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Episode 27: Investigating the benefits of live dietary microbes

/in Podcast, Season Two /by Laura

 

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The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Investigating the benefits of live dietary microbes, with Prof. Colin Hill PhD and Prof. Dan Tancredi PhD

Episode summary:

In this episode, the ISAPP podcast hosts themselves are the experts: Prof. Colin Hill PhD from APC Microbiome Ireland / University College Cork and Prof. Dan Tancredi PhD from University of California – Davis talk about their recent work investigating the health benefits from consuming higher quantities of live dietary microbes – and not just microbes that meet the probiotic criteria.

Key topics from this episode:

  • Profs. Hill and Tancredi were involved with others in a recent series investigations & 3 published papers on whether there should be a recommended daily intake of live microbes.
  • Prof. Hill started by writing a blog, prompted by the finding that meta-analyses on probiotics tended to show some general benefits for health. Would this apply to any safe, live microbes – even those that do not meet the probiotic criteria?
  • Various hypotheses (hygiene hypothesis, old friends hypothesis, missing microbes hypothesis) posit that a lack of microbes is associated with poorer health.
  • Clean water and clean food have reduced the burden of infectious disease. But at the same time, across populations there has been an increase in chronic diseases. Could a lack of live dietary microbes be contributing to this increase in chronic disease, because the immune system lacks adequate inputs? Or in other words, could there be a general health benefit for healthy people in consuming high quantities of live microbes?
  • To address the hypothesis scientifically: they investigated the health status of people who eat large vs. small numbers of safe live microbes in their diets. Starting with NHANES data in the US, the researchers classified foods into categories of high / medium / low numbers of live microbes.
  • Note that not all fermented foods contain live microbes, but some contain high numbers of live microbes. A possible confounding factor in the analysis was that high microbe foods tend to be healthier foods.
  • The researchers published a series of 3 papers. The 3rd paper showed an association between intake of live microbes and various (positive) measurements of health. Consistent, modest improvements were seen across a range of health outcomes.
  • This is an association, but statistically the team did use regression analysis to statistically adjust for effects on health that could be due to other factors besides the live microbial intake.
  • The take-home is not to eat unsafe or rotten food, but rather to eat more high-microbe or fermented foods, and in general eat a healthy diet.

Episode links:

Additional Resources:

Live Dietary Microbes: A role in human health. ISAPP infographic.

About Prof. Colin Hill PhD:
Colin Hill has a Ph.D in molecular microbiology and is a Professor in the School of Microbiology at University College Cork, Ireland. He is also a founding Principal Investigator in APC Microbiome Ireland, a large research centre devoted to the study of the role of the gut microbiota in health and disease. His main interests lie in the role of the microbiome in human and animal health. He is particularly interested in the effects of probiotics, bacteriocins, and bacteriophage. In 2005 Prof. Hill was awarded a D.Sc by the National University of Ireland in recognition of his contributions to research. In 2009 he was elected to the Royal Irish Academy and in 2010 he received the Metchnikoff Prize in Microbiology and was elected to the American Academy of Microbiology. He has published more than 600 papers and holds 25 patents. More than 80 PhD students have been trained in his laboratory. He was president of ISAPP from 2012-2015.

About Prof. Dan Tancredi PhD:
Daniel J. Tancredi, PhD, is Professor in Residence of Pediatrics in the University of California, Davis School of Medicine. He has over 25 years of experience and over 300 peer-reviewed publications as a statistician collaborating on a variety of health-related research. A frequent collaborator on probiotic and prebiotic research, he has attended all but one ISAPP annual meeting since 2009 as an invited expert. In 2020, he joined the ISAPP Board of Directors. Colin Hill and Daniel co-host the ISAPP Podcast Series “Science, Microbes, and Health”. On research teams, he develops and helps implement effective study designs and statistical analysis plans, especially in settings with clusters of longitudinal or otherwise correlated measurements, including cluster-randomized trials, surveys that use complex probability sampling techniques, and epidemiological research. He teaches statistics and critical appraisal of evidence to resident physicians; graduate students in biostatistics, epidemiology, and nursing; and professional scientists. Dan grew up in the American Midwest, in Kansas City, Missouri, and holds a bachelor’s degree in behavioral science from the University of Chicago and masters and doctoral degrees in mathematics from the University of Illinois at Chicago. He lives in the small Northern California city of Davis, with his wife Laurel Beckett (UC Davis Distinguished Professor Emerita), their Samoyed dogs Simka and Milka, and near their two grandkids.

Episode 26: The role of microbes in gut-brain communication

/in Podcast, Season Two /by Laura

 

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Google Podcasts | Spotify | RSS

The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

The role of microbes in gut-brain communication, with Prof. Emeran Mayer MD

Episode summary:

In this episode, ISAPP podcast host Prof. Dan Tancredi PhD welcomes guest Prof. Emeran Mayer MD, a gastroenterologist and researcher at University of California Los Angeles. They talk about the microbiota-gut-brain axis, covering its evolutionary origins and how this complex system works in the human body to support overall health.

Key topics from this episode:

  • Microbiota-gut-brain communication has a long evolutionary history: microbes have been around for billions of years and they stored a lot of information in their genes. At some point in evolution microbes got inside the digestive tube of a primitive marine animal called hydra and it proved advantageous for this animal.
  • The hydra shows the origin of the human enteric nervous system (ENS): microbes live inside this tube and transfer genes to the nerve cells of this digestive tube, showing the origin of neurotransmitters.
  • Today in humans the neurotransmitters influence gene expression of microbes and change the microbial behaviors; the metabolites produced feed back to the brain.
  • Prof. Mayer’s initial interest as a gastroenterologist was the ENS and how it regulates motility. Subsequently the ENS was found to regulate many gut functions. The gut also houses a large part of the immune system and a complex hormonal system, and all these systems are connected with each other and communicate with the brain.
  • There is an increasing understanding that many chronic diseases relate to Inappropriate engagement of the immune system, starting in the gut.
  • When Prof. Mayer started in the field, the term “gut health” did not exist. Now it’s a ubiquitous term which has associations with wellbeing, acknowledging the gut has influence on many other body systems.
  • The associations between gut (microbiota) and brain health started with provocative animal experiments from Cork, Ireland, in which researchers manipulated the gut microbiome and found changes in emotion-like behaviors of animals. However, it has been difficult to translate to human interventions.
  • How do microbiome-targeted dietary interventions affect the brain? We do know the “Standard American Diet” (deficient in fiber) has changed the gut microbes in a way that compromises the production and maintenance of the gut barrier. 
  • There are many misconceptions about “leaky gut”, but basically contact between beneficial microbes and immune system sensors stimulate the immune system of the gut to low-grade inflammation. This can alter the tight junctions, making the gut more permeable, and ultimately this can affect the brain. Diet can affect the role of microbes in maintaining an effective gut barrier.
  • Prof. Mayer describes how he ended up studying the microbiota-gut-brain axis – he would not have predicted how important and popular this field would become.
  • In the future, there will be more sophisticated and personalized interventions. He sees a paradigm shift happening from reductionist approaches in medicine to systems biological approaches. This field is making us acknowledge that diet will play a major role.

Episode links:

About Prof. Emeran Mayer MD:

Emeran A Mayer is a Gastroenterologist, Neuroscientist and Distinguished Research Professor in the Department of Medicine at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress & Resilience and Founding Director of the Goodman Luskin Microbiome Center at UCLA. He is one of the pioneers and leading researchers in the bidirectional communication within the brain gut microbiome system with wide-ranging applications in intestinal and brain disorders. He has published 415 scientific papers, co edited 3 books and has an h-index of 125. He published the best selling books The Mind Gut Connection in 2016, the Gut Immune Connection in June 2021, and the recipe book Interconnected Plates in 2023. He is currently working on a MasterClass and a PBS documentary about the mind gut immune connection. He is the recipient of numerous awards, including the 2016 David McLean award from the American Psychosomatic Society and the 2017 Ismar Boas Medal from the German Society of Gastroenterology and Metabolic Disease.

What does “gut health” mean?

/in Consumer Blog /by KC

By Prof. Maria Marco PhD, University of California – Davis

Probiotics and prebiotics are frequently marketed to consumers for their capacity to improve or support gut health. Dietitian nutritionists responding to a survey ranked fermented foods as the top superfood for the past six years explaining gut health as a primary reason for their choice. But what is gut health exactly?

As it turns out, there is not a widely accepted definition of gut health. Dr. Stephan Bischoff at the University of Hohenheim, Germany, nicely summarized the situation in a perspective back in 2011. Using criteria from the World Health Organization, he proposed that gut health be defined as “a state of physical and mental well-being in the absence of gastrointestinal complaints that require the consultation of a doctor, in the absence of indications or risks of bowel disease, and in the absence of confirmed bowel disease”. The term gut health has since been increasingly used in scientific publications. However, is gut health really only the absence of complaints or indications, risk, or disease? Is gut health a condition that requires physical and mental well-being?

For the first question, it seems reasonable that gut health would refer to an absence of bowel diseases and acute or even mild symptoms localized to the digestive tract such as food intolerance, abdominal pain, nausea, flatulence, bloating, constipation, and diarrhea. The etiology of these presentations can be traced back to disruptions in the normal functioning of the gastrointestinal tract, including undesired dietary nutrient breakdown and absorption, pathogen introduction and colonization, and intestinal inflammation. However, recent studies of the intestinal environment, encompassing both the intestinal microbiome and mucosa, suggest that an absence of complaints or disease does not directly mean our gut is healthy. Mild mucosal inflammation, increased barrier permeability, or the presence of certain potentially undesirable intestinal microorganisms may confer no overt symptoms, yet still could signify the presence of an undesired or unhealthy intestinal state. The outcomes of that imperceptible unhealthy state may not be realized until years later with the development of intestinal disease or conditions at extraintestinal sites.

