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Episode 15: A primer on prebiotics

 

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

A primer on prebiotics, with Dr. Karen Scott

Episode summary:

In this episode, the ISAPP podcast hosts talk about prebiotics with Karen Scott, PhD, who is an ISAPP board member and Senior Research Fellow at Rowett Institute, University of Aberdeen, Scotland. Scott describes what prebiotics are, as well as the latest thinking about how they fit within an overall healthy diet and how they confer health benefits through the gut microbiota.

Key topics from this episode:

  • Dr. Scott and colleagues at the Rowett Institute began many years ago by working on anaerobic bacteria from the rumen of animals, then started to focus on the bacteria in the human large intestine.
  • Prebiotics (see definition below) stimulate the growth of beneficial bacteria in the human gut, and in doing so, benefit host health.
    Prebiotics alone cannot guarantee health: they must be consumed in addition to a healthy regular diet, which helps support thediversity of all gut microbes.
  • Prebiotics are not necessarily supplements; they are found in high amounts in many foods such as bulb-based vegetables, banana, and plantain. Around 5g of prebiotic per days is beneficial for health.
  • Not all prebiotics are equal: they each stimulate the growth of particular groups of bacteria. By definition, they must be selectively utilized (that is, some bacteria but not others must use them), and this differentiates prebiotics from fiber.
  • Some prebiotics are shown to improve gut transit (i.e. reduce constipation). One common example of the benefit of prebiotics has to do with bone health: metabolism of prebiotics in the colon tends to lower the pH; this increases calcium absorption for supporting bone health. Other benefits involve the production of short-chain fatty acids.
  • Bifidobacterium have traditionally been a group of bacteria targeted by prebiotics. Some Bifidobacterium produce lactate, and other bacteria produce butyrate (important for colonic health) from lactate. In healthy adults, there are bacteria that are equally or more important than bifidobacteria, however.
  • Prebiotics can target other body sites besides the gut.
  • Prebiotics that can be used by a bacteria in pure culture are not necessarily used by those bacteria within the ecosystem of the human gut.
  • New experimental platforms exist to see which bacteria are producing specific compounds on the growth of a specific substrate. But a model may not represent what is happening in the host, so this must be specifically tested.
  • Human milk oligosaccharides are a great example of how prebiotics are important to human health. Formula is often supplemented with prebiotics because of ample evidence that oligosaccharides (naturally present in human milk, but mimicked synthetically) enable growth of specific bacteria in the baby’s gut that are very important for immunity and other aspects of health.
  • Overall, to support bacteria in your gut and overall health, Dr. Scott recommends consuming a diverse diet: “eat a rainbow”. If you cannot, a prebiotic supplement is advisable.*

Episode abbreviations and links:

Dr. Karen Scott works at the Rowett Institute, a renowned centre focused on nutrition and human health.

ISAPP published the scientific consensus definition of prebiotics.

An early review co-authored by Dr. Scott, covering gut microbiota functions and their impact on host health via diet.

A review on prebiotics to support calcium absorption and therefore bone health.

Dr. Scott refers to a new tool: the Exploris 240 Orbitrap mass spectrometer, which is interfaced with an atmospheric pressure matrix assisted laser desorption ionisation (AP-MALDI) source and direct infusion. This theoretically allows scientists to measure the distribution and composition of complex gut bacterial communities, whilst simultaneously assessing metabolite production from the constituent microbes, allowing them to better understand the cooperation and competition between different human gut microbiota species.

 

Additional resources:

Prebiotics. ISAPP infographic.

Understanding prebiotics and fiber. ISAPP infographic.

The many functions of human milk oligosaccharides: A Q&A with Prof. Ardythe Morrow. ISAPP blog post.

 

About Dr. Karen Scott:

Dr. Karen Scott is a Senior Research Fellow at the Rowett Institute, University of Aberdeen. She leads a research team investigating the (molecular) mechanisms by which key members of the gut microbiota interact with the diet and host, at different life-stages. The fermentation products of gut bacteria contribute to gut health, and are differentially expressed on different substrates, including prebiotics. In vitro bacterial growth studies utilising our large culture collection of gut anaerobes (in pure culture, mixed culture, fermentor systems, and also with human cells) and bioinformatic analyses illustrate niche-specific processes and bacterial interactions. Resident bacteria are also an important reservoir of transferable antimicrobial resistance genes, and other work investigates the evolution and spread of resistance from farm to fork.

Looking back and looking ahead: ISAPP session focuses on the past, present, and future of the biotics field

Kristina Campbell, MSc, and Prof. Dan Tancredi, PhD, Professor of Pediatrics, UC Davis School of Medicine and Center for Healthcare Policy and Research

Twenty years ago, in 2002, the first ISAPP meeting was held in London, Canada. At the time, the field was much less developed: only small human trials on probiotics or prebiotics had been published, no Nutrition and Health Claims legislation existed in the EU, and the human microbiome project hadn’t been conceived.

Now in ISAPP’s 20th year, the scientific landscape of probiotics and prebiotics is vastly different. For one thing, probiotics and prebiotics now form part of the broader field of “biotics”, which also encompasses both synbiotics and postbiotics. Hundreds of trials on biotics have been published, regulations on safety and health claims has evolved tremendously globally, and ”biotics” are go-to interventions (both food and drug) to modulate the microbiota for health.

At the ISAPP annual meeting earlier this year, scientists across academia and industry joined together for an interactive session discussing the past, present and future of the biotics field. Three invited speakers set the stage by covering some important advancements in the field. Then session chair (Prof. Daniel Tancredi) invited the participants to divide into 12 small groups to discuss responses to a set of questions. The session was focused on generating ideas, rather than achieving consensus.

The following is a summary of the main ideas generated about the past, present and future of the biotics field. Many of the ideas, naturally, were future-focused – participants were interested in how to move the field of biotics forward with purpose.

The past 20 years in the biotics field

Prof. Eamonn Quigley had the challenge of opening the discussion about the past by summing up the last 20 years in the biotics field. He covered early microbiological progress in the biotics field, such as the production of antimicrobials and progress in understanding the biology of lactic acid bacteria and their phages. In the modern era, scientists made strides in understanding the role of gut bacteria and metabolites in hepatic encephalopathy; the role of C. difficile in pseudo-membranous colitis; and in the 90s, the concept of bacterial translocation in the intestines. Prof. Quigley summarized the progress and challenges in advancing the underlying science and in developing actionable clinical evidence. He noted that more high-quality clinical trials are being published lately.

The discussion participants noted the following achievements in the field over the past two decades:

Recognition that microbes can be ‘good’. A massive shift in public consciousness has taken place over the past 20 years: the increased recognition that microorganisms are not just pathogens, they have a role to play in the maintenance of health. This added impetus to the idea that consuming beneficial microbes or other biotics is desirable or even necessary.

The high profile of biotics. An increasing number of people are familiar with the basic idea of biotics. Especially for probiotics, there is a strong legacy of use for digestive health; they are also widely available to consumers all around the world.

ISAPP’s published papers. Participants appreciated the papers published as a result of ISAPP’s efforts, including the five scientific consensus definition papers. These have raised the profile of biotics and clarified important issues.

Connections between basic and clinical scientists. Collaborations between biotics scientists and clinicians have been increasing over the past two decades, leading to better questions and higher quality research. ISAPP is one of the leading organizations that provides opportunities for these two groups to interact.

These were among the challenges from the past two decades, as identified by discussion participants:

Lack of understanding among those outside the probiotic/prebiotic field. Although the science has advanced greatly over the past 20 years, some outside the biotics field continue to believe the evidence for probiotic efficacy is thin. It appears some early stereotypes about probiotics and other biotics persist, especially in some clinical settings. This also leads to consumer misunderstandings and affects how they use biotics substances.

Too many studies lacking in quality. In the past, many studies were poorly designed; and sometimes the clinical research did not follow the science. Further, a relative lack of mechanistic research is evident in the literature.

Lack of regulatory harmony. Probiotics and other biotics are regulated in different ways around the world. The lack of harmonized regulations (for example, EFSA and FDA having different regulatory approaches) has led to confusion about how to scientifically substantiate claims in the proper way to satisfy regulators.

Lack of standardized methodologies. Many scientific variables related to biotics, such as microbiome measurements, do not have standardized methodologies, making comparability between studies difficult.

Not having validated biomarkers. The absence of validated biomarkers was noted as a potential impediment to conducting feasible clinical research studies.

The current status of the biotics field

At the moment, the biotics field is more active than ever. The industry has grown to billions of dollars per year and microbial therapeutics are in development all across the globe. The number of published pro/prebiotic papers is over 40K and the consensus definitions alone have been accessed over half a million times.

Prof. Kristin Verbeke spoke at the interactive session about the biotics field at present. She noted that the field has faced the scientific reality that there is no single microbiota configuration exclusively associated with health. The current trajectory is to develop and expand systems biology approaches for understanding the taxonomic and functional composition of microbiomes and how those impact health. Scientists are increasingly making use of bioinformatics tools to improve multi-omic analyses, and working toward proving causation.

The future of the biotics field

Prof. Clara Belzer at the ISAPP 2022 annual meeting

Prof. Clara Belzer spoke on the future of the biotics field, focusing on a so-called “next-generation” bacterium, Akkermansia muciniphila. She covered how nutritional strategies might be based on improved understanding of the interplay between microbes and mucosal health via mucin glycans, and the potential for synthetic microbial communities to lead to scientific discoveries in microbial ecology and health. She also mentioned some notable citizen science education and research projects, which will contribute to overall knowledge in the biotics field.

Participants identified the following future directions in the field of biotics:

Expanding biotics to medical (disease) applications. One group discussed at length the potential of biotics to expand from food applications (for general overall health) to medical applications. The science and regulatory frameworks will drive this shift. They believed this expansion will increase the credibility of biotics among healthcare practitioners, as the health benefits will be medical-condition-specific and will also have much broader applicability.

As for which medical conditions are promising, the group discussed indications for which there are demonstrated mechanistic as well as clinical effects: atopic diseases, irritable bowel syndrome, and stimulating the immune system to boost vaccine efficacy. In general, three different groups of medical conditions could be targeted: (1) common infections, (2) serious infectious diseases, and (3) chronic diseases for which drugs are currently inadequate, such as metabolic disorders, mental health disorders and autoimmune diseases.

Using biotics as adjuncts to medical treatments. An area of huge potential for biotics is in complementing existing medical treatments for chronic disease. There is evidence suggesting in some cases biotics could be used to increase the efficacy of drugs or perhaps reduce side effects, for example with proton pump inhibitors, statins, NSAIDs, metformin, or cancer drugs. Biotics are not going to replace commonly used drugs, but helping manage certain diseases is certainly within reach.

Using real-world data in studies. Participants said more well-conducted studies should be done using real world data. This seems in line with the development of citizen science projects as described by Clara Belzer and others at the ISAPP meeting. Real-world data is particularly important in the research on food patterns/dietary habits as they relate to biotics.

Considering new probiotic formulations. In some cases, a cocktail of many strains (50-60, for example) may be necessary for achieving a certain health effect. Using good models and data from human participants, it may be possible to create these multi-strain formulations with increased effects on the gut microbial ecosystem and increased efficacy.

Embracing omics technology and its advancement. Participants thought the next five years should see a focus on omics data, which allows for stratifying individuals in studies. This will also help increase the quality of RCTs.

More mechanism of action studies. Several groups expressed the importance of investing in understanding mechanisms of action for biotic substances. Such understandings can help drive more targeted clinical studies, providing a rationale for the exact type of intervention that is likely to be effective. Thus, clinical studies can be stronger and have more positive outcomes.

Increased focus on public / consumer engagement. Educational platforms can engage consumers, providing grassroots support for more research resources as well as advancing regulatory frameworks. Diagnostic tools (e.g. microbiome tests with validated recommendations) will help drive engagement of consumers. Further, science bloggers are critical for sharing good-quality information, and other digital channels can have great impact.

