediterranean diet which was either supplemented with nuts or with extra virgin olive oil provided a significant reduction of cardiovascular events, compared to a control diet (advice to reduce dietary fat). The benefits of both types of Mediterranean diet were so striking that the clinical trial was stopped after a median of 4.5 years.

Even though additional cultural, social and lifestyle factors may be involved, the authors of the study speculated that the lower cardiovascular mortality observed in Mediterranean countries compared to northern European countries or the United States can be explained by adherence to a Mediterranean diet. While it has already been demonstrated in small scientific studies that this diet has positive effects on brain function and even structure, there are now several controlled studies evaluating the beneficial effects of Mediterranean diet in depression, Alzheimer’s disease, and Parkinson’s disease.

A Mediterranean diet is not only good for the heart and the brain, as a recent study on its effect on chronic liver disease demonstrates. The study performed in 1521 patients with Non-Alcoholic Fatty Liver Disease (NALFD) demonstrated that one of the most common liver disorders can effectively be treated simply by adhering to a Mediterranean style, e.g. largely plant based diet.

Amongst the many factors contributing to the undisputable benefits of the Mediterranean style diet are a reduction of unhealthy components of the typical North American diet, which is characterized by high consumption of animal products, refined sugars, processed foods and reduced intake of plant based food (e.g. dietary fiber). It is well known that these factors, in particular the reduction of dietary fiber intake, contribute to a change in the gut’s microbiome. This leads to a low grade activation of the gut’s immune system resulting in increased blood levels of immune system mediators (a condition referred to as metabolic toxemia), affecting every organ in the body, including the heart, the liver and the brain.

There are things to keep in mind when talking about the Mediterranean diet:

The Americanized version of this diet, such as the widely advertised thick layered pizza dough covered with with tons of cheese, large pasta dishes with creamy sauces and lots of red meat, is fattening and most likely no longer provides the benefits reviewed above (even though this has never been tested scientifically).

Traditional diets consumed in countries around the Mediterranean, including but not limited to Spain, Greece and Lebanon, are made up of similar ingredients and presumably have similar health benefits. However, the modern modifications of dietary habits in these countries with increased portion sizes, introduction of high caloric and processed fast foods, increased consumption of animal products, e.g. meat and animal fats, and the modernization of how the consumed plants are grown may have diluted some of the benefits of the traditional forms of the diet.

Mediterranean and Italian diets are not the same. As described in an interesting article by Frank Jacobs, there is a large variety of food and dietary habits based on the different geographic regions of Italy: in Sicily and Sardinia, food is obviously quite different from that in Milan, Bologna or Bolzano in the North. When I discussed this with Marco Cavalieri, producer of organically grown wine and extra virgin olive oil in Fermo, Italy, he told me that generally one can say that the Mediterranean diet is fully adopted in the central and southern Italy, and less so in Northern Italy. But despite the diversity of foods between the different geographic regions, legumes, cereals, vegetables, fruit, fish and extra virgin olive oil make up the basic ingredients.

For example, even in the northern regions, traditional dishes, such as the Milanese risotto, today are made using extra virgin olive oil and accompanied with seasonal vegetables. Marco believes that with its health benefits being widely appreciated, the concept of Mediterranean diet is widespread throughout the Italian cuisine. There is evidence that life expectancy in central-southern Italy, in particular Sardinia (one of the famous Blue Zones) is higher, suggesting that it is the greater adherence to the traditional diet that provides this benefit.

Besides similarities in diet, people in Mediterranean countries share a strong connectedness with the world, including the regions they live in, with family and friends, with history, traditions and religion. As I discussed in The Mind-Gut Connection, this “mind component” of the Mediterranean diet is likely to play an important, yet still underappreciated role in its observed health benefits.

