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.
Popular media, misinformation and ‘biotics’
/in News /by KCBy Mary Ellen Sanders, PhD, Executive Science Officer, ISAPP
Encountering misinformation is all too easy when seeking understanding of probiotics, prebiotics, synbiotics, and postbiotics (collectively, ‘biotics’). It can be perpetuated both by proponents and detractors. Through this lens, I’m prompted to comment on some high profile pieces making news recently. A Washington Post article Probiotic supplements may do the opposite of boosting your gut health was published on March 28, 2023, by Anahad O’Connor. This author was then interviewed for a CBS video story Studies find that probiotics can harm gut health on March 30, 2023. Then, a National Geographic article Probiotics, prebiotics, postbiotics. What’s the difference? was published on the same day.
These pieces appropriately acknowledge the availability of evidence linking probiotics to human benefits. Yet the points raised about potential harms from probiotics and a misunderstanding of what ‘biotic’ substances really are deserve comment.
Harms of probiotics
Amid a backdrop of marketing and media messaging lauding the many benefits of probiotics, reporters are understandably drawn to the counter message that ‘probiotics can harm gut health’. Safety must always be rigorously assessed, as encouraged by a 2023 ISAPP paper focused on emerging issues in probiotic safety (see here). However, the claims of harm made – although generated from studies in humans – are not based on clinical endpoints. Instead they are based on either microbiome endpoints (Suez et al. 2018) or on post hoc analysis of biomarker outcomes (Wastyk et al. 2023). The limitations of the Suez et al. 2018 study were discussed in more detail previously (See: Clinical evidence and not microbiota outcomes drive value of probiotics). This paper evaluated the effect of one multi-strain probiotic product and is the only paper I am aware of that shows that probiotics inhibit microbiome recovery after antibiotic treatment. The paucity of supporting evidence for the harm supposedly documented in this paper is not mentioned in the stories. It is noteworthy that in the Wastyk et al. 2023 paper the authors acknowledge that the study did not achieve its primary objectives, and in referring to their post hoc analysis (including the ‘evidence’ for harm), they specifically acknowledge that such analysis is not conclusive evidence: “We next leveraged aspects of our study design … in a discovery analysis process to reveal trends that could inform possible … hypotheses for future studies.” These studies are best used for generating hypotheses requiring further study.
Another criticism that was leveraged as evidence that probiotics cause harm is that probiotics reduce microbiota diversity. Any probiotic-induced reduction in diversity of fecal microbiota has not been shown to be associated with harm. Further, most studies show no significant overall changes in microbiome composition in response to traditional probiotic administration. However, it should be understood that the value of diversity as a marker of health remains unproven. The evidence is from observational studies and only shows associations, not causality.
As stated, relying on microbiota endpoints to advance the idea that probiotics cause harm is not justified. But I cannot escape the fact that probiotic proponents in part contribute to this thinking. When probiotics are marketed as being able to ‘balance the microbiota’, without clinical data to substantiate a benefit, aren’t they promoting the same limited science?
Adherence to definitions of biotics needed
ISAPP has rigorously considered and offered definitions for probiotics, prebiotics, synbiotics, postbiotics and fermented foods (see here for a summary), which have been presented in highly cited reviews in Nature Reviews Gastroenterology and Hepatology (see here, here, here, here and here). These efforts were undertaken to advance a common understanding of these terms, so that precision can be attained in communications on them.
This objective has been far from realized. Misuse of these terms continues on product labels, in scientific publications, and in popular press communications.
The articles cited above compelled me to offer some take home messages for those responsible for accurately communicating science:
Probiotics are: Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host
Prebiotic is: A substrate that is selectively utilized by host microorganisms conferring a health benefit on the host
Postbiotic is: Preparation of inanimate microorganisms and/or their components that confers a health benefit on the host
Conclusion
Both the positive and negative effects of probiotics based on microbiome assembly can be misrepresented in the press, by some marketing claims, and sometimes in scientific literature. The field will benefit from communications that acknowledge the limitations of available science. Further, it’s important for clarity in communication that the field coalesces around established definitions and honor the criteria needed to meet those definitions. Additionally, scientists and medical professionals should apply the same scrutiny and critical thinking to fermented foods as they do to probiotics.