This latter point evokes the second question: Is gut health a condition that requires physical and mental well-being? The answer from popular media is – yes! Diseases and chronic conditions that are not overtly related to the gastrointestinal tract, such as allergy, arthritis, obesity, cancer, mood disorders and depression, are now considered by many to be traceable back to gut health. To that regard, it is now well-established scientifically that our gastrointestinal tract is indeed an important organ, housing the majority of our microbiome and mucosal immune system and pivotal for systemic metabolism and neurological signaling. However, I wonder if the term “gut health” is at all appropriate when implying such a broad range of whole-body responses? Could it be that “gut health” is seen as the root or origin of our overall health?

One way to reconcile this broad interpretation of gut health is to consider that “gut health” has become a simple way to explain, interpret, and understand how diets intersect with overall physical and mental well-being. Our daily lives are structured around mealtimes and the foods we eat don’t just provide nutrients, but also social interactions, and can be affected by our socioeconomic status among many other factors. We connect our gut with sensations felt when hungry, full, and after drinking an alcoholic or caffeinated beverage. The gut also connects to diet-based risks for the development of non-communicable diseases over our lifetimes. The quote “all diseases begin in the gut” attributed to Hippocrates still rings true after all the medical advancements over the past 2400 years.

So, since the term “gut health” has such a broad interpretation, we should be qualifying any statement that a biotic or fermented food supports “gut health” with an explanation for the specific feature(s) of gut health that are being improved with biotic use. Perhaps in the future, good gut health, and even good health generally, can be defined. Until then, we only appreciate how we are starting to get closer to understanding the true interconnectedness of the diet-gut-microbiome axis with our overall health and well-being.

 

 

Episode 23: Studying microbial ecosystems and how they support health

/in Podcast, Season Two /by Laura

 

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Google Podcasts | Spotify | RSS

The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Studying microbial ecosystems and how they support health, with Prof. Emma Allen-Vercoe PhD

Episode summary:

In this episode, the ISAPP podcast hosts talk about microbial ecosystems with Prof. Emma Allen-Vercoe PhD from the University of Guelph in Canada. Prof. Allen-Vercoe describes how her lab brings together information from microbial sequencing and culturing to learn about the human gut microbiome and how it supports health. She discusses what we know about the industrialized gut microbiome and possible ways to improve health by manipulating it.

Key topics from this episode:

  • What the microbiome is and the suite of tools that are typically used to study it.
  • Allen-Vercoe does both sequencing and culturing in her lab as well as metabolomics, proteomics, and transcriptomics to discover on a molecular level at what the microbes are doing. They have a model system called “Robogut” to study microbial ecosystems.
  • Culturing is still crucial and it’s important for trainees in microbiology to gain experience culturing organisms that are less straightforward to grow. The late Sydney Finegold inspired others to try culturing more challenging microorganisms.
  • The challenge of culturing is matching the techniques in the lab to what happens in nature when it grows. Her lab builds metagenome-associated genomes to be able to predict the particular substrates that a certain microbe needs to grow.
  • The “missing microbes” hypothesis is that the human microbiome has been depleted over a few generations in people from industrialized societies, and this correlates with an increase in chronic diseases.
  • The Yanomami people from South America have very diverse gut microbiomes and they share certain species with other non-industrialized societies very distant from them around the world, which are not found in industrialized populations. People in industrialized societies are never exposed to these microbes, but even if they were, the microbes might not stick around because the substrates needed to sustain them  (e.g. through the diet) are absent. 
  • The industrialized microbiome is not necessarily ‘bad’ but we do have to find out more about whether the lack of certain microbes has health effects. This is possible through the Robogut system, which can perturb microbial ecosystems and look at their behavior without affecting people’s health.
  • Fecal transplants have limitations, so they’ve started to work on therapeutic ecosystems. These are “clean” or defined ecosystems that can be administered therapeutically.

Episode links:

About Prof. Emma Allen-Vercoe PhD:

Emma obtained her BSc (Hons) in Biochemistry from the University of London, and her PhD in Molecular Microbiology through an industrial partnership with Public Health England. Emma started her faculty career at the University of Calgary in 2005, with a Fellow-to-Faculty transition award through CAG/AstraZeneca and CIHR, to study the normal microbes of the human gut. In particular, she was among the few that focused on trying to culture these ‘unculturable’ microbes in order to better understand their biology. To do this, she developed a model gut system to emulate the conditions of the human gut and allow communities of microbes to grow together, as they do naturally. Emma moved her lab to the University of Guelph in late 2007, and has been a recipient of several Canadian Foundation for Innovation Awards that has allowed her to develop her specialist anaerobic fermentation laboratory further. This has been recently boosted by the award of a Tier 1 Canada Research Chair in Human Gut Microbiome Function and Host Interactions. In 2013, Emma co-founded NuBiyota, a research spin-off company that aims to create therapeutic ecosystems as biologic drugs, on a commercial scale. The research enterprise for this company is also based in Guelph.

Supercharging innovation: New session at ISAPP 2023 annual meeting brings industry and student members together to scientific innovation workshop in the field of biotics

/in News /by KC

Innovation in the biotics field is an important way to address some of our most important challenges in health, and ISAPP is the organization on the forefront of this innovation. This year ISAPP members are excited to debut a new workshop focused on innovation, June 26th at the 2023 ISAPP annual meeting in Denver. For this workshop, the Industry Advisory Committee (IAC) and the Students and Fellows Association (SFA) have joined forces and initiated a new way to share knowledge and promote networking opportunities.

How did the idea of the IAC-SFA innovation workshops come about?

The Innovation Workshops evolved from interest in how SFA and IAC might gain scientific insights from each other. What they have in common is a dedication to cutting-edge science. From this emerged the idea that these groups could convene several concurrent workshop sessions during the pre-meeting program focusing on innovation in the biotic field.

What will be discussed at the workshops?

The concurrent workshops will focus on four topics:

  • Innovation in prebiotics: What’s next? Chaired by Marla Cunningham
  • Latest advances in microbiome models and biotic screening techniques. Chaired by Brendan Daisley
  • Looking to the future for food and biotics. Chaired by Daragh Hill
  • Probiotic application beyond the gut: What have we learned and what’s next? Chaired by Mariya Petrova

Guided by IAC and SFA representatives, the attendees at each workshop will discuss topics of interest and attempt to answer relevant questions in the biotics field. For example:

  • What are the latest developments in the biotic field regarding research, discoveries, and techniques?
  • What problems are we currently facing, and how will we solve them?
  • What are the future opportunities, and how can we progress?

How will this advance innovation in the field?

The Innovation Workshops will provide a platform where IAC representatives and SFA members can benefit from the exchange ideas gained from unique viewpoints expressed. Industry members can hear firsthand about innovative research that students and fellows perform in their labs, while students can gain a deeper understanding of some of the considerations for commercialization and opportunities and barriers in the marketplace. By joining forces, we believe these workshops will form a bridge between industry and young generation scientists and provide valuable insights into to the latest biotic questions.

Through initiatives such as these, ISAPP drives scientific innovation in biotics for the benefit of the entire field.

Popular media, misinformation and ‘biotics’

/in News /by KC

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

Encountering misinformation is all too easy when seeking understanding of probiotics, prebiotics, synbiotics, and postbiotics (collectively, ‘biotics’). It can be perpetuated both by proponents and detractors. Through this lens, I’m prompted to comment on some high profile pieces making news recently. A Washington Post article Probiotic supplements may do the opposite of boosting your gut health was published on March 28, 2023, by Anahad O’Connor. This author was then interviewed for a CBS video story Studies find that probiotics can harm gut health on March 30, 2023.  Then, a National Geographic article Probiotics, prebiotics, postbiotics. What’s the difference? was published on the same day.

These pieces appropriately acknowledge the availability of evidence linking probiotics to human benefits. Yet the points raised about potential harms from probiotics and a misunderstanding of what ‘biotic’ substances really are deserve comment.

Harms of probiotics

Amid a backdrop of marketing and media messaging lauding the many benefits of probiotics, reporters are understandably drawn to the counter message that ‘probiotics can harm gut health’. Safety must always be rigorously assessed, as encouraged by a 2023 ISAPP paper focused on emerging issues in probiotic safety (see here). However, the claims of harm made – although generated from studies in humans – are not based on clinical endpoints. Instead they are based on either microbiome endpoints (Suez et al. 2018) or on post hoc analysis of biomarker outcomes (Wastyk et al. 2023). The limitations of the Suez et al. 2018 study were discussed in more detail previously (See: Clinical evidence and not microbiota outcomes drive value of probiotics). This paper evaluated the effect of one multi-strain probiotic product and is the only paper I am aware of that shows that probiotics inhibit microbiome recovery after antibiotic treatment. The paucity of supporting evidence for the harm supposedly documented in this paper is not mentioned in the stories. It is noteworthy that in the Wastyk et al. 2023 paper the authors acknowledge that the study did not achieve its primary objectives, and in referring to their post hoc analysis (including the ‘evidence’ for harm), they specifically acknowledge that such analysis is not conclusive evidence:  “We next leveraged aspects of our study design … in a discovery analysis process to reveal trends that could inform possible … hypotheses for future studies.” These studies are best used for generating hypotheses requiring further study.

Another criticism that was leveraged as evidence that probiotics cause harm is that probiotics reduce microbiota diversity. Any probiotic-induced reduction in diversity of fecal microbiota has not been shown to be associated with harm. Further, most studies show no significant overall changes in microbiome composition in response to traditional probiotic administration. However, it should be understood that the value of diversity as a marker of health remains unproven. The evidence is from observational studies and only shows associations, not causality.

 You can’t both object to criticisms based only on microbiome data but then promote probiotics based on it.

As stated, relying on microbiota endpoints to advance the idea that probiotics cause harm is not justified. But I cannot escape the fact that probiotic proponents in part contribute to this thinking. When probiotics are marketed as being able to ‘balance the microbiota’, without clinical data to substantiate a benefit, aren’t they promoting the same limited science?

Adherence to definitions of biotics needed

ISAPP has rigorously considered and offered definitions for probiotics, prebiotics, synbiotics, postbiotics and fermented foods (see here for a summary), which have been presented in highly cited reviews in Nature Reviews Gastroenterology and Hepatology (see here, here, here, here and here). These efforts were undertaken to advance a common understanding of these terms, so that precision can be attained in communications on them.

