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International Dairy Summit 2018 in Daejeon in South Korea

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

By Prof. Seppo Salminen PhD, University of Turku, Finland

The International Dairy Federation (IDF) convenes annual meetings that bring together scientists and industry professionals to discuss issues foremost to the production of safe and nutritious dairy products globally. Since probiotics find a home in so many dairy foods worldwide, ISAPP and IDF have some overlapping interests.

ISAPP president, Prof. Seppo Salminen of University of Turku, spoke at IDF’s International Dairy Summit 2018 on the potential for fermented foods to fight diseases and improve nutrition. He emphasized that many fermented foods contain a diverse collection of live microorganisms, which likely support our gut microbiota, perhaps even promoting gut microbiota resilience. Further, he stated, “Fermented dairy products, especially yoghurt, which combines milk, microbial starter cultures and pre-digested nutrients for human use, can be considered for future food-based dietary guidelines or recommendations focusing on beneficial microbe intake for gastrointestinal and other health effects.”

Another speaker, Prof Bruno Pot, discussed the global situation with regard to health claims for fermented dairy products. He focused on the situation in the European Union, where the only allowed health claim for probiotics is the benefit from live bacteria (Lactobacillus bulgaricus and Streptococcus thermophilus) in yoghurt reducing symptoms of lactose maldigestion. He reported that yoghurt is becoming a mainstream food in Asia. Key growth drivers in Asia are the perceptions that yoghurt is a healthy product with its beneficial impact on the digestive and immune systems, and they offer a good source of protein and calcium. The symposium also explored ways to enrich food through product development and innovation, particularly to provide nourishment for vulnerable populations. The potential for new ingredients such as milk protein hydrolysate-calcium complexes as calcium sources in yoghurt production was recognized.

David Everett, Chair of IDF’s Standing Committee on Dairy Science and Technology, reported: “Holding the 6th edition of the Symposium on Fermented Milks in Asia is of tremendous value as the scientific research on fermented dairy and the interest in these products is growing in the region.”

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Probiotics and D-lactic acid acidosis in children

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

Prof. Hania Szajewska PhD, The Medical University of Warsaw, Department of Paediatrics, Poland and Prof. Seppo Salminen PhD, Faculty of Medicine, Functional Foods Forum, University of Turku, Finland

See related post ‘Brain Fogginess’ and D-Lactic Acidosis: Probiotics Are Not the Cause

In their recent study, Rao and colleagues1 incriminated probiotics in the induction of D-lactic acidosis (1). Many who benefit from probiotics could be frightened—on the basis of this report—into stopping them, with potentially negative impacts on their health (2). Some probiotic bacteria, including some specific components of the intestinal microbiota, may produce D-lactic acid. Indeed, if plasma D-lactic acid rises sufficiently, it is clinically relevant, causing D-lactic acidosis. D-lactic acidosis has mainly been observed in subjects with short bowel syndrome. However, some authorities have regulated the use of D-lactic acid producing bacteria in infant and weaning foods, but the reasoning for normal infant population has been debated. Even in adults, the safety of D-lactic acid producing bacteria has been challenged, but apart from short bowel patients no evidence on clinical problems has been reported (3).

For this reason, we conducted a review and examined whether D-lactic acid-producing bacteria, acidified infant formulas and fermented infant formulas were potential causes of paediatric D-lactic acidosis (4).

We identified five randomised controlled trials conducted between 2005-2017 with 544 healthy infants. Additionally, some case reports and experimental studies were considered. No clinically relevant adverse effects of D-lactic acid-producing probiotics or fermented infant formulas in healthy children were identified. The only known cases of paediatric D-lactic acidosis were observed in patients with short bowel syndrome (4). It is of importance that human milk also contains lactic acid bacteria and bifidobacteria, some of which may produce D-lactic acid. Some stress situations, such as exercise, may elevate human milk lactate concentrations.  Thus, breast milk D-lactate content needs to be analysed more carefully to compare with fermented infant formulas.

Taken together, our results suggest that neither the probiotics that were evaluated in the studies we reviewed nor fermented infant formulas cause D-lactic acidosis in healthy children.