ISAPP encourages healthy debate, critical review of new studies and innovative research. Since ISAPP’s mission is focused on promoting the science of these substances, journalists are invited to reach out as needed to ISAPP for an evidence-based perspective on this evolving field (www.ISAPPscience.org).
Episode 20: How to navigate probiotic evidence and guidelines for pediatric populations
/in Podcast, Season Two /by LauraPodcast: Play in new window | Download
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The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
How to navigate probiotic evidence and guidelines for pediatric populations, with Dr. Hania Szajewska
Episode summary:
In this episode, the ISAPP podcast hosts talk about evidence and guidelines for probiotics in pediatric populations, with Prof. Hania Szajewska MD PhD, of the Department of Paediatrics at the Medical University of Warsaw, Poland. They talk about some of the inconsistencies between different medical organizations’ guidelines for pediatric probiotic use, and how clinicians can move forward with recommendations based on the best available evidence.
Key topics from this episode:
Episode abbreviations and links:
About Prof. Hania Szajewska:
Hania Szajewska, MD, is Professor and Chair of the Department of Paediatrics at the Medical University of Warsaw and the Chair of the Medical Sciences Council. Among her various functions, she served as the Editor-in-Chief of the Journal of Pediatric Gastroenterology and Nutrition; a member of the Council and then as the General Secretary of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN); the Secretary of the ESPGHAN Committee on Nutrition. Most recently, she joined the Board of Directors of the International Scientific Association for Probiotics and Prebiotics (ISAPP). Prof. Szajewska has broad interests in pediatric nutrition but her research focuses on the effects of early nutritional interventions on later outcome; and the gut microbiota modifications such as with various biotics (probiotics, prebiotics, synbiotics, postbiotics). She is or has been actively involved in several European Union-funded research projects. She is an enthusiastic advocate for the practice of evidence-based medicine. Prof. Szajewska has co-authored more than 400 peer-reviewed publications and 30 book chapters. Citations >18,141. Hirsch index 72 (WoS, March 2023).
Episode 19: Questioning the existence of a fetal microbiome
/in Podcast, Season Two /by LauraPodcast: Play in new window | Download
Subscribe: Apple Podcasts | Spotify | RSS
The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
Questioning the existence of a fetal microbiome, with Dr. Kate Kennedy
Episode summary:
In this episode, the ISAPP podcast hosts tackle the debate on the existence of a fetal microbiome, with guest Kate Kennedy PhD of McMaster University in Canada. They talk about Kennedy’s recent co-first-authored paper in Nature, which concludes that it is not biologically plausible that the fetus harbors live microorganisms, and that previous microbial sequencing studies on the fetal microbiome did not account for the many sources of contamination.
Key topics from this episode:
Episode abbreviations and links:
About Dr. Kate Kennedy:
Kate completed her PhD on the role of the maternal gut microbiome in perinatal programming in the lab of Dr. Deborah Sloboda at McMaster University. She previously completed her BSc and MSc in Biology at the University of Waterloo. Her research explores host-microbiome relationships in pregnancy, early-life, and aging to understand their role in modulating health and disease risk.
Are the microbes in fermented foods safe? A microbiologist helps demystify live microbes in foods for consumers
/in Consumer Blog, ISAPP Science Blog /by KCBy 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 the Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina.
Since very early in my career I was drawn to science communication. I feel that rather than just producing my own results, silently in my lab, I can extend the reach of the science by amplifying other people’s work. At least in the southern cone where budgets for research have been always limited, science communication is a way to be active in science.