This objective has been far from realized. Misuse of these terms continues on product labels, in scientific publications, and in popular press communications.

The articles cited above compelled me to offer some take home messages for those responsible for accurately communicating science:

  • “Prebiotics + probiotics = postbiotics”, a heading in the National Geographic article, is completely wrong.

Probiotics are: Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host

Prebiotic is: A substrate that is selectively utilized by host microorganisms conferring a health benefit on the host

Postbiotic is: Preparation of inanimate microorganisms and/or their components that confers a health benefit on the host

  • Fermented foods are not the same as probiotics. Most fermented foods have not been proven to improve health (associative studies have suggested, but in most cases not proven, health benefits), many do not retain live microbes, and most are not made with microbes characterized to the strain level. All these are requirements to meet the definition of a probiotic. See here, here and here for clear discussions of this issue.
  • Fermented foods are not the magic bullet that many portray them as. Yes – for that subset of fermented foods that retain live microbes – they may contribute a diversity of live microbes to the diet. ISAPP has recently researched this area (see recent ISAPP publications here and here). And yes, they are tasty. However, the evidence level for benefits of traditional fermented foods is nowhere near the level for probiotics. Still, healthcare professionals critical of evidence supporting probiotic benefits commonly recommend fermented foods.
  • Postbiotics do not refer to ‘metabolites from probiotics’. See here for why ISAPP focused the definition of postbiotic on inactivated microbes with or without their metabolites.
  • In simplistic language, prebiotics can be viewed as food for beneficial microbes, but, typically, prebiotics target the normal microbes in the gut, not probiotics. See here.

Conclusion

Both the positive and negative effects of probiotics based on microbiome assembly can be misrepresented in the press, by some marketing claims, and sometimes in scientific literature. The field will benefit from communications that acknowledge the limitations of available science. Further, it’s important for clarity in communication that the field coalesces around established definitions and honor the criteria needed to meet those definitions. Additionally, scientists and medical professionals should apply the same scrutiny and critical thinking to fermented foods as they do to probiotics.

ISAPP encourages healthy debate, critical review of new studies and innovative research. Since ISAPP’s mission is focused on promoting the science of these substances, journalists are invited to reach out as needed to ISAPP for an evidence-based perspective on this evolving field (www.ISAPPscience.org).

ISAPP’s Guiding Principles for the Definitions of ‘Biotics’

/in ISAPP Science Blog /by KC

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

Articulating a definition for a scientific concept is a significant challenge. Inevitably, scientists have different perspectives on what falls inside and outside the bounds of a term. Prof. Glenn Gibson, ISAPP co-founder and longtime board member, recently published a paper that describes his path to coining the word ‘prebiotic’, with this observation: “One thing I have learned about definitions is that if you propose one, then be ready for it to be changed, dismissed or ignored!”

Mary Ellen Sanders with Glenn Gibson

Members of the ISAPP board, however, have remained steadfast in their belief that such definitions are worth creating. They are the basis for shared understanding and coordinated progress across a scientific field.

Developing the consensus definition papers on probiotics, prebiotics, synbiotics, postbiotics and fermented foods was demanding on the part of all involved. The objective of the panels that met to discuss these definitions was clear – to provide common ground for consistent use of this growing body of terms for all stakeholders. Although some disagreement among the broader scientific community exists about some of the definitions, ISAPP’s approach relied on important, underlying principles:

  • Don’t unnecessarily limit future innovation
  • Don’t unnecessarily limit mechanisms of action
  • Don’t unnecessarily limit scope (host, regulatory category, mechanism, site of action, etc.)
  • Require a health benefit on a target host to be demonstrated – otherwise, what is the value of these biotic substances? (Of course, fermented foods were the exception in this criterion, because the value of consuming fermented foods even in the absence of an established health benefit is evident.)
  • Limit to preparations that are administered, not substances produced by in situ activities

In my opinion, many published definitions, including previous ones for postbiotics (see supplementary table here), are untenable because they don’t recognize these principles. There may also be a tendency to rely on historical use of terms, rather than to describe what is justified by current scientific knowledge. A good example of this is provided by the first definition of probiotics, published in 1965. It was “substances secreted by one microorganism that stimulate another microorganism” (Lily and Stillwell, 1965), which is far from the current definition of “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (Hill et al. 2014).

If you’re looking for a concise summary of the five published ISAPP definitions, see here for our definitions infographic.

Additional reflections: I noted with a smile Glenn’s views on ISAPP, specifically on the appropriate pronunciation of the abbreviation ‘ISAPP’. “My only negative is that everyone involved in the organisation aside from 2 or 3 of us pronounce its acronym wrongly.” Most board members, including myself, have always pronounced this as ‘eye-sap’. Glenn opines, “The abbreviation is not eye-SAPP, it is ISAPP (with the ‘I’ – remarkably enough – being spoken as it is in the word ‘International’).” I wonder how he pronounces IBM?

 

 

 

 

ISAPP awards the Glenn Gibson Early Career Research Prize to two diet and gut health researchers

/in ISAPP Science Blog, News /by KC

The ISAPP board of directors is pleased to announce that the 2022 Glenn Gibson Early Career Research Prize has been awarded to two promising researchers in the field of probiotics, prebiotics and related substances.

Dr. Martin Laursen, Senior Researcher at the National Food Institute, Technical University of Denmark, has demonstrated excellence in his work on the impact of probiotics and human milk oligosaccharides on infant gut microbiota and health. Dr. Eirini Dimidi, Lecturer at King’s College in London, UK, has carried out meaningful work on probiotics, prebiotics, and fermented foods and their impact on constipation.

The award criteria stipulated that the researchers must be fewer than five years from their terminal degree, and their scope of research must be basic or clinical research disciplines in the fields of probiotics, prebiotics, synbiotics, postbiotics or fermented foods. In addition, the researchers were required to show evidence of a significant research finding and its publication(s), new ideas that advance the field, and / or evidence of impact through citizenship, general outreach, social media or other means.

The prize committee chose the two recipients from among dozens of applicants and identified each of them as having made important contributions to the field at this early stage in their scientific careers. Each winner will receive a cash prize and an opportunity to speak at the ISAPP annual meeting, to be held in Spain in June, 2022.

Stay tuned to learn more about these rising star researchers!

See here for details about the 2022 Glenn Gibson Early Career Research Prize

Do fermented foods contain probiotics?

/in Consumer Blog, ISAPP Science Blog /by KC

By Prof. Maria Marco, PhD, Department of Food Science & Technology, University of California, Davis

We frequently hear that “fermented foods are rich in beneficial probiotics.” But is this actually true? Do fermented foods contain probiotics?

The quick answer to this question is no – fermented foods are generally not sources of probiotics. Despite the popular assertion to the contrary, very few fermented foods contain microbes that fit the criteria to be called probiotic. But this fact does not mean that fermented foods are bad for you. To uphold the intent of the word probiotic and to explain how fermented foods actually are healthy, we need to find better ways to describe the benefits of fermented foods.

Probiotics are living microorganisms, that when administered in adequate amounts, confer a health benefit on the host (Hill et al 2014 Nat Rev Gastroenterol Hepatol). This current definition reflects minor updates to a definition offered by an expert consultation of scientists in 2001 convened by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization. Evident from the definition, a microbial strain is not a probiotic unless a health benefit has been found with its use. At a minimum, the strain should be proven to be beneficial in at least one randomized controlled trial (RCT). Probiotics must also be defined at the strain level through genome sequencing (a strain is a single genotype of a species).

Fermented foods, on the other hand, have no requirement to improve health. Fermented foods are foods and beverages made through desired microbial growth and enzymatic conversion of food components. This definition was recently formulated by an ISAPP consensus panel of scientific experts to affirm the common properties of all foods of this type and to differentiate foods that may look or taste similar but are not made using microbes (Marco et al 2021 Nat Rev Gastroenterol Hepatol). Fermented foods encompass an expansive variety of foods made from animal and plant sourced ingredients and produced from all types of microbial metabolism. The desired characteristics of these foods are frequently how they look, smell, and taste. There no expectation in this definition that fermented foods alter health in any way.

There is also no requirement for fermented foods contain living microbes at the time they are ingested. Foods such as bread, chocolate, and beer are fermented but then are baked, roasted, and/or filtered. This means those fermented foods cannot be probiotic.

Some fermented foods, such as kimchi and kombucha, are typically eaten with living microbes present. However, the microbes in those foods usually do not meet the criteria to be called probiotic. Whether the fermented food was made at home or purchased from the supermarket, studies investigating whether the microbes in those fermented foods are specifically responsible for a health benefit remain to be done. Those foods also do not contain microbes defined to the strain level, nor is the number of living microbes typically known. An exception to this is if specific strains previously shown to provide a health benefit in one or more RCT are intentionally used in the production of the food and remain viable at expected numbers over the shelf-life of that fermented food product. An example of this would be a commercial fermented yogurt that has an added probiotic strain remaining viable at the time of consumption, beyond the strains that carried out the fermentation.

Despite these distinctions between probiotics an fermented foods, the probiotics term has pervaded common lexicon to mean “beneficial microbes”. In contrast to pathogenic or harmful microbes, beneficial microbes are those that are understood to help rather than hurt bodily functions. However, just as we do not assume that all pathogens cause the same disease or result in the same severity of symptoms, we should also not expect that beneficial microbes all serve the same purpose. By analogy, automobiles are useful vehicles which help us to get from place to place. We do not expect that all automobiles perform like those used for Formula 1 racing. Microbes are needed to make fermented foods and may be beneficial for us, but we should not assume that those drive health benefits like established probiotic strains.