Defining and developing “precision biotics”. One group talked about “precision biotics” as solutions that target specific health benefits, which also have a well-defined or unique mechanism of action. At present, this category of biotics is in its very early stages; a prerequisite would be to better define the causes and pathways of gastrointestinal diseases.

Increasing incentives for good science. Participants discussed altering the regulatory and market environments so that good science and proper randomized, controlled trials on biotics are incentivized. Regulators in particular need to change their approaches so that companies are driven primarily by the science.

Precise characterization of responders and non-responders. The responder and non-responder phenomenon is seen with many biotic interventions. Across the field, deep characterization of subjects using multi-omics approaches with a high resolution is needed to determine what factors drive response and non-response to particular biotics substances.

Overall, participants’ ideas centered around the theme of leaning into the science to be able to create better-quality biotics products that support the health of different consumer and patient groups.

 

Special thanks to the table discussion leaders: Irene Lenoir-Wijnkoop, Zac Lewis, Seema Mody, David Obis, Mariya Petrova, Amanda Ramer-Tait, Delphine Saulnier, Marieke Schoemaker, Barry Silkington, Stephen Theis, Elaine Vaughan and Anisha Wijeyesekera.

Episode 14: Evidence on probiotics for preterm infants

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Evidence on probiotics for preterm infants, with Dr. Geoffrey A. Preidis

Episode summary:

In this episode, the ISAPP podcast hosts talk about probiotics for preterm infants with Geoff Preidis, MD, PhD, a pediatric gastroenterologist and researcher at Baylor College of Medicine & Texas Children’s Hospital. Predis describes the evidence on probiotics for prevention of necrotizing enterocolitis, the challenges in interpreting the evidence that exists, and using the evidence to make clinical decisions.

Key topics from this episode:

  • Dr. Preidis works mostly with preterm infants, a population that didn’t exist just a few decades ago.
  • In the totality of evidence on probiotics for treating or preventing certain health conditions, the largest body of evidence is on whether probiotics can prevent negative health outcomes in preterm infants. Large meta-analyses (>15,000 preterm infants, >60 RCTs) conclude that overall, probiotics reduce the risk of necrotizing enterocolitis (NEC) by ~50%.
  • Probiotics do not appear to increase the risk of sepsis. In one case, contamination during the manufacturing process led to a severe infection and death. Although there is a very low risk of this happening, it highlights that a pharmaceutical grade probiotic is not available to give infants.
  • Many caveats accompany these findings, however. Trials use a wide range of products, as well as different strains, doses, durations of treatment, preterm infant populations, etc. Trials vary in their quality.
  • The body of evidence on probiotics for preventing NEC is convincing but far from perfect. Future trials need to continue reporting details on safety.
  • Some leading professional societies have issued guidelines that contradict each other.
  • How should clinicians make a decision, then? One way of choosing one therapy over another is to use network meta-analysis, which  ranks therapies according to which product might have greater efficacy than another. However, the most studied therapies tend to rank higher. 
  • Another way to make a decision is to consider looking at mechanisms. This is challenging with NEC, since we don’t know exactly what causes it.
  • Dr. Preidis is doing research on the association between early life undernutrition and increased risk of metabolic disorders later in life, what is known as the “thrifty phenotype” hypothesis. The mechanism may involve an epigenetic switch, whereby early life nutritional insult affects gene expression and metabolism in a long-lasting way.

 

Episode abbreviations and links:

This 2020 Cochrane Library review of probiotics for preventing NEC, mortality, and invasive infection (i.e. sepsis), found that “Combined analyses showed that giving very preterm and very low birth weight infants probiotics may reduce the risk of necrotizing enterocolitis, and probably reduces the risk of death and serious infection,” but also noted important concerns about the quality of the trials used to support these conclusions,  that, “further, large, high-quality trials are needed to provide evidence of sufficient quality and applicability to inform policy and practice.”

Study in JPGN showing metabolites and fecal microbiota in preterm infants are modulated according to the probiotics they are exposed to.

Network meta-analysis on how probiotics affect morbidity and mortality in preterm infants.

A recent commentary by Dr. Preidis on rational selection of a probiotic for preventing necrotizing enterocolitis

 

Additional resources:

Probiotics and Necrotizing Enterocolitis. ISAPP infographic.

Probiotics to Prevent Necrotizing Enterocolitis: Moving to Evidence-Based Use. ISAPP blog.

 

About Dr. Geoff Preidis:

Dr. Preidis received his undergraduate degree in Physics from Harvard University, then completed his medical degree, residency in Pediatrics, fellowship in Pediatric Gastroenterology, Hepatology & Nutrition, and Ph.D. in Translational Biology and Molecular Medicine from Baylor College of Medicine. Now an Assistant Professor at Baylor College of Medicine and Texas Children’s Hospital, Dr. Preidis leads the Nutritional Physiology Research Laboratory and serves as an attending physician on both the Neonatal Gastroenterology, Hepatology & Nutrition Consultation Service and the Transplant Hepatology Service.

Dr. Preidis’s laboratory seeks to define mechanisms through which early life malnutrition impairs intestinal and liver function, leading to both short-term and long-term medical problems. Current studies focus on how malnutrition slows gastrointestinal motility, alters the gut microbiome, and inhibits the liver’s ability to synthesize important substances including bile acids – all of which adversely impact child growth. This research aims to help children suffering from nutritional deficiencies caused by a wide range of medical and socioeconomic factors, including premature newborns in the neonatal intensive care unit.

Episode 13: The history of ISAPP

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

The history of ISAPP, with Drs. Glenn Gibson, Mary Ellen Sanders and Irene Lenoir-Wijnkoop

Episode summary:

In this episode, the ISAPP podcast hosts talk about the history of the ISAPP organization with the organization’s three co-founders: Glenn Gibson, Mary Ellen Sanders and Irene Lenoir-Wijnkoop. The three guests recount the origins of ISAPP and the state of probiotic and prebiotic science 20 years ago when the organization was founded. They speak about some of the successes and challenges they encountered along the way, and highlight what they see as some of the key achievements of ISAPP.

Key topics from this episode:

  • The origin of the idea for ISAPP back in 1999: an organization dedicated to the science of pro- and prebiotics.
  • The annual meeting proved a key mechanism to gathering the multi-disciplinary scientists together to talk about and advance the science.
  • How ISAPP walks the line between receiving funding from industry members yet protecting scientific credibility.
  • The value that ISAPP has provided to industry members and the academic scientific community over the years.
  • How research in the field developed in the last 20 years and the questions that remain unanswered.
  • How industry members understood the importance of science 20 years ago and still do today, respecting the line between science and marketing.
  • Challenges from the last 20 years and where the field is going.

 

About Irene Lenoir-Wijnkoop:

Irene Lenoir-Wijnkoop is affiliated with the Utrecht University, specialized in public health nutrition and she provides independent consultancy services in related areas. She acts as associate editor in the Drugs Outcomes Research & Policies section of Frontiers. Through her passion for tackling preventable food-related diseases, which jeopardize healthcare resources, societies and human equity, she pioneered the field of nutrition economics.

After a first experience in clinical nutrition, she successively held assignments at the Dutch and the French subsidiaries of The Upjohn Company. When food industries initiated clinical research activities, she joined management and executive positions at the Danone Group. Besides her responsibilities, she got actively involved in ILSI Europe, in many international societies and advisory boards, primarily in the field of probiotics. She co-conceived ISAPP by enabling the first -seminal- meeting in 1999 in New York. In 2010 she was awarded with the Elie Metchnikoff Prize of Recognition.

 

About Mary Ellen Sanders:

Mary Ellen Sanders, PhD serves as the Executive Science Officer for the International Scientific Association of Probiotics and Prebiotics. She is also a consultant in the area of probiotic microbiology (www.mesanders.com). She is the current chair of the United States Pharmacopeia’s Probiotics Expert Panel, was a member of the working group convened by the FAO/WHO that developed guidelines for probiotics, and co-chairs the World Gastroenterology Organisation Guidelines Committee for practice guidelines for the use of probiotics and prebiotics for gastroenterologists. She lives in Colorado with her husband, where she enjoys her 2 grandchildren, hiking and riding her aging Morgan horse.

 

About Glenn Gibson:

Born in an ambulance parked on a roundabout outside Littlethorpe Maternity Hospital near Sunderland, UK (his dad fainted). Failed scientist at school – a trait he has successfully continued to this very day. Has poked around in people’s faeces for over 30 years and as a result, has published over 500 research papers but do not waste your time reading any of them, as you will learn nothing. Before that he did a PhD on sediment microbiology and learnt a lot about what the great population (or poopulation) of Dundee flush down their toilets. 

He has supervised over 80 PhD students and 40 postdocs, who all said he was an absolute pleasure to work with and they wished their projects had lasted 10 times as long as they did. He is a compulsive fantasist. He thinks h-factor is a hat size. Has not done a day’s work in the last decade, largely because he spends all his time reading refereeing requests from journals he has never heard of, or grant bodies wanting reviews after spending decades bouncing every single one of his*, or conference organisers asking him to travel across the world (at his own expense) to give a talk or chair a session on anything whatsoever. Helped Mary Ellen, Irene and Gregor found the organisation most people call EYE-SAPP. 

Episode 8: The link between digestive symptoms, IBS and the gut microbiota: A gastroenterologist’s perspective

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

The link between digestive symptoms, IBS and the gut microbiota: A gastroenterologist’s perspective, with Prof. Eamonn Quigley

Episode summary:

In this episode, the ISAPP hosts focus their discussion around irritable bowel syndrome (IBS) with Prof. Eamonn Quigley, MD, of Weill Cornell Medical College. Prof. Quigley says patients are increasingly curious about the link between IBS and gut microbiota. He outlines what we know so far about the etiology of IBS, and the evidence for how gut microbiota may contribute to the condition as well as possible interventions that target the gut microbes.

Key topics from this episode:

  • What are the symptoms of IBS?
    The typical symptoms is abdominal pain associated with a disturbance in bowel function which could be diarrhea or constipation, or even alternating between them, depending on the patient.
  • How prevalent is IBS?
    Estimates say 5-10% of all people globally have IBS.
  • What is the etiology of IBS?
    There is no clear cause for IBS identified to date. IBS has been linked to the gut-brain axis (as it often co-occurs with depression and anxiety), gut microbiota, diet, previous gastrointestinal infections (Salmonella, Shigella, Campylobacter infections), and antibiotic use. It is also more common in women.
  • How is IBS treated?
    Approaches have tended to focus on treatment of symptoms: for example, treating the pain or diarrhea. Diet has also become an essential part of IBS treatment. But overall quality of life for IBS patients is of crucial importance. The focus should not be only on treating symptoms but also on improving their quality of life.
  • Are probiotics effective for IBS? A short history and perspective on how to develop probiotics for IBS.
  • Effects of the COVID-19 pandemic and COVID-19 infections in IBS patients – lessons learned from other viral infections. 
  • Is the gut microbiota the “Holy Grail” for gastrointestinal health? We still have a lot to learn, especially regarding clinical applications.

 

Episode abbreviations and links:

FODMAP: fermentable oligosaccharides, disaccharides, monosaccharides and polyols (i.e. types of carbohydrates that are poorly absorbed in the small intestine).