IBS Patients Obtain Robust, Enduring Relief from Home-Based Treatment Program–And Physicians Agree

IBS Patients Obtain Robust, Enduring Relief from Home-Based Treatment Program–And Physicians Agree

“This study clearly established the clinical value of a #MindBased intervention for Irritable Bowel Syndrome (IBS)… showing that this should be offered to patients not as a last resort but as a safe and effective first or second-line therapy.” – Dr. Emeran Mayer

Landmark, NIH-funded multisite study finds IBS patients who learned to control severe GI symptoms at home saw as much benefit as those treated with multiple clinic visits…

BUFFALO, N.Y. — In the largest federally funded clinical non-drug trial for irritable bowel syndrome (IBS), patients with the most severe and persistent symptoms achieved robust and sustained relief by learning to control symptoms with minimal clinician contact. Led by University at Buffalo researchers in collaboration with colleagues at New York University and Northwestern University, the study is published in Gastroenterology.

The research is a product of 20 years of funding from the National Institute of Diabetes, Digestive and Kidney Diseases of the National Institutes of Health, and one of the largest, behavioral medicine trials not including a drug arm. It reflects a longtime partnership between researchers at UB and NYU, who pooled their respective expertise and talents to develop and test a novel treatment strategy.

Of 436 patients recruited at UB and Northwestern, 61 percent reported symptom improvement two weeks after home-based behavioral treatment ended compared to 55 percent in clinic-based treatment and 43 percent who received patient education. The treatment benefit also persisted for as long as six months after treatment ended.

“This is a novel, game-changing treatment approach for a public health problem that has real personal and economic costs, and for which there are few medical treatments for the full range of symptoms,” said Jeffrey Lackner, PsyD, lead author, professor in the Department of Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB and director of its Behavioral Medicine Clinic. He is affiliated with UB’s Clinical and Translational Science Institute.

Women are disproportionately affected

IBS is a persistent and difficult-to-treat condition that is one of the most common diseases that gastroenterologists and primary care physicians treat. It’s characterized by chronic abdominal pain, diarrhea and/or constipation. Medical and dietary treatment have a disappointing track record of relief for many patients.

Afflicting between 10 and 15 percent of adults worldwide, most of whom are female, the condition creates a public health burden that causes pain, isolation and frustration, all of which impair quality of life. Beyond the personal toll, Lackner said, the economic burden of IBS in the U.S. is estimated at $28 billion annually.

“These findings will be welcomed by many women and men, who have unfortunately been stigmatized, marginalized and too often treated as ‘head cases’ merely because no definitive cause for their symptoms is identified through routine medical testing.”
-Jeffrey Lackner, PsyD, Professor, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences

This treatment will help address a major barrier to quality health care faced by those living in rural areas, Lackner added, because now these patients will have access to a state-of-the-art treatment once only available in metropolitan areas.

According to NYU Silver School of Social Work Professor James Jaccard, PhD, a key investigator on this research program since its inception in 2000, “The creative development of this symptom-management approach for IBS can affect millions of people, primarily women, who suffer from this often stigmatized and poorly understood condition. By integrating perspectives from medicine and the social sciences, it illustrates the power of team-oriented and multidisciplinary approaches to reducing health care disparities in vulnerable populations.”

While IBS affects mostly women, Lackner said this study is noteworthy because 20 percent of the patients were male, many of whom are themselves reluctant to seek help. “These men are more likely to reach out for help if they can access treatment that is brief and home-based,” he said.

Brain-gut connections

The treatment consists of a form of cognitive behavioral therapy (CBT) that teaches practical skills for controlling gastrointestinal symptoms, either during 10 clinic visits, or four clinic sessions in conjunction with self-study materials developed by Lackner in a previous NIH grant. Both CBT treatments focused on information on brain-gut interactions, self-monitoring of symptoms, triggers and consequences, worry control, muscle relaxation and flexible problem-solving.

“The treatment is based on cutting-edge research that shows that brain-gut connection is a two-way street,” Lackner explained. “Our research shows that patients can learn ways to recalibrate these brain-gut interactions in a way that brings them significant symptom improvement that has eluded them through medical treatments.”