 

  1. Rao, S. S. C., Rehman, A., Yu, S. & Andino, N. M. Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.  Transl. Gastroenterol.9, 162 (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006167/
  2. Sanders, M. E., Merenstein, D. & Merrifield, C. A. Probiotics for human use.  Bull.43, 212–225 (2018). https://onlinelibrary.wiley.com/doi/10.1111/nbu.12334
  3. Quigley E.M.M, Pot B., Sanders M.E. ‘Brain fogginess’ and D-lactic acidosis: probiotics are not the cause. Transl. Gastroenterol.9, 187 (2018). https://www.nature.com/articles/s41424-018-0057-9
  4. Łukasik, J., Salminen S., Szajewska H. Rapid review shows that probioticsand fermented infant formulas do not cause D-lactic acidosis in healthy children. Acta Pediatrica 107, 1322-1326 (2018). https://www.ncbi.nlm.nih.gov/pubmed/29603358

FDA/NIH Public Workshop on Science and Regulation of Live Microbiome-based Products: No Headway on Regulatory Issues

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

September 20, 2018

By Mary Ellen Sanders, PhD, Executive Science Officer, ISAPP

On September 16, 2018, the US Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER) and National Institute of Allergy and Infectious Diseases (NIAID) collaborated on the organization of a public workshop on “Science and Regulation of Live Microbiome-based Products Used to Prevent, Treat, or Cure Diseases in Humans”.  I was present at this meeting along with ISAPP vice-president, Prof. Daniel Merenstein MD, who lectured on the topic of probiotics and antibiotic-associated diarrhea.

Prof. Dan Merenstein speaking at CBER/NIAID conference

While regulatory issues are often discussed at other microbiome conferences, the fact that this meeting was organized by the FDA suggested it was a unique opportunity for some robust discussions and possible progress on regulatory issues involved with researching and translating microbiome-targeted products. The regulatory pathways to drug development seem clear enough, but regulatory issues for development of functional foods or supplements are less clear. Jeff Gordon and colleagues have previously pointed out regulatory hurdles to innovation of microbiota-directed foods for improving health and preventing disease (Greene et al. 2017), and at the 2015 ISAPP meeting, similar problems were discussed (Sanders et al. 2016).

The meeting turned out to be mostly about science. Some excellent lectures were given by top scientists in the field (see agenda below), but discussion about regulatory concerns was a minimal component of the day. Questions seeding the panel discussions focused on research gaps, not regulatory concerns: an unfortunate missed opportunity.

Bob Durkin, deputy director of the Office of Dietary Supplements (CFSAN), left after his session ended, suggesting he did not see his role as an important one in this discussion. One earlier question about regulatory perspectives on prebiotics led him to comment that the terms ‘probiotic’ and ‘prebiotic’ are not defined. From U.S. legal perspective he is correct, as there are no laws or FDA regulations that define these terms. But from a scientific perspective, such a statement is disappointing, as it shows the lack of recognition by U.S. regulators of the widely cited definitions developed by top researchers in these fields and published in 2014 and 2017, respectively.

Two issues not addressed at this meeting will require clarification from the FDA:

The first is how to oversee human research on foods or dietary supplements. CBER’s oversight of this research has meant most studies are required to be conducted under an Investigational New Drug (IND) application. From CBER’s perspective, these studies are drug studies. However, when there is no intent for research to lead to a commercial drug, the IND process is not relevant. Even if endpoints in the study are viewed as drug endpoints by CBER, there should be some mechanism for CFSAN to make a determination if a study fits legal functions of foods, including impacting the structure/function of the human body, reducing the risk of disease, or providing dietary support for management of a disease. When asked about this, Durkin’s reply was that CFSAN has no mechanism to oversee INDs. But the point was that without compromising study quality or study subject safety, it seems that FDA should be able to oversee legitimate food research without forcing it into the drug rubric. CBER acknowledged that research on structure/function endpoints is exempt from an IND according to 2013 guidance. But FDA’s interpretation of what constitutes a drug is so far-reaching that it is difficult to design a meaningful study that does not trigger drug status to them. For example, CBER views substances that are given to manage side effects of a drug, or symptoms of an illness, as a drug. Even if the goal of the research is to evaluate a probiotic’s impact on the structure of an antibiotic-perturbed microbiota, and even if the subjects are healthy, they consider this a drug study. With this logic, a saltine cracker eaten to alleviate nausea after taking a medication is a drug. Chicken soup consumed to help with nasal congestion is a drug. In practice, many Americans would benefit from a safe and effective dietary supplement which they can use to help manage gut disruptions. But in the current regulatory climate, such research cannot be conducted on a food or dietary supplement in the United States. There are clearly avenues of probiotic research that should be conducted under the drug research oversight process. But for other human research on probiotics, the IND process imposes research delays, added cost, and unneeded phase 1 studies, which are not needed to assure subject safety or research quality. Further, funders may choose to conduct research outside the United States to avoid this situation, which might explain the low rate of probiotic clinical trials in the United States (see figure).