EMA: European Medicines Agency (i.e. the European counterpart of the US Food and Drug Administration)

Study: Lactobacillus and bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles

CME course on digestion and gut microbiota: Android version, iOS version, web version

 

Additional resources:

I have IBS – should I have my microbiome tested? ISAPP blog
The Microbiome — Can it aid in the diagnosis and therapy of irritable bowel syndrome (IBS)? ISAPP blog

 

About Prof. Eamonn Quigley:

Eamonn M M Quigley MD FRCP FACP MACG FRCPI MWGO is David M Underwood Chair of Medicine in Digestive Disorders and Chief of the Division of Gastroenterology and Hepatology at Houston Methodist Hospital. A native of Cork, Ireland, he graduated in medicine from University College Cork. He trained in internal medicine in Glasgow, completed a two-year research fellowship at the Mayo Clinic and training in gastroenterology in Manchester, UK. He joined the University of Nebraska Medical Center in 1986 where he rose to become Chief of Gastroenterology and Hepatology. Returning to Cork in 1998 he served as Dean of the Medical School and a PI at the Alimentary Pharmabiotic Center. He served as president of the American College of Gastroenterology and the WGO and as editor-in-chief of the American Journal of Gastroenterology.

Interests include IBS, gastrointestinal motility and the role of gut microbiota in health and disease. He has authored over 1000 publications and has received awards and honorary titles world-wide. Married for over 40 years to Dr Una O’Sullivan they have 4 children and three grandchildren. Interests outside of medicine include literature, music and sport and rugby, in particular; Dr Quigley remains a passionate supporter of Munster and Irish rugby.

Episode 7: Evidence for probiotic use in pediatric populations

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Evidence for probiotic use in pediatric populations, with Prof. Michael Cabana

Episode summary:

In this episode, the ISAPP hosts discuss probiotics for pediatric populations with Prof. Michael Cabana, MD, MPH, from Albert Einstein College of Medicine and The Children’s Hospital at Montefiore. Prof. Cabana starts by acknowledging the gap between the demand for probiotic interventions and the evidence that currently exists for their efficacy. He gives an overview of the challenges in designing trials on probiotic interventions for children, and summarizes what the evidence shows to date.

Key topics from this episode:

  • A concerning gap exists between the strength of evidence for probiotic interventions in children and the high demand by parents for these interventions.
  • A clinician supports clinical recommendations if they are based on multiple high-quality randomized, controlled trials in different settings. Unfortunately, this level of evidence is often missing for pediatric interventions, including for probiotics.
  • A clinician is less concerned about what regulatory category (drug, supplement) a recommendation falls into, and more about the level of evidence supporting its use.
  • At a minimum, a clinician looks first for evidence of no harm.
  • Conducting clinical trials in children presents many challenges. What are the “5 Ds”, which make clinical studies in children different from those in adults, as described by Forrest in 1997?
  • A lot of adult diseases have roots in childhood, so understanding pediatric health is important not just for kids, but also for adults. Preventing adult disease starts at an early age. This is the ‘delayed payoff’ that Forrest refers to.
  • Compelling evidence exists for probiotic efficacy in children for a few endpoints: colic, antibiotic-associated diarrhea, and necrotizing enterocolitis.
  • When it comes to necrotizing enterocolitis, strong evidence, reproducibility, dose-response, and biological mechanisms are what give clinicians the confidence to use probiotics.
  • An individual patient data meta-analysis (a project that emerged from an ISAPP meeting), enabled combining data from numerous studies that looked at the probiotic L. reuteri DSM17938 given to babies with colic. An overall positive effect was seen. Factors that predicted success in infants were being formula-fed, being younger, and not being on proton pump inhibitors.

 

Episode links:

  • One of many reports on the growing market for probiotic products for infants and children 
  • Information about the 2003 Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) mentioned in the podcast 
  • The 5 “Ds” in Pediatrics mentioned in the podcast
  • The TIPS study mentioned in the podcast is described here and here
  • The meta-analysis on colic mentioned in the podcast

 

Additional resources:

ISAPP Digs Deeper into Evidence on Probiotics for Colic with New Meta-Analysis. ISAPP blog
Probiotics to Prevent Necrotizing Enterocolitis: Moving to Evidence-Based Use. ISAPP blog

 

About Prof. Michael Cabana, MD:

Prof. Michael Cabana, MD, MPH, is a Professor of Pediatrics & the Michael I. Cohen University Chair of Pediatrics at Albert Einstein College of Medicine, as well as Physician-in-Chief, The Children’s Hospital at Montefiore (CHAM). He is also a member of the United States Preventive Services Task Force USPSTF (here), a prestigious appointment for medical personnel to weigh evidence (risk vs. harms) on prevention interventions recommended in the United States. He is a clinical trialist (see the trials listed here), with a focus on allergy in children. He has also conducted trials using probiotic interventions. Prof. Cabana served on the ISAPP board of directors from 2008 to 2018. He has an MD from University of Pennsylvania, an MPH from Johns Hopkins, and an MA in business from Wharton Business School.

Dr. Cabana’s comments do not necessarily reflect the views of the USPSTF.

Episode 6: Mechanisms of action for probiotics

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Mechanisms of action for probiotics, with Prof. Sarah Lebeer

Episode summary:

In this episode, the ISAPP hosts speak with Prof. Sarah Lebeer of University of Antwerp, Belgium, to bring clarity to a commonly misunderstood topic: probiotic mechanisms of action. They discuss how probiotic mechanisms are often multi-factorial and difficult to unravel scientifically. Nevertheless, Prof. Lebeer describes five distinct mechanisms of action by which a probiotic may benefit a host.

See ISAPP’s other podcast episode on mechanisms of action, with Prof. Maria Marco: Why mechanistic research on probiotics is captivating and important.

Key topics from this episode:

  • Probiotics are live microorganisms with documented health benefits; their mode of action is multifactorial.
  • Mechanism of action is crucial in the probiotic field. This knowledge helps scientists understand how probiotics interact with the human host and the microbiota. However, even if mode of action for a strain is known it can be difficult to translate it into measurable outcomes for the host.
  • Probiotics can benefit health by five main mechanisms of action applicable at different body sites (gut, vagina, skin, nose, etc.):
    1. Modulation of microbe-microbe interactions by inhibiting pathogens and promoting beneficial microbes. This is based on the production of metabolically active molecules, such as lactic acid. 
    2. Enhancement of mucosal barrier function through interaction with epithelial cells, promoting the integrity of the barrier. 
    3. Modulation of immune responses by interacting with various immune cells. Interaction with the immune cells is also the clearest strain-specific capacity of probiotics.
    4. Modulation of metabolic responses by modulating insulin resistance or cholesterol metabolism. This mode of action is novel, and research is emerging.
    5. Modulation of neurological signaling pathways. This is also a novel mode of action with new evidence building up.
  • Postbiotics can have similar modes of action, provided the active molecules are not inactivated.

 

Episode links:

The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

 

Graphical summary of 5 main mechanisms of action for probiotics

(Image by Sarah Lebeer. Image copyright.)

 

Additional resources:

Current status of research on probiotic and prebiotic mechanisms of action. ISAPP blog
Importance of understanding probiotic mechanisms of action. ISAPP blog

 

About Prof. Sarah Lebeer:

Sarah Lebeer is a research professor at the Department of Bioscience Engineering of the University of Antwerp, Belgium. She has studied bioscience engineering, with a specialisation in cell and gene technology/food & health and obtained her Master at KU Leuven (Belgium). In 2008, she obtained a PhD degree with a topic on the mode of action of gastro-intestinal probiotics in inflammatory bowel diseases and a scholarship in the team of Prof. Jos Vanderleyden (KU Leuven). After a postdoc on the interaction between lactobacilli, viruses and mucosal immunology, in November 2011, she was offered a tenure track position at the University of Antwerp. Since then, she is leading the Laboratory for Applied Microbiology and Biotechnology of the ENdEMIC research group.

In 2020, she was awarded with an ERC Starting Grant that enables her to gain more in-depth knowledge of the evolutionary history and ecology of lactobacilli (https://www.lebeerlab.com). This rationale was also an important driving force to revise the Lactobacillus genus taxonomy with  a large international consortium. Within the ERC project, Sarah has also launched the Isala citizen-science project to gain new insights in the role of vaginal lactobacilli for women’s health (https://isala.be). Since 2018, Sarah is an academic board member of the International Scientific Association on Probiotics and Prebiotics (www.isappscience.org). Communicating about beneficial microbes and probiotics for experts and laymen is an important inspiration for her daily work. 

Episode 5: Prebiotics for animal health

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Prebiotics for animal health, with Prof. George Fahey

Episode summary:

The hosts discuss prebiotics for animals with Prof. George Fahey, a prominent animal nutrition scientist who is currently Professor Emeritus at University of Illinois. Fahey explains how animal nutrition research relates to human nutrition research, and the changes in the field he has seen over the course of his long career. He describes the research on prebiotics for animal nutrition, covering both livestock and companion animals.

Key topics from this episode:

  • A short history of animal prebiotics research as well as future opportunities in animal nutrition.
  • Pro- and prebiotics are being explored as an alternative to antibiotic treatment in production animals. Antibiotics are overused, leading to an increase in antibiotic resistance; the “biotics” therefore have great potential in animal nutrition.
  • Probiotics can potentially be used instead of antibiotics to inhibit pathogens and support the gut microbiota in animals.
  • Prebiotics possibly have high nutritional value and beneficial effects in animals, especially in poultry and pigs.
  • There are limitations to using prebiotics in the animal industry, especially for some animals such as horses and ruminants.
  • There has been increased use of prebiotics for companion animals (pets) in the past few years. Now many pet foods contain prebiotics.
  • Benefits of using prebiotics in companion animals:
    •  Support digestive health
    •  Improve stool quality
    • Support the gut microbiota, which also translates to good stool quality
  • A short overview of how companion animals’ food is produced, and the timing of adding prebiotics.
  • Wild animals’ diet has low nutrition with limited to no prebiotic intake, resulting in a shorter lifespan in comparison with companion animals
  • Some take-home points from animal models and animal nutrition research.

 

Episode links:

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics
The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

 

Additional resources:

Are prebiotics good for dogs and cats? An animal gut health expert explains. ISAPP blog post
Using probiotics to support digestive health for dogs. ISAPP blog post
Prebiotics. ISAPP infographic

 

About Prof. George Fahey:

George C. Fahey, Jr. is Professor Emeritus of Animal Sciences and Nutritional Sciences at the University of Illinois at Urbana-Champaign. He served on the faculty since 1976 and held research, teaching, and administrative appointments. His research was in the area of carbohydrate nutrition of animals and humans. He published numerous books, book chapters, journal articles, and research abstracts.

He currently serves on two editorial boards, numerous GRAS expert panels, and is scientific advisor to both industry and governmental organizations. He retired from the University in 2010 but continues to serve on graduate student committees and departmental search committees. He owns Fahey Nutrition Consulting, Inc. that provides services to the human and pet food industries.

Episode 4: Weighing evidence for probiotic interventions: Perspectives of a primary care physician

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Weighing evidence for probiotic interventions: Perspectives of a primary care physician, with Prof. Dan Merenstein, MD

Episode summary:

In this episode, the ISAPP host Prof. Dan Tancredi discusses evidence for probiotic interventions with Prof. Dan Merenstein, MD, a family medicine researcher based at Georgetown University. They discuss what it means to practice evidence-based medicine, and what kind of evidence clinicians should look for when deciding whether an intervention is appropriate. Prof. Merenstein shares how probiotic evidence has strengthened in the past few decades, and gives tips on what to look for in a probiotic intervention study.