What are the consequences of calling fermented foods probiotic when they include undefined numbers of living microbes for which strain identities are not known? One can suppose that there is no harm in labeling or describing those products as “probiotic” or “containing probiotics”. However, by doing so, confusion and misunderstanding is created and too often, spread by journalists, nutritionists, scientists, and medical professionals. For example, news articles in reputable sources have written that foods like kefir, kimchi, sauerkraut made from beets or cabbage, pickles, cottage cheese, olives, bread and chocolate are rich in probiotics. As misuse perpetuates, what becomes of bona fide probiotics shown with rigorous study to benefit health, such as reducing the incidence and duration of diarrhea or respiratory infections? It becomes difficult to know which strains have scientific proof of benefit. Just as there are laws for standards of food identity, we should strive to do the same when describing microbes in fermented foods.

Avoiding the term probiotic when describing fermented foods should not stop us from espousing the myriad of positive attributes of those foods. Besides their favorable sensory qualities, fermented foods are frequently safer and better tolerated in the digestive tract than the foods they are made from. During the production of fermented foods, microbes remove or reduce toxins in the ingredients and produce bioactive compounds that persist long after the microbes that make them are gone.

Even though the living microbes in fermented foods may not rise to the standard of a probiotic, they may provide health benefits. We just don’t have the studies to prove that they do. With more study, we may find that viable microbes in fermented foods work similarly to probiotics in the digestive tract through shared mechanisms. This is already known for yogurts. Yogurt cultures share the ability to deliver lactase to the intestine, thereby improving tolerance of lactose by intolerant individuals. Clinical and epidemiological studies performed on fermented foods already suggest an association between them and different health benefits but as we recently explained (Marco et al 2021 J Nutrition), more work is needed in order to understand if and what benefits these microbes provide.

For now, we should simply continue enjoying the making and eating of fermented foods and reserve the term probiotics for those specific microbial strains which have been shown to improve our health. Marketers should resist labeling products as containing probiotics if their products do not meet the criteria for a probiotic. Indeed, the descriptor “live and active cultures” more accurately reflects the microbial composition of many fermented foods, and should be used until controlled human trials demonstrating health benefits are conducted.

 

Additional resources:

How are probiotic foods and fermented foods different? ISAPP infographic.

Fermented foods. ISAPP infographic.

What are fermented foods? ISAPP video.

Are fermented foods probiotics? Webinar by Mary Ellen Sanders, PhD.

 

New synbiotic definition lays the groundwork for continued scientific progress

/in ISAPP Science Blog /by KC

By Karen Scott, Mary Ellen Sanders, Kelly Swanson, Glenn Gibson, and Bob Hutkins

When Glenn Gibson and Marcel Roberfroid first introduced the prebiotic concept in 1995, they also conceived that prebiotics could be combined with probiotics to form synbiotics. In 2011, Gibson and Kolida described additional criteria for defining synbiotics and proposed that synbiotics could have either complementary or synergistic activities.

In the past decade, nearly 200 clinical studies on synbiotics have been reported in the literature. Nonetheless, the term itself has been open to interpretation, and the existing definition – a probiotic plus a prebiotic – was inadequate to account for the synbiotic formulations described in the literature or available in the marketplace.

To provide clarity on the definition and lay the groundwork for progress in the years ahead, scientists working on probiotics, prebiotics, and gut health came together in an expert panel. The outcome of this panel, the ISAPP consensus definition and scope of the word synbiotic, has now been published in Nature Reviews Gastroenterology & Hepatology.

A diverse panel of experts

The panel of experts who met to discuss the definition of synbiotics in May, 2019, consisted of eleven interdisciplinary scientists in the fields of microbiology and microbial ecology, gastrointestinal physiology, immunology, food science, nutritional biochemistry, and host metabolism. The panel’s range of experience was important in order to ensure the definition made sense from different scientific perspectives. The panel met under the auspices of ISAPP and was led by Prof. Kelly Swanson.

An inclusive definition

Initially, it seemed logical that synbiotic could be defined as a combination of a probiotic and a prebiotic, with each component needing to meet the criteria for either probiotic or prebiotic according to the previous scientific consensus definitions (Hill, 2014; Gibson, 2017). However, as the group discussed different scenarios and combinations, it became clear that this narrow characterization of a synbiotic could place undue emphasis on the individual components of a synbiotic rather than the combination of these components. For example, the original definition would not include a combination of inulin (a prebiotic) with live microorganisms that did not have probiotic status, even if live microbes in the host selectively utilized inulin and the combination was shown to confer a health benefit.

The definition of synbiotic agreed upon by the panel is: “A mixture, comprising live microorganisms and substrate(s) selectively utilized by host microorganisms, that confers a health benefit on the host.”

The panel discussed exactly which microorganisms must be targeted by the substrate in a synbiotic and decided that the targeted ‘host microorganisms’ can include either autochthonous microbes (those already present in the host) or allochthonous microbes (those that are co-administered).

Further, the panel defined two distinct types of synbiotics: complementary and synergistic. In a ‘synergistic synbiotic’, the substrate is designed to be selectively utilized by the co-administered microorganism(s)—and do not necessarily have to be individual probiotics or prebiotics, as long as the synbiotic itself is health promoting. In a ‘complementary synbiotic’, an established probiotic is combined with an established prebiotic designed to target autochthonous microorganisms— therefore each component of a complementary synbiotic must meet the minimum criteria for a probiotic or a prebiotic.

The definition is purposefully inclusive, so a synbiotic could be established for different hosts, e.g. humans, companion animals, or agricultural animals. Even subsets of these hosts (those of a certain age or living situation) could be targeted by synbiotic products. Moreover, products may be called synbiotics if they target areas of the host’s body outside of the gut (e.g. the skin).

Implications for study design

According to the new definition, different types of studies must be designed for synergistic synbiotics versus complementary synbiotics. For the former, a single study must demonstrate both selective utilization of the substrate and a health benefit. For complementary synbiotics, however, it is only necessary to show a health benefit of the combined ingredients; it is not necessary to show selective utilization of the prebiotic substrate, since selective utilization should have already been established.

The panel remained open to different scientifically valid approaches to demonstrate selective utilization of the substrate. Further, the nature of the ‘health benefit’ was not prescribed, but to the extent biomarkers or symptoms are used, they must be validated.

Continuing scientific progress

The field of synbiotics is evolving – some studies exist to show human health benefits deriving from synbiotic ingredients. While the studies on individual components (probiotics and prebiotics separately) may guide those in the field, there is the possibility that we will find novel uses and applications for synbiotics in the years ahead.

Causality is an important issue that scientists will need to address in this field. The definition of synbiotics rests on an important concept originally advanced in the definition of prebiotics: evidence of health benefit plus selective utilization of the substrate by microbes must be demonstrated. More investigations of causal links between these two things will have to be explored; this is closely connected with ongoing work to uncover probiotic and prebiotic mechanisms of action.

This definition is a first step—and it is fully expected that the field will evolve in the years ahead as more data are generated on the benefits of synbiotics for human and animal hosts.

Find the ISAPP press release on this publication here.

See here for a previous ISAPP blog post on the synbiotic definition.

See below for ISAPP’s new infographic explaining the concept of synbiotics.

Are prebiotics good for dogs and cats? An animal gut health expert explains

/in Consumer Blog, ISAPP Science Blog /by KC

By Kelly S. Swanson, PhD, The Kraft Heinz Company Endowed Professor in Human Nutrition, University of Illinois at Urbana-Champaign, USA

Pet dogs and cats are cherished companions. In developed countries, many households with pets treat them like family members. Similarly to humans, a high level of nutrition and veterinary care promotes health and longevity. As people become more aware of what they feed themselves and their human family, they make the same considerations for their canine and feline companions. Pet food trends have closely followed those of the human food industry over the last couple decades, with high-quality natural and organic foods gaining popularity.

One way pet food companies have enhanced their products is by incorporating functional ingredients into their formulas. Functional ingredients provide benefits beyond that of their nutrient content. One of the most popular target areas for functional ingredients is pet gastrointestinal health, with structure/function claims of “supporting digestive health”, or something similar, being quite common. Loose stools, constipation, and various gastrointestinal disorders and diseases such as inflammatory bowel diseases and irritable bowel syndrome are common in pets. The task of “poop scooping” after the dog in the park or cleaning out the cat’s litterbox provides owners with an opportunity for daily assessment of stool quality and serves as a reminder of how important diet is to gut health.

Benefits of prebiotics for pets

Many ingredients, including dietary fibers, prebiotics, probiotics, synbiotics, postbiotics, and other immunomodulators may provide gastrointestinal benefits to pets, but today we will focus on prebiotics. The most recent ISAPP expert consensus panel on prebiotics clarified that the prebiotic concept not only applies to humans, but also to companion and production animals (Gibson). Dogs and cats evolved as Carnivora, mainly consuming high-protein, high-fat diets that were low in fiber, and their short, simple gastrointestinal tracts have a limited capacity to ferment non-digestible substances. Nonetheless, they possess an active microbiota population, primarily in the colon, that may be manipulated by diet to impact health.

Most prebiotic research in pets has focused on the gastrointestinal tract. Prebiotic administration has been shown to reduce the incidence or severity of infections (Apanavicius; Gouveia), improve stool consistency (Kanakupt), and beneficially shift fecal microbiota and metabolite profiles (Propst). A few have reported the benefits that prebiotics may have on metabolic health, demonstrating improved glucose metabolism and insulin sensitivity in pets consuming prebiotics (Respondek; Verbrugghe). Since we’re looking at foods rather than at medicines that address disease, the majority of research has been conducted in healthy animals so evidence of health improvements in diseased pets is sparse.

Types of pet-friendly prebiotics

Although a few studies have tested galactooligosaccharides (GOS), mannanoligosaccharides, and other potential prebiotics, by far the most common prebiotics studied and present in pet foods are the non-digestible fructans. Natural sources, such as chicory, or isolates and extracts that have a high purity, including short-chain fructooligosaccharides (FOS), oligofructose, and inulin, are all present in pet foods.

Which pets benefit most?

Similar to dietary fiber, the need for prebiotic inclusion is dependent upon diet type and formulation. Animals consuming plant-based diets that are rich in natural fibers and non-digestible oligosaccharides likely do not require additional fermentable substrate in the formula. Dogs and cats fed high-protein, meat-based diets, however, typically have greater fecal odor, a higher colonic pH, and higher density of potential pathogens due to a high rate of protein fermentation. In those diets, prebiotic inclusion may help animals normalize their gut microbiota abundance and metabolism.