Physicians and patients agree on improvement

Lackner added that the study’s strength is underscored by the fact that both patients and the gastroenterologists, who evaluated patients and were unaware of which treatment patients were assigned, reported similar rates of symptom improvement as patients.

“One measure of the strength of clinical-trial findings is when two data sources report similar data about an endpoint,” he explained. “In our study, there was striking similarity between the treatment response reported by patients and ‘blind’ assessors. This pattern of agreement from patients and physicians shows that we see very real, substantial and enduring improvement in GI symptoms immediately after treatment ends and many months later.”

‘Mind-based intervention’

The research holds special interest for Emeran Mayer, MD, PhD, professor in the David Geffen School of Medicine at UCLA and executive director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, an internationally known expert on the interactions between the digestive and nervous systems and women’s health.

“This study clearly established the clinical value of a mind-based intervention for IBS,” said Mayer. “The success of this research shows that this should be offered to patients not as a last resort but as a safe and effective first or second-line therapy. It’s very different from the pharmaceutical model where you are searching for magic-bullet medications. With current medications, you cannot treat the whole patient. The medications can improve their bowel habits, but it’s not a complete treatment for the patient with IBS.”

Lackner oversaw the training of clinicians who work with Mayer at UCLA on the UB program. The two have been building on this work with a groundbreaking study of how the microbiome of IBS patients influences their response to cognitive behavioral therapy. The collaborative work is jointly funded by a $2.3 million NIH grant to UCLA, the lead institution, and UB. Results from that study are forthcoming.

Paper published in Gastroenterology

Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome

For additional information about this study, contact: Ellen Goldbaum, University at Buffalo

 

 

The Germs That Love Diet Soda

The Germs That Love Diet Soda

The Germs That Love Diet Soda is an excellent article in the New York Times by science writer Moises Velasquez-Manoff about the potential dangers associated with consuming processed foods.  While it cannot be emphasized enough that eating organic, fresh, fiber rich, low fat and low sugary foods is good for our health, caution is necessary when extrapolating from recent microbiome research performed largely in mice to human health. Some reflections:

  1. Findings obtained in experimental rodent models generally living in artificial living conditions and eating unnatural food are often not translatable to humans.  So unless confirmed in well controlled human studies, avoid premature conclusions from such studies for your own health.
  2. Not all “processed” food are the same.  Cooking, fermenting, baking food all involve the processing of raw materials to increase flavor or digestibility.  There is nothing wrong with eating your fermented milk products, cheese, pickled olives  or a good glass of wine.  On the other hand the term processed food with negative implications should be reserved for adding artificial sweeteners, high amounts of fructose, high amounts of vital gluten, chemical preservatives, food colors and other substances to food. While our gut microbes with their millions of genes are pretty good at breaking down such chemicals which they have never been exposed to in evolution, so called xenobiotics, evolution hasn’t foreseen the potentially harmful effects of these breakdown products, and the food safety testing by the FDA is based on acute toxicology essays, and not on the long-term effects such chemicals may have on our bodies.
  3. The problem with the modern western diet that it not only contains many of these bad purposefully added substances, but a whole range of other “hidden” chemicals associated with modern food production and environmental toxins.  This is particular the case with the constant stream of low dose antibiotics from meat and plant products (in addition to the overprescribed, and unnecessary antibiotics for presumed bacterial infections), and residues of pesticides (microbes are masters in metabolizing the active ingredient of glyphosate, the weed killer better known as round up into a potentially toxic chemical for our bodies.

Despite these caveats, the evolving microbiome science is confirming what people and cultures around the world have either intuitively practiced or consciously pursued for centuries:  the benefits of a largely plant based diet, limited intake of sugary and high fat foods, grown without the addition of chemicals, and consumed in modest amounts.

For a more in-depth exploration of topics related to the microbiome, read The Mind Gut Connection.