Key topics from this episode:

  • What is evidence-based medicine, and why is it important to practice it? Evidence-based medicine provides proper care for patients at the appropriate time by focusing on the existing evidence provided by clinical studies.
  • What is evidence, and how do we obtain a high level of evidence for probiotics? Evidence should come from well-designed clinical studies. Animal and in vitro studies provide supportive preclinical information and mechanistic insights.
  • The quality of probiotic research has improved in recent years. Compared with decades ago, studies are more likely to be high quality and more likely to be properly-powered. Such studies have provided a clearer sense of the circumstances under which probiotics may – or may not – provide health benefits.
  • What is the proper way to report clinical trials in the probiotic field? Focus on the rules for conducting a clinical trial: for example, CONSORT (see below). Compliance is also important for good outcomes.
  • How can a clinician evaluate if a patient should use an intervention? The focus should be on the evidence for each intervention, the potential harm of the intervention, and the positive and negative outcomes.
  • Evidence-based medicine also needs to account for regional differences and where the clinical studies have been performed. Evidence about probiotic effects needs to account for microbiome differences and lifestyle differences between countries.
  • For which indications do we now have actionable evidence for probiotic use?
    • Use of certain probiotics together with antibiotic treatment to prevent antibiotic-associated diarrhea
    • Use of an L. reuteri strain to reduce crying time for infants suffering from colic
    • Certain probiotics can help prevent traveler’s diarrhea or treat acute pediatric infectious diarrhea.
    • Probiotics to help with endpoints such as weight loss and metabolic syndrome, for autism and gut-brain indications, for skin conditions such as eczema and acne, and inflammatory bowel disease are active areas of research and soon scientists will have more answers.
  • Probiotic research is improving. Patients are using probiotics, and they are aware of the benefits of probiotics – Prof. Merenstein estimates that 80% of his patients are taking a probiotic. The job of the doctor is to get them to use probiotics in an evidence-based manner.

 

Episode links:

CONSORT (Consolidated Standards of Reporting Trials) establishes a well-accepted, evidence-based, minimum set of recommendations for reporting randomized trials.
IPDMA (individual patient data meta-analysis) – see this Sung et al. paper on infantile colic and L. reuteri
BB12: Bifidobacterium animalis subsp. lactis BB-12, a well-studied probiotic. See this paper.
A priori: without prior knowledge

 

Additional resources:

The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

 

About Prof. Dan Merenstein:

Dr. Daniel Merenstein is a Professor with tenure of Family Medicine at Georgetown University, where he also directs Family Medicine research. Dr. Merenstein has a secondary appointment in the undergraduate Department of Human Science, in the School of Nursing and Health Studies. Dr. Merenstein teaches two undergraduate classes, a research capstone and a seminar class on evaluating evidence based medical decisions. He has been funded by the NIH, USDA, Foundations and Industry, for grants over $100 million. Dr. Merenstein is the President of the board of directors of the International Scientific Association of Probiotics and Prebiotics.

The primary goal of Dr. Merenstein’s research is to provide answers to common clinical questions that lack evidence and improve patient care. Dr. Merenstein is a clinical trialist who has recruited over 2,100 participants for 10 probiotic trials since 2006. He is an expert on probiotics, antibiotic stewardship in outpatient settings and also conducts HIV research in a large women’s cohort. He sees patients in clinic one day a week.

Probiotics vs. prebiotics: Which to choose? And when?

By Dr. Karen Scott, PhD, Rowett Institute, University of Aberdeen, Scotland

As consumers we are constantly bombarded with information on what we should eat to improve our health. Yet the information changes so fast that it sometimes seems that what was good for us last week should now be avoided at all costs!

Probiotics and prebiotics are not exempt from such confusing recommendations, and one area lacking clarity for many is which of them we should pick, and when. In this blog I will consider the relative merits of probiotics and prebiotics for the gut environment and health.

By definition, both probiotics and prebiotics should ‘confer a health benefit on the host’. Since an improvement in health can be either subjective (simply feeling better) or measurable (e.g. a lowering in blood pressure) it is clear that there is not a single way to define a ‘health benefit’. This was discussed nicely in a previous blog by Prof Colin Hill.

Although consumption of both probiotics and prebiotics should provide a health benefit, this does not mean that both need to act through the gut microbiota. Prebiotics definitively need to be selectively utilised by host microorganisms – they are food for our existing microbiota. However, depending on the site of action, this need not be the gut microbiota, and prebiotics targeting other microbial ecosystems in or on the body are being developed. Traditionally prebiotics have specifically been used to boost numbers of gut bacteria such as Bifidobacterium and the Lactobacilliaceae family, but new prebiotics targeting different members of the gut microbiota are also currently being researched.

Probiotics are live bacteria and despite a wealth of scientific evidence that specific probiotic bacterial strains confer specific health benefits, we often still do not know the exact mechanisms of action. This can make it difficult both to explain how or why they work, and to select new strains conferring similar health benefits. Many probiotics exert their effects within the gut environment, but they may or may not do this by interacting with the resident gut microbiota. For instance probiotics that reduce inflammation do so by interacting directly with cells in the mucosal immune system. Yet strains of lactobacilli (see here for what’s included in this group of bacteria) may do this by modulating cytokine production while Bifidobacterium strains induce tolerance acquisition. These very different mechanisms are one reason why mixtures containing several probiotic species or strains may in the end prove the most effective way to improve health. On the other hand, some probiotics do interact with the resident gut microbes: probiotics that act by inhibiting the growth of pathogenic bacteria clearly interact with other bacteria. Sometimes these may be potential disease-causing members of the resident microbiota, normally kept in check by other commensal microbes that themselves have become depleted due to some external impact, and some may be incoming pathogens. Such interactions can occur in the gut or elsewhere in the body.

This brings me back to the original question, and one I am frequently asked – should I take a probiotic or a prebiotic? The true and quick answer to this question is ‘it depends’! It depends why you are asking the question, and what you want to achieve. Let’s think about a few possible reasons for asking the question.

I want to improve the diversity of my microbiota. Should I take a prebiotic or a probiotic?

My first reaction was that there is an easy answer to this question – a prebiotic. Prebiotics are ‘food’ for your resident bacteria, so it follows that if you want to improve the diversity of your existing microbiota you should take a prebiotic. However, in reality this is too simplistic. Since prebiotics are selectively utilised by a few specific bacteria within the commensal microbiota to provide a health benefit, taking a prebiotic will boost the numbers of those specific bacteria. If the overall bacterial diversity is low, this may indeed improve the diversity. However, if the person asking the question already has a diverse microbiota, although taking one specific prebiotic may boost numbers of a specific bacterium, it may not change the overall diversity in a measurable way. In fact the best way to increase the overall diversity of your microbiota is to consume a diverse fibre-rich diet – in that way you are providing all sorts of different foods for the many different species of bacteria living in the gut, and this will increase the diversity of your microbiota.  Of course, if you already consume a diverse fibre-rich diet your microbiota may already be very diverse, and any increased diversity may not be measurable.

I want to increase numbers of bifidobacteria in my microbiota. Should I take a prebiotic or a probiotic?

Again, I initially thought this was easy to answer – a prebiotic. There is a considerable amount of evidence that prebiotics based on fructo-oligosaccharides (FOS or inulin) boost numbers of bifidobacteria in the human gut. But this is only true as long as there are bifidobacteria present that can be targeted by consuming suitable prebiotics. Some scientific studies have shown that there are people who respond to prebiotic consumption and people who do not (categorised as responders and non-responders). This can be for two very different reasons. If an individual is devoid of all Bifidobacterium species completely, no amount of prebiotic will increase bifidobacteria numbers, so they would be a non-responder. In contrast if someone already has a large, diverse bifidobacteria population, a prebiotic may not make a meaningful impact on numbers – so they may also be a non-responder.

However, for those people who do not have any resident Bifidobacterium species, the only possible way to increase them would indeed be to consume a probiotic- specifically a probiotic containing one or several specific Bifidobacterium species. Consuming a suitable diet, or a prebiotic alongside the probiotic, may help retention of the consumed bifidobacteria, but this also depends on interactions with the host and resident microbiota.

I want to increase numbers of ‘specific bacterium x’ in my microbiota. Should I take a prebiotic or a probiotic?

The answer here overlaps with answer 2, and depends on the specific bacterium, and what products are available commercially, but the answer could be to take either, or a combination of both – i.e. a synbiotic.

If bacterium x is available as a probiotic, consuming that particular product could help. If bacterium x has been widely researched, and the specific compounds it uses for growth have been established, identifying and consuming products containing those compounds could boost numbers of bacterium x within the resident microbiota. Such research may already have identified combination products – synbiotics – that could also be available.

One caveat for the answers to questions 2 and 3 is that probiotics do not need to establish or alter the gut microbiota to have a beneficial effect on health. In fact, a healthy large intestine has a microbial population of around 1011-1012 bacterial cells per ml, or up to 1014 cells in total, while a standard pot of yogurt contains 1010 bacterial cells (108 cells/ml). Assuming every probiotic bacterial cell reaches the large intestine alive, they would be present in a ratio of 1: 10,000. This makes it difficult for them to find a specific niche to colonise, so consuming a probiotic may not “increase numbers of ‘specific bacterium x’ in my microbiota”, but this does not mean that the function of the probiotic within the gut ecosystem would not provide a health benefit. Many probiotics act without establishing in the microbiota.

I’ve been prescribed antibiotics. Should I take a prebiotic or a probiotic?

In this case the answer is clear cut – a probiotic.

There is a lot of evidence that consumption of probiotics can alleviate symptoms of, or reduce the duration of, antibiotic associated diarrhoea. From what we know about mechanisms of action, consumption of antibiotics kills many resident gut bacteria, reducing the overall bacterial population and providing an opportunity for harmful bacteria to become more dominant. Consuming certain probiotics can either help boost bacterial numbers in the large intestine, preventing the increased growth in pathogenic bacteria until the resident population recovers, or can increase production of short chain fatty acids, decreasing the colonic pH, preventing growth of harmful bacteria. Ideally probiotics would be taken alongside antibiotics, from day 1, to avoid the increase in numbers of the potentially harmful bacteria in the first place. This has been shown to be more effective. Consuming the probiotic alongside prebiotics that could help the resident microbiota recover more quickly may be even more effective. Even if you’ve already started the course of antibiotics, it’s not too late to start taking probiotics to reduce any side-effects. Always remember to complete taking the course of antibiotics as prescribed.

 

 

Putting all of this together to answer the initial question of whether it’s better to take probiotics or prebiotics, a better answer may in fact be take both to cover the different effects each has, maximising the benefit to health. There are specific times when probiotics are better, and other times when prebiotics are better, and consuming both together may make each more effective. In any case care has to be taken to consume a product that has been confirmed through robust studies to have the specific benefit that is required.

 

Episode 3: The science of fermented foods, part 2

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

The science of fermented foods, part 2, with Prof. Bob Hutkins

Episode summary:

Before listening to this episode, it’s recommended that you check out episode #1, The science of fermented foods, Part 1. In this episode, the hosts continue their discussion of fermented foods with Prof. Bob Hutkins, University of Nebraska – Lincoln. Prof. Hutkins elaborates on how the microbes associated with fermented foods may confer health benefits, as well as how food scientists choose strains for fermentation. He emphasizes how the live microbes in fermented foods differ from probiotics.

Key topics from this episode:

  • Why working in the field of fermented foods is exciting and rewarding
  • The challenges for scientists, especially when it comes to designing clinical studies with various fermented foods
  • The benefits of fermented foods – from being safe as well as nutritious, to the health benefits that live microbes present in the foods can provide
  • How microbes are selected for fermentation; companies focus on strain performance – i.e., good growth and survival to preserve the food and provide a desired flavor and texture
  • The activities of live microbes present in fermented foods, from initiating the fermentation process to benefiting human health
  • The differences between probiotics and live microbes in fermented foods
  • How live microbes in fermented foods might affect your gut microbiota and why some scientists believe that fermented foods are important for getting regular doses of live microbes

 

Episode links:

Microbiology and Technology of Fermented Foods, 2nd Ed., by Robert W. Hutkins
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods
The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic
Gut-microbiota-targeted diets modulate human immune status, study by Stanford researchers

 

Additional resources:

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics.
Postbiotics. ISAPP infographic
Fermented foods. ISAPP infographic
What are fermented foods? ISAPP video
Do fermented foods contain probiotics? ISAPP blog post
How are probiotic foods and fermented foods different? ISAPP infographic
Are fermented foods probiotics? Webinar by Mary Ellen Sanders, PhD

 

About Prof. Bob Hutkins:

Bob Hutkins is the Khem Shahani Professor of Food Microbiology at the University of Nebraska. He received his Ph.D. from the University of Minnesota and was a postdoctoral fellow at Boston University School of Medicine. Prior to joining the University of Nebraska, he was a research scientist at Sanofi Bio Ingredients.