The second issue focuses on actions by CBER that have stalled evidence-based use of available probiotic products. This issue was discussed by Prof. Merenstein in his talk. He pointed out that after the tragic incident that led to an infant’s death from a contaminated probiotic product (see here; and for a blog post on the topic, see here), CBER issued a warning (here) that stated that any probiotic use by healthcare providers should entail an IND. This effectively halted availability of probiotics in some hospital systems. For example, at Johns Hopkins Health-system Hospitals, the use of probiotics is now prohibited (see below). Patients are not allowed to bring their own probiotics into the hospital out of concern for the danger this poses to other patients and staff. This means that a child taking probiotics to maintain remission of ulcerative colitis cannot continue in the hospital; an infant with colic won’t be administered a probiotic; or a patient susceptible to Clostridium difficile infection cannot be given a probiotic. Available evidence on specific probiotic preparations indicates benefit can be achieved with probiotic use in all of these cases, and denying probiotics can be expected to cause more harm than benefit.

It might be an unfortunate accident of history that probiotics have been delivered in foods and supplements more than drugs. The concept initially evolved in food in the early 1900’s, with Metchnikoff’s observation that the consumption of live bacilli in fermented milk had value for health. Probiotics have persisted as foods through to the modern day, likely because of their safety. The hundreds of studies conducted globally, including in the U.S. until 10-15 years ago, were not conducted as drug studies, even though most would be perceived today as drug studies by CBER. This has not led to an epidemic of adverse effects among study subjects. True, serious adverse events have been reported, but the overall number needed to harm due to a properly administered probiotic is negligible.

According to its mission, the FDA is “…responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health.” Forcing human research on products such as yogurts containing probiotics to be conducted as drug research, when there is no intent to market a drug and when the substances are widely distributed commercially as GRAS substances, does not advance this mission. Further, CBER actions that discourage evidence-based use of available probiotics keeps effective and safe products out of the hands of those who can benefit.

A robust discussion on these issues was not part of the meeting earlier this week.  Researchers in the United States interested in developing probiotic drugs will find CBER’s approaches quite helpful. Yet researchers interested in the physiological effects of, or clinical use of, probiotic foods and supplements will continue to be caught in the drug mindset of CBER. CFSAN does not seem interested. But without CFSAN, human research on, and evidence-based usage of, probiotic foods and supplements will continue to decline (see figure), to the detriment of Americans.

Human clinical trials on “probiotic”
1992-September 20, 2018

 

 

 

Clinical evidence and not microbiota outcomes drive value of probiotics

/in featured, News /by Mary Ellen Sanders

By ISAPP Board of Directors, plus Prof. Francisco Guarner and Dr. Bruno Pot

September 10, 2018

Two recent papers have generated much adverse publicity for the probiotic field. Headlines driven by sensationalism, not data, claim “Probiotics labelled ‘quite useless’” (BBC) and “Probiotics ‘not as beneficial for gut health as previously thought’” (The Guardian). The quotes are from author Eran Elinav, who generalizes the study findings to all ‘probiotics’ as a class – a generalization that ignores that specific probiotic are meant for specific purposes. This research was published this month in Cell (here and here).

The scope of these papers is limited to microbiome data; no clinical endpoints are assessed. Without clinical evidence, it is not possible to conclude about the tested probiotic’s usefulness, and it is certainly not possible to conclude about probiotic usefulness in general. Stating that probiotics are ‘quite useless’ or ‘not as beneficial’ is, quite simply, wild and factually inaccurate. The authors discount the existing body of evidence for probiotic health benefits, including Level 1 placebo-controlled, randomized trials. Cochrane reviews (the gold standard used by physicians and public health policy makers) of the totality of evidence show that specific probiotics can prevent antibiotic associated diarrhea (AAD) and C. difficile diarrhea. This evidence has been translated into evidence-based recommendations for probiotics issued by medical groups. Regardless of an effect on the microbiota, these are established, evidence-based benefits of probiotics.