Prebiotics may be fed to all pets, but will likely provide the greatest benefits to geriatrics, animals who are or have received antibiotics, those under high stress conditions, or those with certain gastrointestinal disorders. The low caloric density of prebiotics and the metabolic benefits that come from their fermentation will be most beneficial to pets with obesity and diabetes. As for all functional ingredients, dosage is important. When comparing dogs and cats, dogs usually can tolerate a higher dosage than cats. In regard to dog size, small dogs can typically tolerate a higher dosage (per unit body weight) than large dogs, which are more susceptible to loose stools. In most commercial pet foods, prebiotic inclusion levels are <0.5% of the formula to limit side effects.

Further research on prebiotic substances

Using the powerful tools that are now available to study gut microbiota and host physiology, future research can hopefully determine what microbes are most important to the health of dogs and cats and identify mechanisms by which prebiotics provide health benefits to pets. Further testing, which may include plant-based ingredients, yeast-based products, and milk oligosaccharide mimics, will hopefully identify other prebiotic substances and continue to expand our knowledge in the field.

 

Kelly Swanson joined the ISAPP board of directors in June, 2020, providing valuable expertise in animal gut health and overall health. Swanson also chaired the 2019 ISAPP-led international consensus panel on the definition of synbiotics.

 

 

 

Growing interest in beneficial microbes and fermented foods in Argentina

/in Consumer Blog, ISAPP Science Blog /by KC

By Prof. Gabriel Vinderola PhD, Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina

Awareness of gut microbes, fermented foods and probiotics has been on the rise in Argentina. Nutritionists and influencers, who in recent years have begun promoting a healthier lifestyle, are leveraging their social networks to post how-to instructions for making fermented foods, advice to promote a ‘healthier’ microbiota, and information on the potential role of probiotics and prebiotics in human health. But are these news items and recommendations based on science? Not always! I’ve been fortunate to have had the opportunity to make sure the science is correctly communicated to a broad audience on the microbiome, fermented foods, probiotics and prebiotics.

In Argentina, for the last 50 years, there has been on the air a TV show with a particular format: the hostess, Miss Mirtha Legrand, invites 4-6 people to have lunch every Sunday, talking about politics, economy, popular culture, arts and even science for 3 hours. According to her, this is the longest continuously running TV program in the world. Every Sunday several thousands of people from Argentina, Uruguay and Paraguay tune in. In October 2019, I was invited to join the table and to comment about the invisible world inside and around us. We discussed how we can profit from bacteria through fermented foods and probiotics, and how to feed our gut microbes with prebiotics. In fact, in 2019, I gave more than 40 talks on this topic to scientific audiences at conferences, as courses for Ph.D. students, as seminars and as workshops. These efforts are targeted not only to local scientists and students, but also to children in schools, local sport clubs in small towns, gyms and hospitals. The interest in friendly bugs is wide-ranging and varied, and fueled by information from radio and TV programs.

“Having lunch with Mirtha Legrand”, a talk show on television for more than 50 years in Argentina, where the discussion on beneficial microbes was brought to the table by Prof. Gabriel Vinderola (far right). Mirtha Legrand, now 93 years old, is in the center (October 3rd, 2019).

The enthusiasm of the audience was immediately evident. Lots of messages came by email, WhatsApp, Facebook or Instagram. People were anxious to know more, inquiring about trustworthy sources to read scientific-based but “easy-to-understand” material, posing specific questions about their gut feelings, where to get these probiotics and prebiotics or how to make fermented foods in a safe manner. Fortunately, the ISAPP infographics on probiotics and prebiotics were already available in Spanish, translated by Miguel Gueimonde (Spain) and me, and these were a welcome resource. Yet people still wanted more information, and asked more and more specific questions.

Spurred by such widespread interest, I contacted a local lawyer-turned-chef, Ana Milena Giacomini, who left behind her professional law career to open a small restaurant with a menu heavily based on fermented foods. She features such delights as home-made yoghurt, chucrut, kimchi, sugary kefir, fermented hummus, sourdough bread, pancakes made out of fermented rice flour, kombucha, kvass and a gasified drink from fermented ginger. With her, we organized 4-hour workshops, which are currently on hold due to COVID-19. These workshops feature Ana preparing some of these fermented foods live, followed by tasting, while I explain the science and microbiology behind them. I share factors related to the identity, safety, stability, and potential health effects of these products. I emphasize the differences between fermented foods and probiotics, while discussing the potential value of incorporating fermented foods, probiotics and prebiotics to the daily diet as a way to promote gut health. I provide more specific information on health effects for which robust meta-analyses are available to support the microbes’ use, such as prevention of antibiotic-associated diarrhea in children, treatment of infant colic, prevention of allergies, and downregulation of intestinal inflammation. Other workshops with different chefs from different locations in Argentina are in line for when the coronavirus pandemic ends.

Part of the four-course dinner containing fermented foods prepared by chef Martin Russo. The starter consisted of fermented carrots and hummus, served on sourdough bread (pictured).

These workshops are expected to be attended by 30-35 people each time. Nutritionists are interested in giving sound responses to their clients, who hear about these topics in the media or in social networks. But also, people come who want to learn how to make fermented foods, where to find probiotics and prebiotics, or to gain clear guidance on how to incorporate live bacteria to their diets. Other health professionals (gastroenterologists, pediatricians), educators and even people from the industry also attend.

 

The dessert was ice cream balls covered by the mother of vinegar (transparent circle on the top), rinsed and sweetened.

Most people interested in attending these workshops have narrow experience with fermented foods, only being familiar with such things as yoghurt, cheese, wine or beer. Some of them do not know that these foods are indeed fermented, or do not have a clear idea what fermentation is about. Most of them also have a very limited awareness, or even misinformation, about probiotics and prebiotics. These workshops offer the possibility for the curious to learn and to taste new foods, to get insights on the science behind fermented foods, probiotics and prebiotics, and to learn the differences between them in a science-based manner in an “easy-to-follow language”. These encounters are a great way to expand the interest by the general public on the invisible world inside and around us.

Is probiotic colonization essential?

/in Consumer Blog, ISAPP Science Blog /by KC

By Prof. Maria Marco, PhD, Department of Food Science & Technology, University of California, Davis

It is increasingly appreciated by consumers, physicians, and researchers alike that the human digestive tract is colonized by trillions of bacteria and many of those bacterial colonists have important roles in promoting human health. Because of this association between the gut microbiota and health, it seems appropriate to suggest that probiotics consumed in foods, beverages, or dietary supplements should also colonize the human digestive tract. But do probiotics really colonize? What is meant by the term “colonization” in the first place? If probiotics don’t colonize, does that mean that they are ineffective? In that case, should we be searching for new probiotic strains that have colonization potential?

My answer to the first question is no – probiotics generally do not colonize the digestive tract or other sites on the human body. Before leaping to conclusions on what this means for probiotic efficacy, “colonization” as defined here means the permanent, or at least long-term (weeks, months, or years) establishment at a specific body site. Colonization can also result in engraftment with consequential changes to the gut microbiota composition and function. For colonization to occur, the probiotic should multiply and form a stably replicating population. This outcome is distinct from a more transient, short-term (a few days to a week or so) persistence of a probiotic. For transient probiotics, it has been shown in numerous ways that they are metabolically active in the intestine and might even grow and divide. However, they are not expected to replicate to high numbers or displace members of the native gut microbiota.

Although some studies have shown that digestive tracts of infants can be colonized by probiotics (weeks to months), the intestinal persistence times of probiotic strains in children and adults is generally much shorter, lasting only few days. This difference is likely due to the resident gut microbiota that develops during infancy and tends to remain relatively stable throughout adulthood. Even with perturbations caused by antibiotics or foodborne illness, the gut microbiome tends to be resilient to the long-term establishment of exogenous bacterial strains. In instances where probiotic colonization or long-term persistence was found, colonization potential has been attributed more permissive gut microbiomes specific to certain individuals. In either case, for colonization to occur, any introduced probiotic has to overcome the significant ecological constraints inherent to existing, stable ecosystems.

Photo by http://benvandenbroecke.be/ Copyright, ISAPP 2019.

This leads to the next question: Can probiotics confer health benefits even if they do not colonize? My answer is definitely yes! Human studies on probiotics with positive outcomes have not relied on intestinal colonization by those microbes to cause an effect. Instead of colonizing, probiotics can alter the digestive tract in other ways such as by producing metabolites that modulate the activity of the gut microbiota or stimulate the intestinal epithelium directly. These effects could happen even on short-time scales, ranging from minutes to hours.

Should we be searching for new probiotic strains that have greater colonization potential? By extension of what we know about the resident human gut microbiota, it is increasingly attractive to identify bacteria that colonize the human digestive tract in the same way. In some situations, colonization might be preferred or even essential to impacting health, such as by engrafting a microbe that performs critical metabolic functions in the gut (e.g. break down complex carbohydrates). However, colonization also comes with risks of unintended consequences and the loss of ability to control the dose, frequency, and duration of exposure to that particular microbe.

Just as most pharmaceutical drugs have a transient impact on the human body, why should we expect more from probiotics? Many medications need to be taken life-long in order manage chronic conditions. Single or even repeated doses of any medication are similarly not expected to cure disease. Therefore, we should not assume a priori that any observed variations in probiotic efficacy are due to a lack of colonization. To the contrary, the consumption of probiotics could be sufficient for a ripple effect in the intestine, subtly altering the responses of the gut microbiome and intestinal epithelium in ways that are amplified throughout the body. Instead of aiming for engraftment directly or hand-wringing due to a lack of colonization, understanding the precise molecular interactions and cause/effect consequences of probiotic introduction will lead to a path that ultimately determines whether colonization is needed or just a distraction.