Before the pandemic I used my Instagram account mostly to share personal moments with my circle of family and friends. But when the COVID-19 pandemic hit, I saw interest in fermented foods skyrocket. I started sharing tips about how to prepare fermented foods, telling the science behind them, separating myths from facts, making Instagram Live videos with fermentationists, nutritionists, pediatricians and gastroenterologists, and I turned my personal Instagram account into a public one with an outreach of more than 100,000 followers (@gvinde), from Mexico down to Argentina.
During the pandemic, people were largely homebound and concerned about staying healthy. The idea of healthy food to keep a diverse gut microbiome that had the potential to enhance our gut and respiratory immune systems against coronavirus really resonated with people. I even had the chance to participate in several radio and TV programs discussing these topics as well as making yoghurt, kefir, kombucha, sauerkraut and sourdough bread at home. I saw that people had the time to devote part of their days at home to keep these communities of microbes “cooking” for them. But these activities revealed to me that more people than I realized did not know that we can eat microbes in a safe way and that they may actually be good for us.
In my encounters, I found much confusion about fermented dairy products. People believe that dairy products must be kept refrigerated, but at the same time they see ultrapasteurized milk, powdered milk or hard cheeses marketed at room temperature. People find it difficult to understand why pasteurized milk should go in the refrigerator but not unopened ultrapasteurized milk.
Some hesitancy around bacterial safety exists because Argentina leads the world in annual cases of Uremic Hemolitic Syndrome (UHS), a life-threatening condition for children, especially those under the age of 5 years, caused by shiga-toxin producing Escherichia coli. Almost 400 children get sick in Argentina every year due to UHS. Among other recommendations, pediatricians tell parents not to offer their children unpasteurized dairy products. This leads to the the most common question I receive on Instagram from parents worried about yoghurt safety: Is yoghurt pasteurized? “No!” I emphasize. “Yoghurt is not pasteurized, but it is made out of pasteurized milk. In fact, yoghurt has viable bacteria.” And this is when the panic begins.
“If yoghurt has live bacteria, then can’t any bacteria grow there, even the bacteria responsible for UHS? If I leave yoghurt outside the refrigerator or in my car too long, won’t this make it more likely that the UHS bacteria will grow?” This is where I try to use an army of arguments to communicate science in the simplest possible way, from more philosophical to more science-based facts.
The first thing I share is that fermentation was invented well before refrigerators. Fermentation was used by people to preserve foods, for periods well longer than the time it takes to take the yoghurt from the supermarket to make it home or than the time a yoghurt sits in the backpack of my child waiting for school lunchtime. I once posted that I ate a yoghurt that was left in my car for one whole day. That generated a lot of debate on social media!
Then I inform them that the fermentation process to make yoghurt causes the pH to drop well below values needed for pathogens to grow. That it is highly unlikely that a pathogen can enter a well-sealed yoghurt, and in the event that it would be possible, the acidic conditions would impair the pathogen from growing to a level that could be life-threating.
People not only worried about yoghurts bought in the supermarket, well-sealed and made under the strictest safety conditions in industry. In the pandemic many parents learned how to make yoghurt at home, and they wanted to know how safe it is. In these cases, I advised the following to assure their homemade yogurt was safe: use a yoghurt from the supermarket to launch your own fermentation, use pasteurized milk, use good quality water to wash your kitchen devices, and wash your hands properly. In addition you can use a domestic pHmeter or pH indicators to make sure pH dropped below 4.5. In a successful fermentation – after about 1 gallon sitting 8-12 hours at a warm temperature – the fluid milk will transform into a gel. If not, you should discard it.
If these arguments are not enough, then I draw their attention to the well-respected product milk kefir. At least in this region, kefir is surrounded by a halo of “something that is good, no matter what”. People are familiar with the process of fermenting milk kefir at room temperature for a full day. So I make this comparison: commercial yoghurt is fermented for 6 hours, then it is refrigerated and taken to the supermarket. If you are OK letting milk kefir ferment for a whole day, shouldn’t yogurt sitting without refrigeration for a few more hours be harmless enough? It likely would only get more acidic because bacteria will resume fermentation. This fermented food would not become a life-threatening food in just a couple of hours. If milk kefir does not in 24 hours, why should yoghurt?