The Hutkins Lab studies bacteria important in human health and in fermented foods. His group is particularly interested in understanding factors affecting persistence and colonization of probiotic bacteria in the gastrointestinal tract and how prebiotics shift the intestinal microbiota and metabolic activities. The lab also conducts clinical studies using combinations of pro- and prebiotics (synbiotics) to enhance health outcomes. More recently we have developed metagenome-based models that can be used in personalized nutrition.

Professor Hutkins has published widely on probiotics, prebiotics, and fermented foods and is the author of the recently published 2nd edition of Microbiology and Technology of Fermented Foods.

Episode 2: Why mechanistic research on probiotics is captivating and important

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Why mechanistic research on probiotics is captivating and important, with Prof. Maria Marco

Episode summary:

In this episode, the ISAPP hosts discuss probiotic mechanisms of action with Prof. Maria Marco, University of California, Davis. Prof. Marco is a well-known probiotic researcher with special expertise in food-associated lactobacilli. Here she explains how studying probiotics in food science can lead to fundamental insights in biology. She shares why it’s important to understand probiotic mechanisms of action, and describes how scientists go about identifying which compounds or pathways are important for probiotic health effects.

Key topics from this episode:

  • The search for probiotic mechanisms of action: why this research is essential and the added value of this type of research for the end consumer.
  • What we now understand about probiotic mode of action: probiotic mode of action for different strains is mediated by multiple working mechanisms, from cell-wall-associated molecules to bacteriocin production and metabolite synthesis.
  • How researchers set the stage for studying probiotics’ mode of action, from large scale screening, to molecular techniques focusing on single molecules and genome comparisons between strains.
  • Whether we need to apply something similar to Koch’s postulates when talking about the effects of probiotics.
  • The potential effects of food or delivery matrix on a probiotic mechanism of action.  
  • What we can learn from the postbiotic research, which can help inform probiotic mechanisms of action.
  • The most exciting developments in probiotic mode of action research in the past 10 years and the future of this area of research.

 

Episode links:

The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic
Prof. Marco refers to two of her mentors, Willem De Vos and Michiel Kleerebezem
See this overview of Koch’s postulates

 

Additional resources:

Bacterial genes lead researchers to discover a new way that lactic acid bacteria can make energy and thrive in their environments, ISAPP blog post featuring recent work from Prof. Marco’s lab

 

About Prof. Maria Marco:

Maria Marco is a Professor in the Department of Food Science and Technology and Chair of the Food Science Graduate Group at the University of California, Davis. She received her PhD in microbiology from the University of California, Berkeley and then was a postdoc and project leader at NIZO Food Research, The Netherlands. Dr. Marco has 20 years’ experience investigating fermented foods, probiotics, and diet-dependent, host-microbe interactions in digestive tract. Her laboratory at UC Davis is broadly engaged in the study of food and intestinal microbiomes and the ecology and genetics of lactic acid bacteria. 

Episode 1: The science of fermented foods, part 1

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 Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

The science of fermented foods, part 1, with Prof. Bob Hutkins

Episode summary:

The hosts discuss fermented foods with Prof. Bob Hutkins, University of Nebraska – Lincoln. Prof. Hutkins wrote a popular textbook on fermented foods and has had a 40-year career in fermentation science. He shares why he ended up in fermentation science, as well as how fermented foods are made and how important live microbes are for their health benefits.

Key topics from this episode:

  • What fermented foods are
  • The scientific consensus definition published by ISAPP
  • Fermentation processes and practices used in early times and still used today
  • The benefits and safety of fermented foods, as well as the difference between fermentation and food spoilage
  • The live microbes present in fermented foods, how many are present, and their potential health benefits
  • Why some fermented foods have live microbes and others do not; and how even when live microbes are absent due to heat treatment, for example, these products may still be classified as fermented 
  • The differences between fermented foods, probiotics, and probiotic fermented foods

 

Episode links:

Microbiology and Technology of Fermented Foods, 2nd Ed., by Robert W. Hutkins
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods
The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic
Synbiotics: Definitions, Characterization, and Assessment – ISAPP webinar featuring Prof. Bob Hutkins and Prof. Kelly Swanson

 

Additional resources:

Fermented foods. ISAPP infographic
What are fermented foods? ISAPP video
Do fermented foods contain probiotics? ISAPP blog post
How are probiotic foods and fermented foods different? ISAPP infographic
Are fermented foods probiotics? Webinar by Mary Ellen Sanders, PhD

 

About Prof. Bob Hutkins:

Bob Hutkins is the Khem Shahani Professor of Food Microbiology at the University of Nebraska. He received his Ph.D. from the University of Minnesota and was a postdoctoral fellow at Boston University School of Medicine. Prior to joining the University of Nebraska, he was a research scientist at Sanofi Bio Ingredients.

The Hutkins Lab studies bacteria important in human health and in fermented foods. His group is particularly interested in understanding factors affecting persistence and colonization of probiotic bacteria in the gastrointestinal tract and how prebiotics shift the intestinal microbiota and metabolic activities. The lab also conducts clinical studies using combinations of pro- and prebiotics (synbiotics) to enhance health outcomes. More recently we have developed metagenome-based models that can be used in personalized nutrition.

Professor Hutkins has published widely on probiotics, prebiotics, and fermented foods and is the author of the recently published 2nd edition of Microbiology and Technology of Fermented Foods.

Do fermented foods contain probiotics?

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.

 

ISAPP board members give a scientific overview of synbiotics in webinar

Many kinds of products are labeled as synbiotics – but how do they differ from each other? And do they all meet the scientific criteria for synbiotic ingredients?

To demystify the science of synbiotics – including ISAPP’s definition published in 2020 – ISAPP is holding a free webinar: Synbiotics: Definitions, Characterization, and Assessment. Two ISAPP board members, Profs. Bob Hutkins and Kelly Swanson, present on the implications of the synbiotic definition for science and industry. They clarify the difference between ‘complementary’ and ‘synergistic’ synbiotics and cover the basics of meeting the criteria for synbiotic efficacy and safety. One challenge is learning when a synbiotic is required to have demonstrated both selective utilization of the microbiota in the same study that measures the health outcome. A Q&A is scheduled for the last 20 minutes of the webinar.

This webinar is for scientists, members of the public, and media who want a scientific overview on synbiotics as they appear in more and more consumer products.

The live webinar was broadcast on Friday, January 28th, 2022, from 10:00 am – 11:10 New York (Eastern) time.

Find the webinar recording here.

Research on the microbiome and health benefits of fermented foods – a 40 year perspective

By Prof. Bob Hutkins, PhD, University of Nebraska Lincoln, USA

Many ISAPPers remember when fermented foods attracted hardly any serious attention from scientists outside the field. Certainly, most clinicians and health professionals gave little notice to fermented foods. In the decades before there were artisan bakeries and microbreweries proliferating on Main Street USA, even consumers did not seem very interested in fermented foods.

When I began my graduate program at the University of Minnesota in 1980, I was very interested in microbiology, but I did not know a lot about fermented foods. Accordingly, I was offered two possible research projects. One involved growing flasks of Staphylococcus aureus, concentrating the enterotoxins, feeding that material to lab animals, and then waiting for the emetic response.

My other option was to study how the yogurt bacterium, Streptococcus thermophilus, metabolized lactose in milk. This was the easiest career choice ever, and the rest, as they say, is history.

Indeed, that lab at Minnesota was one of only a handful in North America that conducted research on the physiology, ecology, and genetics of microbes important in fermented foods. Of the few labs in North America delving into fermented foods, most emphasized dairy fermentations, although some studied vegetable, meat, beer, wine, and bread fermentations. Globally, labs in Europe, Japan, Korea, Australia, and New Zealand were more engaged in fermented foods research than we were in North America, but overall, the field did not draw high numbers of interested researchers or students.

That’s not to say there weren’t exciting and important research discoveries occurring. Most research at that time was focused on the relevant functional properties of the microbes. This included carbohydrate and protein metabolism, flavor and texture development, tolerance to acid and salt, bacteriocin production, and bacteriophage resistance. Despite their importance, even fewer labs studied yeasts and molds, and the focus was on lactic acid bacteria.

Other researchers were more interested in the health benefits of fermented foods. Again, yogurt and other cultured dairy foods attracted the most interest. According to PubMed, there were about 70 randomized clinical trials (RCTs) with yogurt as the intervention between 1981 and 2001. Over the next 20 years, there were more than 400 yogurt RCTs.

Fast forward a generation or two to 2021, and now fermented foods and beverages are all the rage. Certainly, having the molecular tools to sequence genomes and interrogate entire microbiomes of these foods has contributed to this new-found interest. Scanning the recent literature, there are dozens of published papers on microbiomes (and metabolomes) of dozens of fermented foods, including kombucha (and their associated symbiotic cultures of bacteria and yeast, known as SCOBYs), kefir, kimchi, beer (and barrels), cheese (and cheese rinds), wine, vinegar, miso and soy sauce, and dry fermented sausage.

It’s not just fermentation researchers who are interested in fermented foods. For ecologists and systems biologists, fermented foods serve as model systems to understand succession and community dynamics and how different groups of bacteria, yeast, and mold compete for resources.

Moreover, consumers can benefit when companies that manufacture fermented foods take advantage of these tools. The data obtained from fermented food microbiota analyses can help to correlate microbiome composition to quality attributes or identify potential sources of contamination.

Importantly, it is also now possible to screen microbiomes of fermented foods for gene clusters that encode potential health traits. Indeed, in addition to microbiome analyses of fermented foods, assessing their health benefits is now driving much of the research wave.

As mentioned above, more than 400 yogurt RCTs were published in the past two decades, but alas, there were far fewer RCTs reported for other fermented foods. This situation, however, is already changing. The widely reported fiber and fermented foods clinical trial led by Stanford researchers was published in Cell earlier this year and showed both microbiome and immune effects. Other RCTs are now in various stages, according to clinicaltrials.gov.

Twenty years ago, when ISAPP was formed, I suspect few of us would have imagined that the science of fermented foods would be an ISAPP priority. If you need proof that it is, look no further than the 2021 consensus paper on fermented foods. It remains one of the most highly viewed papers published by Nature Reviews Gastroenterology and Hepatology.

Further evidence of the broad interest in fermented foods was the recently held inaugural meeting of The Fermentation Association. Participants included members of the fermented foods industry, culture suppliers, nutritionists, chefs, food writers, journalists, retailers, scientists and researchers.

Several ISAPP board members also presented seminars, including this one who remains very happy to have made a career of studying fermented foods rather than the emetic response of microbial toxins.

Pharmacists as influencers of probiotic use

By Kristina Campbell, science writer

It’s not an uncommon scene in a pharmacy: someone standing in front of the shelf of probiotic products, picking up various bottles and reading the labels, looking uncertain. The person’s doctor may have recommended a certain brand of probiotic to prevent diarrhea with a prescribed course of antibiotics—but they’ve just noticed that the store-brand probiotic, with different strains, is half the price.

Dragana Skokovic-Sunjic

According to Dragana Skokovic-Sunjic, clinical pharmacist and author of the ‘Clinical Guide to Probiotic Products Available in Canada/US’, pharmacists can play an important and influential role helping patients make informed decisions about the available products. “Pharmacists provide a ‘last check validation’ before the patient actually decides to purchase a product,” she says. “And we proactively seek to assist those patients who need help.”

Nardine Nakhla

Nardine Nakhla, clinical pharmacist and Clinical Lecturer at the University of Waterloo School of Pharmacy, says pharmacists often have the knowledge and experience to zero in on which over-the-counter product(s) will or will not work for a certain individual. “Pharmacists have the knowledge and skills to individualize the recommendation based on patient-specific and disease-specific factors, and that is so very important with non-prescription and natural health products because there is no one-size-fits-all approach,” she says.

