What I Tell My Patients About Probiotics
As a longtime investigator in brain gut microbiome interactions, practicing gastroenterologist and frequent host on gut health related podcasts, I am confronted with questions about probiotics on an almost daily basis.
Patients who are concerned about their gut health, want to know which probiotic is best for them, and how they can identify the right product from hundreds of such products on the internet, all claiming scientifically proven effectiveness. Are billions of colony forming units (CPUs) and a large number of different strains necessary to have beneficial effects?
Colleagues want to know if there is any credible evidence for health benefits of any probiotic on gut disorders like IBS, IBD, “SIBO” or antibiotic-induced diarrhea. Can probiotics reduce anxiety? Improve symptoms in autism spectrum disorder?
Research collaborators want to know which probiotic to best select for research studies in IBS patients, or for studies on brain function in patients with anxiety or depression.
“…my scientific interest in probiotics didn’t start until about 10 years ago, when my research group embarked on the first human study to evaluate the effect of the regular consumption of a fermented milk product…”
Even though the consumption of beneficial microbes with fermented foods, in particular different fermented dairy products, sauerkraut and brewer’s yeast (picked up at the local brewery) for stomach troubles was a traditional folk remedy when I grew up in Bavaria (it actually worked most of the time!), my scientific interest in probiotics didn’t start until about 10 years ago, when my research group embarked on the first human study to evaluate the effect of the regular consumption of a fermented milk product with a group of different microbes on the brain.
While a number of earlier studies in laboratory mice had clearly demonstrated an effect of the gut microbiome (and the lack of a normal microbiome) on behavior and brain function, our study was the first to demonstrate that ingested microbes could actually signal to the brain and change networks concerned with emotion regulation.
As the study subjects were all healthy young women, we weren’t able to demonstrate an associated psychobiotic effect, e.g., a microbially induced change in anxiety or abdominal pain. No human study has clearly demonstrated such a psychobiotic effect in patients with psychological problems to date in an unequivocal way.
Probiotics have been defined by an international expert panel as “Live microorganisms that when administered in adequate amounts confer a health benefit on the host”. Driven by the high popularity of concepts like gut health, leaky gut and immunity, there has been an intense and rapidly growing scientific and commercial interest in probiotics. More than 12,000 papers on the topic have been published in the last 7 years, and probiotic sales have been estimated to amount to $40 billion and to reach $64 billion by 2023.
“…despite these impressive numbers, many questions remain…”
However, despite these impressive numbers, many questions remain about best strains, number and combination of strains, personalization of treatments based on individual gut microbial composition and function, and clinical effectiveness in specific target populations.
While superb study results obtained in experimental mouse models continue to be published in high profile scientific journals, human studies have largely failed to reproduce the same dramatic outcomes. There are many reasons for this discrepancy, the major ones being the high interindividual variation between human subjects (compared to the genetic homogeneity of inbred mice), the challenge of controlling dietary intake in humans, lack of attention being paid to sex-related differences, sample size of study populations, and in terms of psychobiotics, poorly selected candidate probiotic strains that are either chosen for their cost to manufacture at scale, legacy research, or single mechanism of action, or the vast differences between the mouse and human brains.
Along the same lines, there is only a handful of probiotics that have gone through the rigorous approval process by federal agencies like FDA. Until these questions have been answered, consumers, not being aware of the above problems, are more influenced by the prominence and reach of social media influencers and clever marketing campaigns than by objective evidence.
Considering this state of the field, how do I answer the questions I am being asked by my audiences?
My initial answer is always that microbiome science is a very young field, that our understanding of the complexities of our gut microbial partners remains very limited and that we underestimate the power of placebo, but that we know enough to realize the phenomenal implications of the field for many aspects of our health.
As an integrative gastroenterologist, I am guided by a large body of empirical evidence that the consumption of naturally fermented foods (which humans have consumed for thousands of years, but which don’t necessarily fulfill the criteria required for the marketing as a probiotic) is associated with health benefits and is good for gut microbial diversity and health as recently demonstrated in a high quality clinical trial evaluating the effects of a diet high in naturally fermented foods and a fiber rich diet.
As a scientist, I am guided by the rapidly evolving science and by evidence derived from a few high quality clinical studies (1, 2, 3), which have demonstrated a clinically meaningful effect of certain probiotic strains and of naturally fermented foods on objective outcomes in human subjects, such as shape and consistency of bowel movements, gut microbial diversity and on functional brain changes.
While there does seem to be a role for specific probiotics to improve health, many of the commercially available probiotic strains are generic, understudied, or selected for industrial purposes like ease of manufacture or a high potency yield. Very few commercial products have sequenced the strains or generated data demonstrating the formulation effectively survives the gastrointestinal system and delivers live probiotic cells inside the body.
“There are companies and researchers pushing the field forward with scientific rigor and novel approaches…”
In this regard, I wanted share that there are companies and researchers pushing the field forward with scientific rigor and novel approaches to formulation, testing and validation. Seed Health, a microbial sciences company I have known and recently became a Scientific Advisor to, has developed a complex, multi-strain probiotic and prebiotic formulation (DS-01TM) with data to support the formulation, strains, gastrointestinal transit, and biological effects.
Seed has assembled a strong scientific team and Scientific Board, including pioneers in the field of probiotics, to work on data generation (Hill et al 2014, Gibson et al 2017, Reid et al, 2019). Seed’s approach has been to validate candidate probiotic strains based on their clinically validated success in improvement in different health outcomes and/or molecular upregulation of markers of gut barrier integrity.
The probiotic consortium they assembled was combined with a novel prebiotic, a pomegranate polyphenol which demonstrably increases beneficial Bifidobacterium and Akkermansia, which directly stimulate a favorable gut microbial balance. The polyphenol and its microbial breakdown products are also associated with anti-inflammatory and anti-oxidizing benefits that afford protection against poor immunity, metabolic upsets, and aging.
In summary, there is no question that probiotic consumption in the US will continue to grow, driven to a large extent by online marketing campaigns, unsubstantiated claims, and poor stewardship of the scientific use of the term, ‘probiotic’. The powerful placebo effect will assure that many people will perceive and report health benefits from their daily probiotic cocktail. However, encouraged by a handful of innovative companies willing and able to invest in rigorous scientific evaluation (including but not limited to Seed, Danone, and Pendulum), I believe that the Golden Age of scientifically proven pre-, pro- and syn-biotics for improving gut and brain health, is still ahead of us.
NOTE: I’ve partnered with Seed because I strongly believe in their transparent and evidence-based approach to develop a symbiotic with benefits your gut health. This post contains affiliate links, and if you make a purchase through these links I may receive a referral credit for your order.
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.