Thank You to ISAPP’s 2019 Industry Advisory Committee Members

/in featured, News /by ISAPP

by Dr. Mary Ellen Sanders

This year, a record 50 companies that are dedicated to a science-based approach to the probiotic and prebiotic industries joined ISAPP. As members of the Industry Advisory Committee (IAC), these companies provide critical insights to ISAPP’s all-academic board of directors as they leverage ISAPP to address challenges facing these and related industries.

ISAPP will welcome representatives from each IAC company at the ISAPP Annual Meeting – taking place next week May 14th-16th in Antwerp, Belgium.

Industry dues provide support for ISAPP activities, which would not be possibly without funding by our IAC members. Summaries of ISAPP activities are found here.

Thank you IAC!

ISAPP Tests the Water with a New Session Format at Annual Meeting: The Springboard

/in featured, News /by ISAPP

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

Along with more traditional lectures, the distinctive five-minute rapid-fire late breaking news session and the small, topical discussion groups have been staples of the annual ISAPP meetings. This year in Antwerp, ISAPP is trying yet another innovative approach – a session we are calling “The Springboard.” The witty Prof. Glenn Gibson will chair, sure to make the session entertaining as well as inspiring.

The Springboard is a session designed to integrate audience and facilitators’ viewpoints in an interactive format. The topic:  What can scientists and industry do to spring probiotics and prebiotics into mainstream health management? Four facilitators, each focused on a different perspective (industry, politics, medical/clinical or science/research), will present their visions. The audience, which will be divided into 10 subgroups, is challenged with the task of generating innovative ways to achieve the visions.

ISAPP plans to write up the most interesting solutions for publication. Watch for the output from this new session after the 2019 ISAPP annual meeting – May 14-16.

The Art of Interpretation

/in featured, News /by ISAPP

By Prof. Gregor Reid, BSc Hons PhD MBA ARM CCM Dr HS, Lawson Research Institute, University of Western Ontario, Canada

It takes a certain degree of intelligence to become a scientist, and certainly hard work to be able to fund a lab and students. Yet, is it not bemusing when scientists cannot interpret simple things like definitions and the results of human studies?

I’ve written repeatedly, as have others, about the definition of probiotics (in case you forgot – “Live microorganisms that, (or which) when administered in adequate amounts, confer a health benefit on the host”),1,2 and yet people look at it and must think that ‘dead’ fits, as does ‘consume’, as does ‘colonize’. It beggar’s belief how such a simple definition can be so badly interpreted by intelligent people.

Time after time papers I review mis-write and/or misinterpret the definition. Conference after conference, I hear dieticians, pharmacists, physicians, scientists not only get the definition wrong, but say things like ‘the probiotics in kombucha’ when there are none, ‘we have lots of probiotics in our gut’ when you don’t unless you consumed them, ‘the lactobacilli need to colonize’ when this was never a prerequisite nor does it happen except in rare instances.

The interpretation gets more difficult when people use terms that are completely undefined like ‘psycho-biotics’ and ‘post-biotics’. Even ‘dead probiotics’ have been used in clinical trials – God help us when the authors can’t even define it. Why stop at killing probiotic strains? Why not just kill any bacterial strain? Even the gut-brain axis which is now mentioned everywhere in the literature is undefined and unproven. The vagus nerve links to many body sites as does the nervous system, making it exceedingly difficult to prove that brain responses are only due to the gut microbes.

Everyone can site a manuscript that has been badly analyzed, interpreted or peer-reviewed, or whose findings are overblown. But let’s not excuse this as ‘it’s just science’ or ‘it’s just the way it is.’ No, it is not. When a paper uses a product that is stated to be ‘probiotic’, there is an onus on the authors to make sure the product meets the appropriate criteria. These have been stated over and over again and reiterated this March, 2019.3

If scientists and science writers are really that smart, then how do they keep getting this wrong? How do we let a poorly analyzed paper get published and allow authors to say that Bacteroides fragilis is a probiotic that can treat autism?4,5 And when this leads to companies claiming probiotics can treat autism, why do other scientists convey cynicism for the field instead of against their colleagues and specific companies making the false claims?

Where does opinion cross the line with ignorance or stupidity? Martin Luther King Jr. must have predicted life today when he said, “Nothing in all the world is more dangerous than sincere ignorance and conscientious stupidity.”

Is it envy or anger that drives the anti-probiotic sentiments? It seems to go far beyond a difference of opinion. When the BBC and JAMA fail to comment on two much better and larger studies on the effects of probiotics published6,7 at the same time as the ones in Cell8,9 that were promoted by press releases, what is driving opinion? The science or the press releases? Are the journalists and communications’ people interpreting study results vigorously? One cannot believe they are.

In an era where anyone can write anything at any time and pass it along to the world, what are we recipients to do? Just go with our instincts? Soon, we will not know the difference between fact and fake news. The avatars will be so real, we will act on falsehoods without knowing. When all news is fake, where does that leave us as people, never mind scientists?

Manuscripts are sent for peer-review but how many reviewers are experts in bioinformatics, molecular genetics, clinical medicine, biostatistics and what happens on the front line of products to consumers or patients? Like it or not, poor studies will get out there and it will be the media who will tell the story and interpret the findings or press releases.

One must hope that confirmatory science will continue and if it fails, the writers and readers will stop citing the original incorrect report. But how often does that happen? And what are we left with?

It takes effort to object or fight back, but if we don’t then the fake news will become the norm.

Try interpreting that if you will.

 

Literature Cited

  1.  FAO/WHO. 2001. Probiotics in food.  http://www.fao.org/food/food-safety-quality/a-z-index/probiotics/en/
  2. Hill C. et al. 2014. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotics. Nat. Reviews Gastroenterol. Hepatol. 11(8):506-14.
  3. Reid G. et al. 2019. Probiotics: reiterating what they are and what they are not. Front. Microbiol. 10: article 424.
  4. Hsiao et al. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 155(7):1451-63.
  5. Sharon G, et al. 2016. The central nervous system and the gut microbiome. Cell. 167(4):915-932.
  6. Korpela K. et al. 2018. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants. Microbiome. 6(1):182.
  7. De Wolfe, T.J. et al. 2018. Oral probiotic combination of Lactobacillus and Bifidobacterium alters the gastrointestinal microbiota during antibiotic treatment for Clostridium difficile infection. PLoS One. 13(9):e0204253.
  8. Suez J. et al. (2018). Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018 Sep 6;174(6):1406-1423.e16.
  9. Zmora N. et al. 2018. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. Sep 6;174(6):1388-1405.e21.

University confers Distinguished University Professor status on ISAPP board of directors member Gregor Reid

/in featured, News /by Mary Ellen Sanders

ISAPP board of directors member Dr. Gregor Reid has received a Distinguished University Professorship (DUP) award from his institution, University of Western Ontario in Canada, in honour of his exceptional scholarly career achievements. Reid, a Professor of Microbiology & Immunology, and Surgery, was aptly described as ‘a Canadian and international pioneer’ in research related to probiotics and the microbiome. A special area of research focus is how these relate to women’s health.

The many letters after Reid’s name reflect his extensive qualifications: BSc Hons, PhD, MBA, ARM CCM, Dr HS, FCAHS, FRS; he also has over 500 scientific publications to his name. But more than that, the impact of Reid’s work is seen all over the world. He has researched novel probiotic therapies that are now being used in different countries and settings, and his innovations have resulted in numerous probiotic-related patents. Reid also makes a point of empowering those in need: in Uganda, Kenya, and Tanzania, for example, he participated in a project to establish probiotic yogurt kitchens that allowed local women to further build sustainable yogurt businesses.

Reid’s connection with ISAPP goes back a long way—he hosted the first ever ISAPP meeting in London, Canada in May of 2002, and served as ISAPP’s second president. Still a dedicated member of the ISAPP board of directors, he is respected for his innovative ideas to move ISAPP forward and his incredible efficiency. As his colleagues know, no one gets more done more quickly than Gregor!

Today he is known as a steward of the proper use of the term ‘probiotic,’ a fitting description since he chaired the FAO/WHO expert consensus that published the now globally-recognized definition of the word probiotic back in 2001.

The ISAPP colleagues of Dr. Gregor Reid extend a warm congratulations on his Distinguished University Professorship award; they applaud his remarkable scientific accomplishments, his energy, and his determination to help the field advance.

See here for the full news article about the award.

Probiotics: Money Well-Spent For Some Indications

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

Eamonn M M Quigley MD, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA; Hania Szajewska MD, The Medical Univesrity of Warsaw, Department of Paediatrics, Poland; Dan Merenstein MD, Department of Family Medicine, Georgetown University

We read with interest and some concern the Medical News and Perspectives article by Jennifer Abbasi titled “Are Probiotics Money Down the Toilet? Or Worse?” (Abbasi 2019).  As researchers committed to the study of fecal microbiota transplant, prebiotics and probiotics, we find the title overly sensationalist for an article that ultimately provides a more nuanced view. It is unfortunate that the author focused on studies which either did not report on any clinical outcome and hence provide limited insight on the effectiveness of probiotics, or, whose null results likely reflect the late timing of the intervention while failing to refer to many high-quality studies that illustrate the subtlety of commensal and probiotic bacterial actions or clinical efficacy. Tanoue and colleagues provide a reminder that commensal engagement with the immune system is selective and precise (Tanoue et al. 2019). As Dr Knight points out, it would be surprising to witness the same response to any intervention in all individuals (Abbasi 2019). Efforts to individualize medical interventions, including probiotics, are worthwhile, but not yet realized. Until then, available evidence must be critically considered, but not ignored.  We wholeheartedly agree with the call for high quality clinical studies of probiotics but assert that it is also important to stress the challenges of performing clinical studies that seek to demonstrate clinical benefits in healthy human subjects; they require large study populations and are consequently very expensive. That clinical studies have been performed and demonstrated robust and clinically meaningful outcomes was illustrated by the study of Panigrahi where they demonstrated that an intervention comprising a probiotic plus prebiotic reduced sepsis among high-risk infants in rural India (Panigrahi et al. 2017). In the meantime, meta-analyses of smaller studies can provide insights into clinical benefit or harm. For example, systematic reviews and meta-analyses have consistently supported a role for probiotics in the prevention of Clostridium difficile–related illness, leading a JAMA review to state: “moderate-quality evidence suggests that probiotics are associated with a lower risk of C. difficile infection” (Goldenberg et al. 2018). Balanced with the low number needed to harm, probiotic interventions are attractive clinical options. We also question Abbasi’s focus on colonization as there is little, if any, evidence that this is necessary for probiotic activity.