Can pharmacists apply their knowledge and skills to make specific probiotic recommendations? While it can be hard to narrow the evidence down on specific products, pharmacists can certainly play a role in helping patients understand the evidence for the products they encounter. In a recent interview with ISAPP, Skokovic-Sunjic and Nakhla explained why pharmacists in Canada and elsewhere have the potential to steer people’s choice of over-the-counter and natural health products – including probiotics.

Pharmacists have knowledge about the products on their shelves.

“Advising patients on self-care, which includes over-the-counter and natural health product use, is a key responsibility of Canadian pharmacists. We have North American survey data that shows, for patients who go out and buy non-prescription and natural health products, over 80% never read the label,” says Nakhla.

This means that having a pharmacist available at the point-of-purchase to answer questions can go a long way toward educating people about what’s actually in their hands and how to optimize use, if warranted.

“Having the pharmacist present lets you access somebody who can help inform your decisions—someone who can perhaps steer you away from products that may not be appropriate for you,” she says.

“Pharmacists need to be familiar with the products they are selling at their pharmacies,” adds Skokovic-Sunjic. “They are skilled at asking suitable questions to ensure the patient’s needs and wishes are understood and then to help them choose appropriate over-the-counter, ‘self-selection’ therapy.”

Pharmacists are unique in having non-prescription products within their standards of practice.

As a faculty member at the school of pharmacy, Nakhla emphasizes the requirement for pharmacists to know how to assess and manage patients seeking self-care in the community. She says, “We have a unique body of knowledge where we study non-prescription therapeutics and other self-care measures of disease management and health maintenance,” she says. “Pharmacists are trained to know about these and to recommend evidence-based and cost-effective measures individualized for each patient.”

“It’s explicitly stated under our Standards of Practice that we must be proficient in providing information on non-prescription products, natural health products, and on non-pharmacological measures to enable patients to receive the intended benefit of the therapies, whereas physicians are far more focused on the diagnosis and prescription therapies,” she says.

Pharmacists can identify patients who could benefit from probiotics

Both Nakhla and Skokovic-Sunjic emphasize that pharmacists frequently identify people who could potentially benefit from self-care products, even if they don’t come in looking for them.

Nakhla mentions the probiotic guide authored by Skokovic-Sunjic, and how it helps pharmacists provide helpful solutions to common problems that present in the community. “I think a good strategy is looking at the conditions listed in the probiotic guide and the subsequent products indicated for use for them, and then work backwards to try to identify patients who may benefit from the listed therapies, rather than just wait for them to present asking you questions.”

Pharmacists are in a position to encourage prevention.

“Pharmacy has historically focused on providing reactive healthcare rather than proactive or preventative care,” says Nakhla. But this has recently changed, with a growing emphasis on preventing chronic disease through ongoing health maintenance and self-care strategies. She cites pharmacists as qualified health professionals who encounter many generally healthy people throughout the course of their day, and who are therefore well-positioned to advise the public on how to remain healthy.

Skokovic-Sunjic gives some examples: “If the consumer will be travelling, we might suggest a specific probiotic to prevent traveller’s diarrhea. Or if we are coming to the cold and flu season, we may recommend a product they can take to reduce the risk of developing common infectious diseases.”

Pharmacists can conduct brief or lengthy assessments before providing recommendations.

Skokovic-Sunjic says, “A pharmacist can provide specific recommendations that could really make a big difference in the patient’s experience by quickly asking a few targeted questions. This strategy may save the patient time, money, frustration and sub-optimal health outcomes. When consumers self-select inappropriate products, they will not experience benefits they seek. Determined to choose a natural product, some consumers will try a second or even third product but will not get the symptom relief they are looking for. An unintended consequence of this is that the patient may dismiss the probiotics as ineffective not because they did not work, but because it was the wrong product for the desired effect.”

Brief assessment questions are especially important for probiotics, she adds, because specificity can ‘make or break’ how useful they are to an individual. “In my consultations with patients, I quite often include questions about bowel movements and I know they are questioning why I am asking. Understanding gut function can be extremely helpful in providing appropriate probiotic recommendations.”

Pharmacists can help people understand the concept of ‘evidence-based’.

Nakhla acknowledges it’s difficult for the average person to confront a shelf of probiotic products and delineate between the ones that have evidence backing their use, and the ones that do not. “That’s where I really think a pharmacist needs to intervene and to help them balance out the pros and the cons,” she says.

“If patients are looking for a probiotic to relieve a specific symptom, then looking for an evidence-based recommendation for that specific symptom is needed,” says Skokovic-Sunjic. “If they pick something that’s not supported by evidence, it may not provide symptom relief or the benefit they expect. This may be in addition to wasted funds and mounting frustration.”

Thus, pharmacists are in a unique position to contribute to enhanced awareness about efficacy and “evidence-based self-care” as they explain these concepts to consumers at the point of sale.

 

Given all the potential ways for pharmacists to guide consumer decisions about probiotics, both Skokovic-Sunjic and Nakhla agree that keeping up on the latest probiotic evidence is of high importance.

Through ISAPP’s new efforts to engage with pharmacists, the organization plans to gauge how pharmacists in various parts of the world approach probiotic recommendations, and to support the ‘best case scenario’ of pharmacists providing evidence-based information about probiotics directly to consumers.

Sign up here for ISAPP’s newsletter for pharmacists.

What’s the evidence on ‘biotics’ for health? A summary from five ISAPP board members

Evidence on the health benefits of gut-targeted ‘biotics’ – probiotics, prebiotics, synbiotics, and postbiotics – has greatly increased over the past two decades, but it can be difficult to sort through the thousands of studies that exist today to learn which of these ingredients are appropriate in which situations. At a recent World of Microbiome virtual conference, ISAPP board members participated in a panel that provided an overview of what we currently know about the health benefits of ‘biotics’ and how they are best used.

Here’s a summary of what the board members had to say:

Dr. Mary Ellen Sanders: Probiotics and fermented foods

  • Probiotics are “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”.
  • Unfortunately, published assessments of probiotic products available on the market show that these products often fall short of required evidence. For example, their labels may not adequately describe the contents (including genus / species / strain in the product); they may not guarantee the efficacious dose through the end of the shelf life.
  • Contrary to common belief, probiotics do not need to colonize in the target site (e.g. the gut), impact gut microbiota composition, be derived from humans, or be resistant to stomach acid and other gut secretions such as bile.
  • Fermented foods are those made “through desired microbial growth and enzymatic conversions of food components”. The recent increased interest in fermented foods may come from people’s increased awareness of the role of gut microbes in overall health, but it is important to note that we have little direct evidence that the transient effects of fermented food microbes on the gut microbiota actually lead to health benefits. With that said, observational studies suggest that consuming some traditional fermented foods is associated with improved health outcomes.

Prof. Dan Merenstein, MD: Probiotics – How do I know what to prescribe for adult health?

  • A (limited) survey showed that most dietary supplement probiotic products cannot be linked to evidence because they do not provide enough information to determine what evidence exists to support their use – especially strains in the product. However, there are some probiotic products that have robust evidence.
  • Should every adult take a probiotic? The best evidence supports probiotics for improved lactose digestion and for prevention of difficile infection. Probiotics have also been shown to prevent common illnesses; reduce the duration of gut symptoms; and perhaps even reduce antibiotic consumption.
  • Studies will reveal more about the microbiome and about how probiotics work, for whom and for what indications. As with diet, the answer will most likely not be same for each person.

Prof. Glenn Gibson: Prebiotics and Synbiotics

  • A prebiotic is “a substrate that is selectively utilized by host microorganisms conferring a health benefit”. Researchers can test these substances’ activity in various ways: batch cultures, micro batch cultures, metabolite analysis, molecular microbiology methods, CF gut models, with in vivo (e.g. human) studies being required. Prebiotics appear to have particular utility in elderly populations, and may be helpful in repressing infections, inflammation and allergies. They have also been researched in clinical states such as IBS, IBD, autism and obesity related issues (Gibson et al., 2017).
  • A synbiotic is “a mixture, comprising live microorganisms and substrate(s) selectively utilized by host microorganisms, that confers a health benefit on the host.” While more studies are needed to say precisely which are useful in which situations, synbiotics have shown promise for several aspects of health in adults (Swanson et al. 2020): surgical infections and complications, metabolic disorders (including T2DM and glycaemia), irritable bowel syndrome, Helicobacter pylori infection and atopic dermatitis.

Prof. Hania Szajewska, MD: Biotics for pediatric use

  • Beneficial effects of ‘biotics’ are possible in pediatrics, but each ‘biotic’ needs to be evaluated separately. High-quality research is essential.
  • It is important that we view the use of ‘biotics’ in the context of other things in a child’s life and other interventions.
  • Breast milk is the best option for feeding infants
  • If breastfeeding is not an option, infant formulae supplemented with probiotics and/or prebiotics and/or postbiotics are available on the market.
  • Pro-/pre-/synbiotic supplemented formulae evaluated so far seem safe with some favorable clinical effects possible, but the evidence is not robust enough overall to be able to recommend routine use of these formulae.
  • Evidence is convincing on probiotics for prevention of necrotizing enterocolitis in preterm infants.
  • Medical societies differ in their recommendations for probiotics to treat acute gastroenteritis in children – they appear beneficial but not essential.
  • Synbiotics are less studied, but early evidence indicates they may be useful for preventing sepsis in infants and preventing / treating allergy and atopic dermatitis in children.

Prof. Gabriel Vinderola: Postbiotics

  • The concept of non-viable microbes exerting a health benefit has been around for a while, but different terms were used for these ingredients. Creating a scientific consensus definition will improve communication with health professionals, industry, regulators, and the general public. It will allow clear criteria for what qualifies as a postbiotic, and allow better tracking of scientific papers for future systematic reviews and meta-analyses.
  • The ISAPP consensus definition (in press) of a postbiotic is: “A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”.
  • Postbiotics are stable, so no cold-chain is needed to deliver them to the consumer. Safety is of less concern because the microbes are not alive and thus cannot cause bacteraemia.
  • Research in the coming years will reveal more about postbiotics and the ways in which they can promote human health.

See here for the entire presentation on Biotics for Health.

Probiotics and fermented foods, by Dr. Mary Ellen Sanders (@1:15)

Postbiotics, by Prof. Gabriel Vinderola (@18:22)

Prebiotics and synbiotics, by Prof. Glenn Gibson (@33:24)

‘Biotics’ for pediatric use, by Prof. Hania Szajewska (@47:55 )

Probiotics: How do I know what to prescribe for adult health? by Prof. Dan Merenstein (@1:04:51)

Q&A (@1:20:00)

 

Probiotics in fridge

Designing Probiotic Clinical Trials: What Placebo Should I Use?

By Daniel J. Merenstein, MD, Professor, Department of Family Medicine and Director of Research Programs, Georgetown University Medical Center, Washington DC

Specifying a placebo is one of the most important decisions for a clinical trialist. The first trial I led was a study giving Benadryl to kids to see if it helped them sleep. We spent hours working with our pharmacist on the placebo to make sure it had the same sweet cherry taste of the active drug, Benadryl. We didn’t want parents to be able to determine whether they were randomized to Benadryl or the placebo by comparing the study product to what they had at home. Do study subjects really do this? Yes. Early in my career I was helping an orthopedist who was putting pain pumps directly into a patient’s ankle post-surgery in order to see if it would decrease oral narcotic usage. One of our first patients pulled his pump out, tasted the medicine and called us late at night complaining he was in the saline (placebo) group.