No clinical endpoints tracked in either study

What these papers provide is extensive data about the impact of one product containing 11 common probiotic species on different microbiome measures. To the authors’ credit, they analyzed mucosal and luminal samples from humans, in addition to samples from stool.  Nonetheless, the probiotic definition [live microorganisms that, when administered in adequate amounts, confers a health benefit on the host (Hill et al 2014)] does not require that probiotics function via interaction with the microbiota, nor is there much evidence that they alter the microbiota composition in an appreciable manner. Absence of impact on microbiome measures is not evidence that probiotics lack clinical or physiological effects. Probiotics function via many mechanisms that might not be revealed by the measures made in these papers.

Methodological concerns

A careful reading of this paper reveals many methodological concerns.

The extensive data in the paper is an assortment of different types of analyses. For example, for a beta-diversity metric, they sometimes use weighted Unifrac, sometimes unweighted Unifrac, and sometimes Bray-Curtis, without an explanation for their choice. These approaches to presenting the data can give very different results. With the transcriptomics data, sometimes the authors choose samples from the duodenum and sometimes the jejunum. For example, in figure 6, panels C-E compare the difference in gene expression between the naïve group and the treatment in the duodenum, whereas in panels F-H they compare the antibiotic state with the treatment in the jejunum. Such an approach leads the reader to speculate that the authors picked the metrics and data that best fitted the story they wanted to tell. In a well-conducted clinical trial, the statistical plan is registered before the study starts, to assure readers that the scientific process of advancing a hypothesis and designing a study to test the hypothesis is respected.

The probiotic was not administered to human subjects until 7 days after the treatment with antibiotics commenced, after the damage by the antibiotics has been done. Dozens of human studies with specific probiotics have documented that probiotics prevent AAD or C. difficile infection. In most clinical trials, the probiotic is administered together with the antibiotics. A recent meta-analysis concluded that “administration of probiotics closer to the first dose of antibiotic reduces the risk of (Clostridium difficile infection) by >50% in hospitalized adults.” (Emphasis added) The approach in the Suez et al paper is not consistent with the aforementioned clinical studies, with how probiotics are used in clinical practice or with the knowledge of how probiotics most likely prevent AAD. When provided on the same days as antibiotics, probiotics have the opportunity to prevent overgrowth of opportunistic, antibiotic-resistant microbes by competitive exclusion in the ecosystem. Therefore, the microbiome findings of Suez et al likely cannot be applied to clinical trials with such different time course of antibiotic/probiotic administration.

Several conclusions about the effect of probiotics on the microbiota were based on relative abundance measures, which do not relate to actual bacterial numbers or metabolic activity of all relevant species in the gut.

The antibiotic treatment used was potent for a study population that would otherwise not need antibiotics. Volunteers were administered oral ciprofloxacin 500 mg bi-daily and oral metronidazole 500 mg tri-daily for a period of 7 days. They are both very strong and indiscriminate antibiotics, having a severe impact on the gut microbiota.  One could question if this drug therapy might have a different impact on the microbiome of a healthy person compared to a patient likely to receive this treatment, i.e., one whose microbiota ecosystem is disrupted by disease or fever.

The probiotic product

A serious issue is that the authors chose a product for this study that has no demonstrated clinical benefits. At a minimum, the product used for this study should have evidence for impact on antibiotic associated conditions, including symptoms or emergence of opportunistic pathogens. The 3 (possibly 2, as the latter 2 appear to be the publication of the same data) human studies conducted on this product (here, here and here), showed no clinical benefit. Thus, the investigators tested the potential benefits of a product for which no benefits had been previously shown. Further, the papers do not adequately describe the product; only a total count (25 billion) is given; counts of each strain – through the end of the administration period – should have been provided. Furthermore, the authors state about the product that “B. longum was probably represented by two strains.” This constitutes imprecise characterization unacceptable in a well-defined probiotic product.

Appearance of author bias

The conclusions reached in the papers promote a personalized approach to probiotic use. In an article on the BBC, the lead author stated, “In the future probiotics will need to be tailored to the needs of individual patients. And in that sense just buying probiotics at the supermarket without any tailoring, without any adjustment to the host, at least in part of the population, is quite useless.” The authors did not disclose they are involved with a company promoting this personalized approach.