We stress the obligation to provide a balanced view of the field which provides equal emphasis on successes as well as failures. No two probiotics (or probiotic cocktails) are alike; we should not expect they all have the same clinical impact.

 

References

  1. Abbasi J. Are probiotics money down the toilet? Or worse. JAMA 321(7):633-635. doi:10.1001/jama.2018.20798
  2. Tanoue T, Morita S, Plichta DR, et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019;565:600-605.
  3. Panigrahi P, Parida S, Nanda NC, et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017;548:407-412.
  4. Goldenberg JZ, Mertz D, Johnston BC. Probiotics to prevent Clostridium difficile infection in patients receiving antibiotics. JAMA 2018;320:499-450. 

 

Acknowledgements:

Conflicts of interest:

All three authors are members of the Board of Directors of ISAPP

Eamonn M M Quigley holds equity in Alimentary Health and has served as a consultant to Alimentary Health, Allergan, Axon Pharma, Biocodex, Glycyx, Menarini, Pharmasierra, Salix and Vibrant.

Hania Szajewska reports no conflicts

Dan Merenstein has served as a consultant to Bayer, Debevoise & Plimpton, Pharmavite and Reckitt Benckiser

New ISAPP video gives an overview of fermented foods and their health benefits

/in featured, News /by Mary Ellen Sanders

Fermented foods are not the same as probiotic-containing foods. So what’s the difference? Do both of them confer the same health benefits?

These topics are addressed in ISAPP’s latest video, which takes viewers through the scientific basics of fermented foods (see here). Yogurt, kimchi, and cheese fall into this category of foods, which are transformed by growth and metabolic activity of microbes.

Some fermented foods contain live microbes that travel through the digestive tract, interact with cells, and support the intestinal microbiota. Their potential health benefits are of interest, too: not only do fermented foods improve digestibility, but initial studies show they also improve the immune system and prevent acute illnesses.

The upshot? Naturally fermented foods are worth incorporating in your daily diet.

This educational video was commissioned by the ISAPP board of directors with input from several additional scientific experts.

Limitations of microbiome measurement: Prof. Gloor shares insights with ISAPP

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

February 20, 2019

The number of papers published on the human microbiome is growing exponentially – but not all of the studies are equally well designed or reported. Evaluating the latest research requires a basic understanding of the latest approaches to microbiome methods and data analysis.

To help equip scientists not conducting microbiome research with the tools to understand microbiome-focused publications, ISAPP hosted a webinar titled Understanding microbiome experiments: a critical assessment of methods and data analysis. The webinar featured Gregory Gloor, PhD., Professor, Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, Canada.

Prof. Gloor’s slides are available here.

Prof. Gloor opened his talk with a sobering perspective: the current body of microbiome publications is fraught with problems. There is a fundamental lack of reproducibility in the microbiome field (Sinha et al. 2017). This is largely due to the large number of tools available and a lack of an a priori established research plan for microbiome analysis, which should be consistently followed throughout a project. At every step of the way, many decisions must be made regarding wet lab methods, bioinformatics toolsets and statistics to use. Different choices lead to different results. Once the biological specimens are assayed, choices for bioinformatics and statistical analyses can greatly influence the conclusions. In short, it’s possible to view the data through so many different lenses that eventually a researcher can find a story worth telling. How close that story comes to the truth is a principle that sometimes is sacrificed for the sake of an interesting story.

Another important challenge to the field is representative sampling. Too few samples are typically taken, often because of cost limitations, so that the samples do not reasonably approximate the truth about the environment being sampled. Conclusions from such studies result in both many false positives and many false negatives.

Prof. Gloor also warned about outsourcing microbiome analysis. Commercial entities often use every metric, hoping the customer will get some outcome they hoped for. Further, their tools are often outdated or proprietary. So caution must be used – there is no substitute for expertise.

Some suggestions for improving outcomes were offered:

  • Each project should stipulate a research approach and outcome a priori, which is consistently followed throughout the project.
  • Methodological consistency is important within a lab, but analytical methods do not necessarily need to be standardized across all labs. If all labs use the same methods, consistent, but incorrect, outcomes may result. So use of different metrics is good, but methods should be consistent within a project. The value of different research groups using different methods to ask particular research questions is that if the same result emerges from different approaches, it increases confidence that the results are true.
  • Gloor cautioned that microbiome datasets are compositional, and compositional data approaches must be used (Gloor et al 2017).
  • Functional readouts have less methodological variation than taxonomic readouts. Therefore, functional analysis of shotgun metagenomics or shotgun metatranscriptomics is typically a more reproducible, and also more informative, readout.
  • Recent advances have significantly decreased the cost of performing shotgun metagenomics for both taxonomic and functional readouts (Hillmann et al 2018).
  • There are now near-complete microbial genomic datasets available for European, North American and Asian populations (Almeida et al 2019) that will make it easier to functionally map datasets.

Prof. Gloor mentioned an interesting aside: prior clinical trial registration, ~60% of large clinical trials showed benefit of the intervention being tested. After the registration process required declaration of primary research outcomes, that number dropped to closer to 10% (Kaplan and Irvin 2015). This suggests that primary outcomes and analysis methods need to be in place to restrict researcher bias. Right now such mechanisms are insufficient in the microbiome field.

Prof. Gloor’s paper, Microbiome Datasets Are Compositional: And This Is Not Optional, provides great background reading for this webinar.

This webinar was developed by ISAPP Industry Advisory Committee representatives as an extension of the annual IAC Learning Forum.

Dr. Gloor is a professor of biochemistry with broad experience in molecular biology, genetics and genomics. His research is focused on the development of tools to examine 16S rRNA gene composition, gene expression of mixed population samples and metabolomic analysis of clinical samples. He is currently working on developing and adapting principled methods to characterize correlation and differential abundance in sparse, high throughput sequencing data as generated in 16S rRNA gene sequencing surveys, meta-genomics and meta-transcriptomics. One of his primary contributions has been the ALDEx2 tool in Bioconductor for the analysis of high-throughput experiments that generate counts per sequence tag: 16S rRNA gene sequencing, metagenomics, transcriptomics and selex-type experiments.

ISAPP’s prebiotics & probiotics infographic now available in Russian

/in featured, News /by Mary Ellen Sanders

‘International’ is the first word in ISAPP’s title—and the organization takes seriously its commitment to advancing education about probiotics and prebiotics in countries around the world. ISAPP members are happy to announce that the infographic “Effects of Prebiotics and Probiotics on our Microbiota” is now available in Russian. See here.

In an effort to reach broader global populations with its science-based communications on probiotics, prebiotics and fermented foods, ISAPP is undertaking steps to translate its infographics into multiple languages. Expected in the next month are translations of ISAPP’s popular “Probiotics” and “Prebiotics” infographics, which will be available in Bulgarian, Chinese, Dutch, French, Indonesian, Italian, Polish, Portuguese, Russian, and Spanish. (See here for all available translations of ISAPP infographics.)

The translation efforts, led by Dr. Roberta Grimaldi from University of Reading (UK), are made possible by many translators who are contributing generously of their time and skills.

Humpty Dumpty and the Microbiome

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

Prof. Colin Hill, Microbiology Department and Alimentary Pharmabiotic Centre, University College Cork, Ireland (@colinhillucc)

“When I use a word,” Humpty Dumpty said, in rather a scornful tone, “it means just what I choose it to mean—neither more nor less.”

Microbiome science is an evolving discipline, and new terminology is an important part of any developing field.  But precise language is important, especially in a multidisciplinary field with researchers from many diverse scientific backgrounds.  Language provides us a means of communicating with brevity and accuracy, but this is effective only if the reader is deriving the correct (intended) information from the author.

For example, is there a difference between ‘microbiome’, ‘microbiota’ and ‘microflora’?  Are the terms interchangeable, or would it be useful to have them mean related but distinctly different concepts?  I have heard people state that ‘microbiota’ refers to the microbial content of an environment, whereas ‘microbiome’ refers to the microbes AND their environment (the biome).  I have heard others suggest that ‘microbiome’ actually refers to the genetic content of a particular microbiota, in the same way that the genome is the genetic content of an organism.  Some definitions assert that the microbiome/microbiota/microflora only describes the microbial cells (bacteria, archaea and fungi) in a particular niche, while others include non-cellular microbes such as viruses and bacteriophage in their definition.  It has also been pointed out that ‘microflora’ is a misnomer, since technically the term ‘flora’ is reserved for the kingdom Plantae.

A few other examples.  Do we all know what is meant when someone uses the term ‘metagenomics’?  Also, people often refer to analysing the microbiome by 16S – but they are really only analysing the bacterial fraction of the microbiome, the ‘bacteriome’.  Of course ‘16S’ itself is not a valid term – it is 16S rRNA genes that are being analysed.  Would a clear distinction between microbiome, bacteriome, phageome, mycome, virome, archaeome and all the other ‘omes’ help or hinder our understanding of the subject under discussion?  Should most studies actually use the term ‘faecal bacteriome’ rather than ‘gut microbiome’, since it is almost always faeces that is under investigation, and usually only the bacterial component?

I am not going to call out any individuals for abuse of language, since I am pretty sure I could look at my own output and find lots of examples of poorly expressed concepts.  But does any of this matter or am I simply being pedantic? I think it does matter, since if terms are poorly defined it may lead to confusion on the part of the reader (or listener), whereas the authors (or speakers) may know exactly what they mean – neither more or less, as suggested by Humpty Dumpty.