When undertaking a study on probiotics, and specifically probiotic yogurts, we can debate for weeks about the best placebo. Our intervention is yogurt fortified with an additional probiotic. Therefore, our intervention yogurt contains both the starter lactic acid bacteria and the probiotic. So assuming we want both groups to get nutritionally equivalent yogurt that can be blinded our placebo options could be as follows. Note that in recent years, we have become more cognizant that dead microbes may not be biologically inactive.

Placebo Microbiological content of Placebo Research question addressed
Yogurt Live starter cultures, no probiotic What is the contribution of probiotics to any health benefit?
Acidified yogurt No live or dead microbes What is the contribution of live probiotic + live starter cultures to any health benefit?
Heat treated yogurt No live microbes, dead starter microbes Beyond any contribution of dead starter cultures, what is the contribution of live probiotic + live starter cultures to the health benefit?
Heat treated probiotic yogurt No live microbes, dead starter + dead probiotic microbes Beyond any contribution of dead probiotics + dead starter cultures, what is the contribution of live probiotic + live starter cultures to the health benefit?
Probiotic yogurt using a different probiotic Live starter cultures, live probiotic different from the probiotic in the intervention What is the contribution of the intervention probiotic to any health benefit compared to the control probiotic?

 

We chose regular yogurt (the first option above) and now about eight papers later, I would say that about 50% of reviewers question our choice.

There are many reasons the placebo needs to be well considered, including the specific research question under consideration. But an important one is clinical equipoise, “a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial”, as defined Freedman 1987. Thus, for example in a study of a new hypertension drug, one cannot use a placebo that has no chance of lowering a patient’s blood pressure as a comparator as that is ethically indefensible. Instead, a well proven hypertension drug will be studied versus the new experimental drug.

For most of my career the goal in my studies was to pick a placebo that was as inactive as possible that still smelled, looked and tasted like my active intervention. However, the times are changing. When I started working there were fewer than 200 randomized controlled clinical probiotic trials retrievable from PubMed; today the number is over 2,300. Well that means we have gone beyond merely recognizing the value of probiotics in different indications, to detailed comparisons of different probiotic and non-probiotic interventions, so one has to consider how inactive their placebo is for probiotic intervention trials.

In 2020 the American Gastrointestinal Association came out with recommendations and guidelines after they conducted a thorough review of probiotic evidence. (See ISAPP blog ISAPP take-home points from American Gastroenterological Association guidelines on probiotic use for gastrointestinal disorders.) For three indications, they recommended using select probiotics over no or other probiotics, in populations of preterm low birthweight infants, patients receiving antibiotics, and patients with pouchitis. So what does this mean for trials evaluating one of these indications? It means that the placebo should be an active control, a probiotic versus probiotic trial.

Today if I’m asked what placebo should be used, my first question is what indication are you studying? If you are studying infant colic or preterm low birthweight infants, I think you need an active control, such as another probiotic. (Colleagues and I suggested this for probiotic studies on necrotizing enterocolitis in 2013.) If you are studying anxiety, then an inert placebo makes the most sense since insufficient evidence exists for any probiotic for this endpoint as yet. In the case of antibiotic associated diarrhea, it will be a much longer discussion as the data are not clear, but it would be reasonable for an IRB to argue that your placebo should be another probiotic. It is not ethical to deny a placebo group an effective intervention if one is available.

So in the last 15 years of my career the answer to what placebo should I use has greatly changed. As probiotic research has advanced, so has the evidence base for usage. As we proceed with research we now need to consider conducting our clinical trials differently. This is just another example of how probiotic evidence has matured over a relatively short period of time.

ISAPP board members look back in time to respond to Benjamin Franklin’s suggestion on how to improve “natural discharges of wind from our bodies”

Benjamin Franklin, born in 1706, was a multi-talented politician and scientist best known for his discoveries related to electricity. Historians say he was scientifically pragmatic—aiming not just to advance theories, but to solve the most vexing problems of the day.

In 1780, when Franklin read about the intellectual contests being held by The Royal Academy of Brussels (today known as the Royal Flemish Academy of Belgium for Science and the Arts – KVAB), he took it upon himself to write an amusing letter that contained a suggestion for an important scientific challenge: “To discover some Drug wholesome & not disagreable, to be mix’d with our common Food, or Sauces, that shall render the natural Discharges of Wind from our Bodies, not only inoffensive, but agreable as Perfumes.”

Over two centuries later, the organization was prompted for a reply. Writer Brian Van Hooker wrote to the KVAB: ‘I am a writer at MEL Magazine and I am working on a piece about a letter that Benjamin Franklin sent to your organization’s predecessor, the Royal Academy of Brussels, 240 years ago. The letter was entitled “Fart Proudly,” and I’m reaching out to see if anyone at your organization might like to issue a reply to Mr. Franklin’s letter’.

Since ISAPP board member Prof. Sarah Lebeer (University of Antwerp, Belgium) is a KVAB Belgian Young Academy alumna with microbiome knowledge, Bert Seghers from the Academy asked her to help draft a reply. However, since the gut microbiome is not her main area of expertise, she consulted her fellow ISAPP board members. For example, Bob Hutkins, author of a popular ISAPP blog post on intestinal gas, immediately sent her a paper entitled Identification of gases responsible for the odour of human flatus and evaluation of a device purported to reduce this odour with the comment: “The next time a graduate student complains about their project, refer them to this paper and the 5th paragraph of the methods”—a paragraph that describes how scientists in the experiment were tasked with rating the odor of flatus and differentiating between the different smells of sulphur-containing gases.

But it was the answer of Prof. Glenn Gibson (University of Reading, UK) that was incorporated into the ‘formal’ reply to Franklin’s suggestion. “Your suggested topic on improving flatulence odour is amusing, but indeed also very relevant. An outstanding answer to the contest as you formulate it would be ground-breaking,” wrote Profs. Lebeer and Gibson. They noted that gases in the intestine are mainly released by the bacteria living there—but especially the sulphate reducing bacteria contribute to the “traditional” smell due to their production of noxious H2S —and that advances in probiotic and prebiotic science could one day lead to reduced (and “nicer smelling”) gas production by switching hydrogen gas production to methane or even acetate and away from H2S.

Brian Van Hooker summarized: “In other words, Mr. Franklin, they’re working on it and, perhaps sometime within the next 240 years, your dream of non-smelly farts might just come true.”

The KVAB response to Benjamin Franklin concluded: “Your letter is a ripple through time. It may not surprise you that scientific questions can have effects across decades and even centuries. This idea remains the tacit hope of many scientists working together for the progress of humanity. We have not yet invented a reverse time machine, but we send our answer along with your question forward in time, hoping that it may inspire future scientists as your question inspired us.”

Read the MEL Magazine article here.

Read more about gut microbiota & intestinal gas here.

New Spanish-language e-book about fermented foods now available for download

By Dr. 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

Fermented foods and beverages such as yogurt, wine, beer, kefir, kombucha, kimchi, and miso are created with the help of microbes. After more than 10,000 years of practice around the globe, fermentation has finally caught massive attention from a general public interested in knowing more about the fascinating, invisible world of microbes. In essence, the act of fermentation places food in a unique place between raw and cooked. The flavours, tastes, textures and potential health benefits of fermented foods, made possible through the presence of viable or non-viable microbes and their metabolites, are achieved through this set of ancestral food processing techniques. Today’s science allows us to see the functions of fermentation microbes that can make certain nutrients more bioavailable in foods. Fermentation can also reduce certain anti-nutrients and generate a large number of potentially beneficial microorganisms.

To help people learn about fermented foods, I was pleased to collaborate on an e-book with Ricardo Weill, an Argentinian dairy industry expert who first introduced Lactobacillus rhamnosus GG in Argentinian fermented milks in the 1990s, and Alejandro Ferrari, a biologist and scientific communications expert. The book is titled ‘Fermented Foods: microbiology, nutrition, health and culture’, and is currently available only in Spanish.

The book aimed to reach the general public, with scientific concepts but in easy-to-follow language for people with little or no previous knowledge of microbiology, nutrition or food technology. It tells the stories of many types of fermented foods around the world and adds a scientific perspective on their health benefits. The book brings together information from 38 authors from Argentina, Colombia, Japan, Spain and Finland, including ISAPP President Prof. Seppo Salminen, and Martin Russo, a professional chef in Argentina who specializes in fermentation. The book includes the following sections:

Fermentation: An anthropological view

Variety of fermented foods in Japan and other East Asian countries, and the microorganisms involved in their fermentation

Introduction to the intestinal microbiota: its role in health and the disease

Consumption of probiotic fermented milk and its impact on the immune system

Fermented milks, yogurts and probiotics

Kefir and artisanal fermented foods

Fermented meat sausages: Contribution of lactic bacteria in global quality

Lactic fermentation of cereals and Andean ancestral grains

Fermented vegetables and legumes

Fermentation of fruit drinks and drinks

Yeasts in beer and baked goods

Role of fermented foods in diet

Role of lactic acid in the beneficial effects of fermented foods

Microbiological safety of fermented foods

Fermented foods and chronic non-communicable diseases: A narrative review of the literature

Fermentation and gastronomy: A cook among scientists, a scientist among cooks

This e-book initiative started in October 2019, when a symposium about fermented food was organized by the Danone Institute of the Southern Cone (DISC).

The Danone Institute of the Southern Cone (DISC) was founded in 2008, and it is the local chapter for Argentina, Chile and Uruguay of the Danone Institute International network, which gathers 14 Danone Institutes (13 local Institutes and 1 International) in 15 countries. All Danone Institutes are non-profit organizations, dedicated to non-commercial activities and promotion of science.

Since its foundation, the DISC has collaborated with more than 200 experts taking part in different projects, and has served as a collaborative meeting place to reflect with their peers—all of them remarkable scientists coming from different and complementary specialties, focusing on key aspects of public health linked to food.

See the link to our book here:

Fermented Food: Microbiology, Nutrition, Health & Culture. (2020)

See the ISAPP press release about this book in English and en español.

Some previously-produced nutrition books that are freely available in Spanish on the DISC website are:

  • Impact of Growth and Early Development on the Population’s Health and Wellbeing. Perspectives and Reflections from the Southern Cone. (2009)
  • Healthy Growth. Between Malnutrition and Obesity in the Southern Cone. (2011)
  • The Role of Calcium and Vitamin D in Bone Health and Beyond. Perspective from the Southern Cone. (2013)
  • Methodologies Employed in Food Evaluation. An Ibero-American Vision. (2015)
  • Their Impact in Nutrition and Health. A Vision from the Southern Cone. (2018)

Current status of research on probiotic and prebiotic mechanisms of action

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

Human intervention studies in the fields of probiotics and prebiotics assess the health effects of these ingredients, whether it’s improving specific symptoms or preventing the occurrence of a health condition. Yet scientists in the field recognize the importance of learning the ‘chain of events’ by which probiotics and prebiotics are able to confer health benefits. Such mechanistic insights allow better probiotic selection and development of therapeutic approaches, as well as more precise dosing.

Mechanisms of action for probiotics and prebiotics are complex and often difficult to pinpoint, especially since any given health benefit may derive from multiple co-functioning mechanisms. However, scientists have made incremental gains in understanding these mechanisms. This scientific progress was covered in a recent webinar co-presented by ISAPP and ILSI-Europe, titled Understanding Prebiotic and Probiotic Mechanisms that Drive Health Benefits. Speakers for the webinar were:

  • Sarah Lebeer, University of Antwerp, Belgium
  • Colin Hill, University College Cork, Ireland
  • Karen Scott, University of Aberdeen, UK
  • Koen Venema, Maastricht University – campus Venlo, The Netherlands

The webinar was held live on September 17, 2020. Of the 499 webinar registrants, 357 attended the webinar live from 57 countries, from Australia to the US. ISAPP and ILSI-Europe hope the webinar will serve as a resource for people who want a rapid overview about mechanisms of action.

Watch the full webinar here, and read further for a summary of key points from these experts.