Probiotic colonization

The authors suggest that their finding that probiotics do not colonize long term is noteworthy. In fact, researchers in this field have known this for 30 years: most probiotics do not colonize or become established as part of the resident microbiota. A 2016 paper by Madonado-Gomez et al was notable precisely because a Bifidobacterium longum strain was found that did persist. In most cases, probiotic effects are likely mediated by transient effects.

Responders and non-responders

A well-established concept in medicine is that some people respond clinically and physiologically to interventions and others don’t. This is the case with much of probiotic as well as pharmaceutical literature. (See review on responders and non-responders to probiotics by Reid et al.) An individual’s response is likely impacted by diet, resident microbes, host genes and host physiology/health. The validity of a personalized approach to probiotic administration remains to be determined, as evidence for a clinical benefit to the approach is needed. Microbiome data alone are not sufficient.

Need for future research

In the Cell publications, the authors acknowledge their study was limited due to lack of clinical endpoints and the testing of only a single product. It is unfortunate that the press marched ahead with inflammatory stories about the negative effects of probiotics based on such paltry evidence. The scientific community understands that this is one study, on a small number of human subjects, by one research group. Sweeping conclusions cannot be made. There are many hypotheses that can be generated from this study that can lead to follow up studies, which we hope will ensue.

Conclusions

Hundreds of human trials have demonstrated clinical benefits of probiotics and several evidence-based recommendations have been issued by medical organizations. Of course, not all studies are positive. Not all probiotics work for all conditions. But the safety record of probiotics administered to healthy as well as many patient populations is well-established. Numerous media outlets have reported on these two studies as if they are proof that probiotics are useless at best and harmful at worst. This irresponsible reporting may lead people who are benefitting from probiotics to stop using them, potentially causing real harm.

The erroneous interpretation of the current study and previous research by the primary author is disingenuous, as he states,  “Contrary to the current dogma that probiotics are harmless and benefit everyone, these results reveal a new potential adverse side effect of probiotic use with antibiotics that might even bring long-term consequences.” This comment and the papers’ conclusions are not corroborated by the totality of safety and efficacy clinical evidence on probiotics, which includes thousands of probiotic-treated subjects. In comparison, the data in Suez et al come from microbiome assessments from only eight probiotic-treated subjects.

Furthermore, this paper evaluated just one product of limited provenance and containing a combination of multiple, incompletely characterized strains. This is in sharp contrast to numerous studies of precisely characterized strains demonstrating well-defined and beneficial engagements with the host. Zmora and colleagues and Suez and colleagues are to be congratulated on their attempts to characterize in detail the impact of one probiotic product on a perturbed, human microbiome. We look forward to further such studies employing well-characterized strains with demonstrated clinical benefits and including relevant clinical endpoints.

Additional reading:

Risk assessment of probiotics use requires clinical parameters

ISAPP comments: International Group of Probiotic Scientists Weighs in on Flawed Conclusions From New Scientific Papers

American Gastroenterological Association response: AGA’s Interpretation of the Latest Probiotics Research

Response by Prof. Gregor Reid:  Trying to Close the Stable Door After the Horse Has Bolted

cber

CBER to hold public workshop on regulation of biologics

/in featured, News /by Mary Ellen Sanders

FDA’s Center for Biologics Evaluation and Research (CBER) is convening a public workshop Sept 17 in Rockville MD on the Science & Regulation of Live Microbiome-Based Products Used to Prevent, Treat, or Cure Diseases in Humans. It is now open for registration (free). See here for the program and here for additional info.

The evidence for efficacy, the safety and the regulatory framework for probiotics other live microbiome based products will be discussed. Prof. Dan Merenstein MD, ISAPP’s current Vice President, will speak on evidence, research and clinical use of probiotics for antibiotic associated diarrhea. Although the title suggests the meeting will focus on drugs, Dr. Bob Durkin from the Center for Food Safety and Applied Nutrition (CFSAN) of the FDA will speak on probiotic foods and dietary supplements.

This workshop is an opportunity for stakeholders to share with FDA and NIH concerns regarding the regulatory approach to probiotics adopted by the FDA. The path for development of probiotic drugs is reasonably clear. But the road to develop probiotic foods, supplements or microbiome-based dietary strategies to compensate for deficient microbiota is less so. These products are intended to improve gut function, nutritional status, immune status, metabolic properties and more. These are legal functions for foods and supplements, but the FDA doesn’t seem to see it that way.