ISAPP has convened consensus panels on the meaning of some very commonly used terms such as probiotic1 and prebiotic2, but there is a limit to this activity, and consensus panels cannot be convened for every new term.  Even with these consensus papers, we still have a plethora of additional terms surrounding beneficial microbes, including paraprobiotics (killed microbes), psychobiotics (originally defined as probiotics with a mental health benefit, but the definition has recently been expanded to any exogenous influence whose effect on the brain is bacterially-mediated3), synbiotics (probiotics and prebiotics administered simultaneously – a term for which ISAPP is convening another Consensus Panel in 2019), live biotherapeutics, etc, etc.  One site I saw referred to bacteriophage as a prebiotic, using the argument that they can influence a microbiome in a selective manner to achieve a beneficial outcome.  This is surely a good example of where the ISAPP definition could provide clarity since prebiotics have to be utilised in order to qualify for the term. Other terms we often use without an agreed consensus as to their meaning are ‘dysbiotic’ (when we could use disturbed, or different, or disrupted), ‘unculturable’ (when we usually mean ‘not yet cultured as far as I know but I haven’t really tried’), ‘hypothetical genes’ (when we actually mean ‘function unknown’), ‘stability’, ‘resilience’, etc.  It may be useful to have some kind of standardised microbiome dictionary, or an accepted glossary of terms.  This is not a new idea (so few of mine ever are), and Julian Marchesi and Jacques Ravel published a lovely short paper to this effect in 20154.  The World Microbiome Day website also has a very short Glossary5.

Obviously, words must be the servants of the author and should not restrict expression or limit our ideas, and in many instances context can make it abundantly clear what meaning is intended by the author.  But in general, a strict definition is not the enemy of understanding, but makes it easier for author and reader to share common ground.

Who should create and curate such a Microbiome Glossary?  Ideally it would be interactive, perhaps along the line of a wiki page, where people could provide their newly coined terms along with a strict definition and arrive at a consensus for commonly used terms.  Reviewers of journal papers and reviews could help, by challenging authors on what terms they use, and whether or not they are the appropriate ones.

Meanwhile, I have to go back to the lab to do some comprehensive metagenomics on the gut microbiome – by which I mean that a competent scientist who works with me is going to go into the lab and conduct a particular form of 16s rRNA gene analysis to profile the more abundant members of the bacteriome of a portion of a faecal sample which has been collected, stored and extracted according to our in-house protocols.  Obviously!

 

  1. Hill et al., 2014. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the scope and appropriate use of the term probiotic.  Nat. Rev. Gastroenterol. Hepatol. 11, 506.
  2. Gibson et al., 2017. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.  Nat. Rev. Gastroenterol. Hepatol. 14, 491.
  3. Sarkar et al., 2016. Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals.  Trends in Neurosciences 39, 763
  4. Marchesi JR and J. Ravel. 2015. The vocabulary of microbiome research: a proposal.  Microbiome 3, 31
  5. http://worldmicrobiomeday.com/glossary-of-microbiome-terms/

Importance of understanding probiotic mechanisms of action

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

By Prof. Sarah Lebeer, Universiteit Antwerpen, Belgium

At present, we do not fully understand the mechanistic basis of many well established probiotic health benefits. This limits our ability to predict which probiotics are likely to be effective.

For instance, prevention of antibiotic-associated diarrhea and necrotizing enterocolitis are health benefits that are well substantiated by meta-analyses, which combine results on many probiotic strains. But what the effective strains have in common from a mechanistic perspective is not known. We cannot yet pinpoint one or a few molecules produced by these strains that might drive the clinical effects. This is likely due to interplay between both host and probiotic factors. These health conditions are complex pathologies and the probiotic strains are living micro-organisms likely working through multiple mechanisms and molecules.

This is in contrast to some more clearly defined situations. Lactose maldigestion results from a deficiency in the enzyme lactase, which is required for converting lactose to glucose and galactose in the small intestine. If lactose is not broken down, it reaches the colon and is fermented by the gut microbiota, leading to symptoms. Some probiotic bacteria (including those present in yoghurt) contain lactase, which can reduce the typical symptoms of lactose digestion.

Several colleagues and I published a recent paper (Kleerebezem et al. 2019) discussing the importance of understanding mechanisms of action. We argue that such knowledge will enable: “(i) selection of more effective probiotic strains; (ii) optimization of probiotic product manufacturing and quality assurance, (iii) improved design of probiotic formulation, and (iv) support of the design of effective clinical trials with the best chance of realizing benefits to human health.”

While knowledge of the mechanism of action is not necessary for translation to effective products, it provides important insights that can improve actions throughout the translational pipeline.

The strain-specificity of different mechanisms of action is another point that will be clarified by future mechanism-focused research. Different probiotic strains clearly express different mechanisms, but some mechanisms are also shared (Sanders et al. 2018). How different host- and probiotic-specific factors interact to achieve a clinically successful intervention remains to be unraveled.

kelly_swanson

ISAPP plans consensus panel on synbiotics

/in featured, News /by Mary Ellen Sanders

The term ‘synbiotic’ – which refers to a substance that combines both a probiotic and prebiotic – lacks a concise, modern definition. Stakeholders, including researchers, regulatory experts, consumers, marketers, industry scientists and healthcare providers, would benefit from a clear definition of synbiotics, a concise review of the state of the science of synbiotics, and a clarification of what kinds of products fall under the synbiotic scope.

ISAPP will convene a panel of top scientific experts on May 13th in Antwerp to develop a consensus around this topic. This panel will be chaired by Prof. Kelly Swanson, The Kraft Heinz Company Endowed Professor in Human Nutrition, Professor in the Department of Animal Sciences and Division of Nutritional Sciences, and Adjunct Professor in the Department of Veterinary Clinical Medicine at the University of Illinois at Urbana-Champaign. Prof. Swanson is known for his research on the mechanisms by which nutritional interventions affect health outcomes in both animals and humans. He is a co-author of the 2017 ISAPP consensus statement on the definition and scope of prebiotics.

As with the ISAPP consensus statements on probiotics (Hill et al. 2014) and prebiotics (Gibson et al. 2017), ISAPP is working with Nature Reviews Gastroenterology and Hepatology to publish the outcome of the synbiotics panel.

ISAPP’s focus on the science of probiotics and prebiotics makes it uniquely positioned to champion a panel of experts to discuss the definition and scientific justification for synbiotics.

The consensus panel members are:

  • Kelly Swanson, University of Illinois at Urbana-Champaign, USA (chair)
  • Glenn Gibson, University of Reading, UK
  • Gregor Reid, University of Western Ontario, Canada
  • Kristin Verbeke, University of Leuven (KU Leuven), Belgium
  • Nathalie Delzenne, Université Catholique de Louvain, Belgium
  • Robert Hutkins, University of Nebraska-Lincoln, USA
  • Karen Scott, University of Aberdeen, UK
  • Raylene Reimer, University of Calgary, Canada
  • Hannah Holscher, University of Illinois at Urbana-Champaign, USA
  • Meghan Azad, University of Manitoba, Canada
  • Mary Ellen Sanders, ISAPP

I have IBS – should I have my microbiome tested?

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

By Prof.  Eamonn Quigley, MD. The Methodist Hospital and Weill Cornell School of Medicine, Houston

I am a gastroenterologist and specialize in what is referred to as “neurogastroenterology” – a rather grandiose term to refer to those problems that arise from disturbances in the muscles or nerves of the gut or in the communications between the brain and the gut.  Yes, the gut has its own nervous system – as elaborate as the spinal cord – which facilitates the two-way communication between the brain and gut.

The most common conditions that I deal with are termed functional gastrointestinal disorders (FGIDs) among which irritable bowel syndrome (IBS) is the most frequent. I have cared for IBS sufferers and been involved in IBS research for decades. But while much progress has been made, IBS continues to be a frustrating problem for many sufferers. No, it will not kill you, but it sure can interfere with your quality of life. Dietary changes, attention to life-style issues (including stress) and some medications can help but they do not help all sufferers all of the time. It is no wonder, therefore, that sufferers look elsewhere for relief. Because, symptoms are commonly triggered by food, there are a host of websites and practitioners offering “food allergy” testing even though there is minimal evidence that food allergy (which is a real problem, causes quite different symptoms and can be fatal) has anything to do with IBS. Nevertheless, sufferers pay hundreds of dollars out of pocket to have these worthless tests performed.

Now as I sit in clinic I am confronted by a new phenomenon – microbiome testing. I cringe when a patient hands me pages of results of their stool microbiome analysis. Has their hard-earned money been well spent? The simple answer is no. Let me explain. First, our knowledge of the “normal” microbiome is still in evolution so we can’t yet define what is abnormal – unless it is grossly abnormal. Second, we have learned that many factors, including diet, medications and even bowel habit can influence the microbiome.  These factors more than your underlying IBS may determine your microbiome test results.  Third, while a variety of abnormalities have been described in the microbiome in IBS sufferers, they have not been consistent. Someday we may identify a microbiome signature that diagnoses IBS or some IBS subgroups – we, simply, are not there yet. Indeed, our group, together with researchers in Ireland and the UK, are currently involved in a large study looking at diet, microbiome and other markers in an attempt to unravel these relationships in IBS.

There have been a lot of exciting developments in microbiome research over the past few years. One that has caused a lot of excitement comes from research studies showing that the microbiome can communicate with the brain (the microbiome-gut-brain axis). It is not too great a leap of faith to imagine how such communications could disturb the flow of signals between and brain and the gut and result in symptoms that typify IBS. We also know that some antibiotics and probiotics can help IBS sufferers. Indeed, about 10% of IBS suffers can date the onset of their symptoms to an episode of gastroenteritis (so-called post-infection IBS). All of this makes it likely that the microbiome has a role in IBS; what we do not know is exactly how. Is the issue a change in the microbiome? Is it how we react to our microbiome? Is it the bacteria themselves or something that they produce? Could our microbiome pattern predict what treatments we will respond to? These are fascinating and important questions which are being actively studied. In the meantime, I feel that microbiome testing in IBS (unless conducted as part of a research study) is not helpful.

 

Related Reading:

Microbiome analysis: hype or helpful?

Why microbiome tests are currently of limited value for your clinical practice

Here’s the poop on getting your gut microbiome analyzed