Prebiotic benefits and mechanisms of action

Prebiotics are defined as substrates that are “selectively utilized by host microorganisms conferring a health benefit”. ‘Utilization’ in the gut may involve crossfeeding, which means products produced by the first microbes degrading the prebiotic can then be used by different members of the host microbiota – so it may take a series of complex steps to get to a final health outcome. However, selective utilization and health benefit are always required for a substance to meet the definition of a prebiotic.

The health benefit of a prebiotic can be local (in the gut) or systemic. Locally, prebiotics can act via fecal bulking, as they are typically types of fiber. In addition, they can produce short-chain fatty acids (SCFAs), which reduce gut pH and thereby can discourage pathogenic and toxigenic activity of gut microbes, increase calcium ion absorption and provide energy for gut epithelial cells.

Systemic functions of prebiotic metabolism include them being used as substrates for microbes that produce or interact with host cells to produce molecules with neurochemical, metabolic or immune activity. Further, SCFAs can end up in the blood and can reach the liver, muscles and the brain. The SCFAs interact with specific host receptors and can lead to the release of satiety hormones or interact with receptors in the liver, adipose tissue and muscle tissue, leading to reduced inflammation. Prebiotics can also interact directly with immune cells.

Probiotic health effects and mechanisms of action

Health and disease are the end results of complex interactions on a molecular scale within a human or animal host.  Host molecules also interact with microbial molecules, including those molecules introduced with or produced by probiotics. Designing studies to discover probiotic mechanisms in human research is extremely challenging because both host and probiotic are very complex systems that most probably engage with one another on multiple levels. Probiotic molecules can have direct effects and downstream effects, and we are aware of only a few cases where a health effect can be tied to one specific probiotic molecule.

Probiotics can interact directly with the host, but also can act indirectly by influencing the microbiome. There may be many different mechanisms by which a given probiotic interacts with the host.

It is interesting to note that probiotics use some of the same types of mechanisms (pili, small molecule production, etc.) that are used by pathogens, microbes that have a detrimental effect on the host.  But these shared mechanisms are usually connected to surviving or colonising strategies, not those that cause damage to the host.

L. rhamnosus GG is a well-researched model probiotic, for which many mechanisms have been identified, including pili, immune modulators and lactic acid production, some mechanisms shared with other probiotic strains and species. Other studies have identified mechanisms for novel types of probiotics. For example, in mice and humans taking a strain of Akkermansia, heat killed cells had the same or even better effect on markers of metabolic health, which implies that the molecules (perhaps proteins in the bacteria, unaffected by heat treatment) are mediating the effect in this case.

See here to watch the webinar in full.

 

 

60 Minutes’ 13 minutes on probiotics

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer 

On June 28, 60 Minutes aired a 13-minute segment about probiotics titled, “Do Probiotics Actually Do Anything?” Unfortunately the media segment did not provide listeners with a nuanced perspective.

‘Probiotics’ were treated as if they were one entity, ignoring the best approach to addressing the topic of what probiotics do: evaluate the evidence for specific strains, doses and endpoints, and then make a conclusion based on the totality of the evidence. They would have found that many experts agree that actionable evidence exists for certain probiotics to prevent antibiotic associated diarrhea (here, here), prevent upper respiratory tract infections (here), prevent morbidity and mortality associated with necrotizing enterocolitis (here,), treat colic (here), and treat acute pediatric gastroenteritis (here). (For an overall view of evidence, see here.)

Importantly, not all retail probiotics have evidence (at least evidence that is readily retrievable, see here and here). But that does not mean that none do.

The 60 Minutes segment also highlighted questions about probiotic safety. No intervention is without risk, and no one claims as much for probiotics. Prof. Dan Merenstein, MD, just one clinical investigator of probiotics, has collected over 20,000 pediatric clinical patient days’ worth of safety data over the past eight years of clinical investigation, with no indication of safety concerns. In fact, participants in the placebo group generally have more adverse events than in the probiotic groups. But importantly, the safety standard for probiotics was mischaracterized by 60 Minutes. According to Dr. James Heimbach, a food safety expert (not interviewed in the segment) who has conducted 41 GRAS determinations on probiotics, over 25 of them notified to the FDA, he objects to the statement that GRAS is a lower safety bar than a drug. He clarifies:

“The safety standard that applies to food additives and GRAS substances, “reasonable certainty of no harm,” is a far higher standard than that applying to drugs. Drugs are judged against a risk/benefit standard, which can potentially allow quite dangerous drugs on the market provided they offer a significant benefit. The safety standard for drugs also applies only to prescribed doses for specific individuals over prescribed durations. The food-additive/GRAS substance standard, on the other hand, requires safety at any biologically plausible level of intake, for any person (child, adult, elderly; pregnant; etc.), over a lifetime. And it is a risk-only standard—no potential benefit is allowed to override the “reasonable certainty of no harm” standard. Additionally, in the case of GRAS substances (which includes most probiotics), the evidence of safety must be published in the peer-reviewed scientific literature and be widely accepted by the scientific community as well as by government regulators.”

Finally, the story implied that benefits people claim for themselves when using probiotics are due to a placebo effect. This ignores the many properly controlled studies directly comparing the effects of specific probiotics to placebos. A positive trial on probiotics, such as observed in this recent trial on irritable bowel syndrome symptoms (here) and in most trials included in Cochrane meta-analyses on prevention of C. difficile-associated diarrhea (here), means that positive effects were observed beyond any placebo effect. The placebo effect is real, equally applicable to probiotics and drugs, but as with all clinically evaluated substances, properly controlled trials control for this effect.

The probiotic field has come a long way over the past 20 years with regard to number and quality of clinical trials. In that time, well-done systematic reviews of the evidence have found benefits for specific probiotics for specific conditions, while also finding a lack of evidence for beneficial effects in other contexts. There are of course well-conducted clinical trials that have failed to demonstrate benefit (here, here, here). This should not be equated to mean that probiotics do not do anything.

Many challenges remain for improving the quality of the evidence across the wide range of different strains, doses, endpoints and populations. More clinical research needs to be conducted in a manner that minimizes bias and is reported according to established standards. Confidence in the quality of commercial products could be improved by industry adopting third party verification (here), and the quality of products targeting compromised populations need to be fit for purpose (here). Companies should stop using the term ‘probiotic’ on products that have no evidence warranting that description. We need to understand much better how a person’s individual situation, such as diet, microbiome, use of medications and fitness, impact the ability of a probiotic to promote health. Much remains to be learned in this evolving and exciting field. As Dr. Merenstein says, “The key question is not, ‘Do probiotics actually do anything?’, as that is easily answered ‘yes’ when you look at robust placebo-controlled trials of specific probiotics. Better questions are ‘Which probiotics do anything, and for what?’”

Further reading:

Misleading press about probiotics: ISAPP responses

ISAPP take-home points from American Gastroenterological Association guidelines on probiotic use for gastrointestinal disorders

New publication gives a rundown on probiotics for primary care physicians

Safety and efficacy of probiotics: Perspectives on JAMA viewpoint

ISAPP welcomes three new board members

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

ISAPP is pleased to announce that Profs. Kelly Swanson PhD, Daniel Tancredi PhD, and Gabriel Vinderola PhD have joined the ISAPP board of directors. The expertise of these three globally recognized academic experts complements that of the current board members, together comprising a leading global group of distinguished scientific and clinical experts in the fields of probiotics, prebiotics, synbiotics, fermented foods, and postbiotics.

Read more about ISAPP’s newest board members:

Kelly Swanson is the Kraft Heinz Company Endowed Professor in Human Nutrition, a professor in the Department of Animal Sciences and Division of Nutritional Sciences and an adjunct professor in the Department of Veterinary Clinical Medicine at the University of Illinois at Urbana-Champaign. He is an expert in the field of fiber and prebiotics, and brings to ISAPP knowledge of application of these substances to companion and agricultural animals. Kelly, who trained with previous ISAPP Board member, George Fahey, is considered one of the top authorities in animal gut health, microbiome, and nutrition. His research has focused on testing the effects of nutritional intervention on health outcomes, identifying mechanisms by which nutrients impact gastrointestinal microbiota, host gene expression, and host physiology. Kelly served on the prebiotic consensus panel (here), led the ISAPP synbiotics consensus panel, and is lead author on the synbiotics outcome paper, currently in press with Nature Reviews Gastroenterology and Hepatology.

Dan Tancredi is a biostatistician with an appointment as an Associate Professor (full professor starting July 1, 2020) in Residence at UC Davis Department of Pediatrics, and is also with the Center for Healthcare Policy and Research. Dan works extensively on NIH-sponsored research and as an NIH scientific reviewer. He has an extensive record of collaboration with ISAPP; he has served as an invited expert and/or speaker at all but one ISAPP meeting since 2009, providing his perspectives on how to improve the quality and scientific impact of probiotic trials and how to conduct systematic reviews that rigorously and transparently synthesize the evidence from these trials. He has been a co-author on 6 ISAPP papers (here, here, here, here, here, here and here), including a 2020 paper “Probiotics as a Tx Resource in Primary Care” published in the Journal of Family Practice (see New publication gives a rundown on probiotics for primary care physicians). Dan was invited to author the Nature commentary on the landmark probiotics trial by Panigrahi, et al. for reducing newborn sepsis in the developing world—showing his reputation as a trusted voice for assessing the quality of probiotic research.

Gabriel Vinderola is a professor at National University of Litoral, Santa Fe, Argentina and Principal Researcher at CONICET, at the Dairy Products Institute (UNLCONICET). He is an expert in lactic acid bacteria, fermented foods, and probiotics. Gabriel has forged academic collaborations with academic and industrial scientists in numerous countries in Europe and with industrial colleagues in Argentina. He has been active in several countries in South America working with regulators to assure that their actions on probiotic guidelines are science-based, including his recent efforts consulting on guidelines for probiotics for the Codex Alimentarius. He has written blogs for ISAPP, translated ISAPP videos and infographics into Spanish, and was an expert on the ISAPP consensus panel on postbiotics. His research has focused on technological aspects of probiotics (biomass production, dehydration, storage, food matrices) and fermented foods. He is an active public science communicator in Argentina on the topics of probiotics, prebiotics, fermented foods, and the microbiome. See Growing interest in beneficial microbes and fermented foods in Argentina for some examples. Gabriel represents the first ISAPP board member from South America and we anticipate his involvement will help ISAPP expand its presence and connections in Latin America.

 

ISAPP partners with British Nutrition Foundation for fermented foods webinar

Did you miss the live webinar? Access the archived version here. Read the speaker Q&A here.

From sourdough starter tips to kombucha flavor combinations – if you’ve checked a social media feed lately, you’ll know how many people are sharing an interest in fermented foods as they self-isolate during the pandemic. And with this rise in popularity comes a host of questions about the practice and the science of fermented foods.

To meet the need for science-based information about fermented foods, ISAPP has partnered with the British Nutrition Foundation (BNF) on a free webinar titled ‘Fermented Food – Separating Hype from Facts.’ The BNF is a UK-based registered charity that brings evidence-based information on food and nutrition to all sectors, from academia to medicine.

The webinar, designed for practicing dietitians and nutrition-savvy members of the public, featured three leading scientific experts who explained the microbiology of fermented foods, the evidence for their health effects, and who might benefit from making these foods a regular part of the diet. Viewers will come away with a clear understanding of what fermented foods are and what evidence exists for their health benefits.

The webinar was held live on Wednesday, July 1, 2020 from 1pm-2pm (BST).

Webinar speakers & topics

 Understanding fermented foods: Dr. Robert Hutkins, University of Nebraska, USA

Exploring the evidence for effects of fermented foods on gastrointestinal health – how strong is it? Dr. Eirini Dimidi, Kings College London

What role can fermented foods have in our diet? A public health perspective, Anne de la Hunty, British Nutrition Foundation

For a quick primer on fermented foods, see the short ISAPP video here or the ISAPP infographic here.