The FDA has for the most part has approached probiotics as drugs (Sanders et al. 2016). Since probiotics are live microbes, and since CBER deals with drugs that are derived from living sources, CBER often oversees human research on probiotics. But there is no mechanism within CBER to oversee foods and supplements, and hence, human research on probiotics tends to be shunted into the investigational new drug (IND) process. But, the legal definitions of drugs and foods overlap – both can impact the structure/function of the human body and both can reduce the risk of disease. So conducting such research on probiotic foods – and not as part of the IND rubric – should be possible. Perhaps progress on this front can be achieved in the CBER workshop in September.

In a press announcement, FDA Commissioner Scott Gottlieb MD shared FDA perspective on probiotics and promoted this CBER conference. A couple of issues are noteworthy in this announcement by Gottlieb. First, the term ‘probiotic’ is used. Over the years, the FDA largely avoided use of this term, instead favoring the term live biotherapeutic product (LBP). But these terms are not synonymous. Probiotic is defined as a live microorganisms that, when administered in adequate amounts, confers a health benefit on the host (Hill et al. 2014). It spans multiple regulatory categories. A LBP is by definition a drug. The fact that Gottlieb used the term ‘probiotic’ may signal that he recognizes that not all probiotics are drugs. Second, Gottlieb’s announcement shows awareness that probiotics are legitimate components in foods and dietary supplements and states that the FDA is “committed to working with industry on efforts to provide information that can help consumers make more informed choices about these products.” This is a welcome statement to many researchers involved in probiotic foods and supplements in the United States. It suggests that the FDA is willing to look beyond probiotics as LBPs and develop regulatory approaches for research and claims appropriate to foods and supplements.

Innovation in this field, which has the potential to benefit many people globally, requires regulatory approaches that do not obstruct. Participation in this workshop may lead to improvements that both protect public safety and facilitate academic and industry researchers in the United States on the path to discovery.

 

Additional information:

Sanders ME, Shane AL, Merenstein DJ. Advancing Probiotic Research in Humans the United States: Challenges and strategies. Gut Microbes 7(2):97-100.

Warning letter from CBER: Dietary Supplements Containing Live Bacteria or Yeast in Immunocompromised Persons: Warning – Risk of Invasive Fungal Disease. Posted 12/09/2014.

blog reid elderly

Do dietary effects on gut microbiota promote health in older individuals? Reid and colleagues gain insights into microbiota composition across the lifespan

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

January 22, 2018. By Dr. Gregor Reid

ISAPP Board of Directors member Dr. Gregor Reid recently co-authored a cross-sectional study in a cohort of over 1000 very healthy Chinese participants from 3 to over 100 years of age in order to gain insights on ‘healthy’ microbiota composition and whether this changes with age. Using next-generation sequencing (Illumina MiSeq platform) and large-scale compositional data analysis techniques, the study demonstrated that there was very little difference in the fecal microbiota composition of individuals between the around 30 years of age and around 100—as long as the individuals were extremely healthy.

The concept of consuming live microorganisms that offer a benefit to the host (probiotics), or a substrate that is selectively utilized by host microorganisms conferring a health benefit (prebiotics), to promote health in aging populations is becoming more popular. However, it is not currently known what constitutes a ‘healthy’ gut microbiota composition, or what specific prebiotic/probiotic might help establish it.

Discussing the study results in a Reddit Ask Me Anything session, Reid explains, “It is hard to pin down outcomes to one factor such as food, and which components of those foods are critical, but seeing the super-healthy elderly having the same microbiota profile as the super-healthy young adult might make us see if some food practices from 75 years ago have returned.”

Although the study design (cross-sectional) does not allow for a cause and effect relationship to be established, the results may signify that the similarity of gut microbes across ages is a consequence of an active lifestyle and good diet—in contrast with previous hypotheses that aging per se affected gut microbiota composition. Based on these findings, it is reasonable to hypothesize that reestablishing a dysbiotic microbiota composition in older adults, to mirror that of a 30-year-old, may promote health. Moreover, the results offer an established baseline microbiota composition by which other cohorts with chronic or acute disease may be compared.