To further argue, I comment that kombucha is fermented at room temperature for 10 days, sauerkraut for 2 weeks and kimchi for several months. And they are all consumed with their microbes alive. They key is that the microbes that flourish make the environment inhospitable to pathogens.
Still I feel that there is a lot of uncertainty among consumers about the safety of fermented foods and this is may be an obstacle to making them more popular. Scientists must meet the challenge to communicate to lay audiences about how to make fermented foods safely at home and how to store them so they are safe. Nothing is ever 100% safe, but the small risks associated with fermented foods are greatly outweighed by the enjoyment of making and consuming fermented foods.
Additional reading:
Suggestions for Making Safe Fermented Foods at Home
2022 TEDx talk
2021 Teaching how to make kefir on TV during the pandemic
2019 participation in Argentina’s most famous TV show, featuring the same host for more than 50 years non-stop
Probiotic Use in Horses: What is the Evidence?
/in ISAPP Science Blog /by KCBy Kelly S. Swanson, PhD, The Kraft Heinz Company Endowed Professor in Human Nutrition, University of Illinois at Urbana-Champaign, USA
Horses play a special role in many people’s lives, serving as a partner in leisure activities, therapy, various forms of work, and athletic competitions. Being large herbivores, they are adapted to a diet rich in grasses and other high-fiber forages. The complex community of microbes inhabiting the hindgut (cecum and colon) is necessary for the efficient breakdown of these fibers as well as maintaining the gastrointestinal health and overall health of horses. In recent years, a lot has been learned about the composition and activity of the gastrointestinal microbiota of horses and their role in health and disease (Kauter et al, 2019). There has also been interest in testing whether yeast- or bacteria-based probiotics may help manage equine health and disease.
Is there evidence supporting probiotic use in horses? The answer depends on the animal’s life stage, dietary and exercise strategy, and health status.
Probiotics for foals
A common target of probiotic use has been young growing foals. Similar to other host species, the gastrointestinal microbiota population of foals has a lower diversity and stability than that of adult horses (Earing et al., 2012; De La Torre et al., 2019). This instability makes foals more susceptible to pathogen-induced microbiota alterations, diarrhea, dehydration, and intestinal inflammation (Frederick et al., 2009; Schoster et al., 2017; Oliver-Espinosa, 2018). But probiotic use in foals has had both helpful and harmful outcomes. Positive results were obtained with a probiotic containing 5 Lactobacillus strains (L. salivarius YIT 0479, L. reuteri YIT 0480, L. crispatus YIT 0481, L. johnsonii YIT 0482, L. equi YIT 0483), which were shown to increase body weight and reduce diarrhea incidence in 3-4 week old foals (Yuyama et al., 2004). Similarly, a probiotic composed of 4 Lactobacillus strains (L. reuteri KK18, L. ruminis KK14, L. equi KK15, L. johnsonii KK21) and 1 Bifidobacterium strain (B. boum HU) was reported to reduce the incidence and duration of diarrhea in foals during their first 5 months of life (Tanabe et al., 2014). However, administration of a different probiotic (L. pentosus WE7) was associated with anorexia, development of diarrhea, and greater need for veterinary examination and treatment (Weese and Rousseau, 2005). Based on the evidence thus far, caution should be used when considering probiotic use in foals.
Probiotics for adult horses
Even though adult horses have a more stable and rich gastrointestinal microbiota than young animals, microbiota disruptions can occur with rapid changes in diet, transportation stress, the onset of gastrointestinal disease, or other diseases such as laminitis or grass sickness (Garrett et al., 2002; Costa et al., 2012; Moreau et al., 2014). Horses are susceptible to gastrointestinal disorders such as enterocolitis that may be due to antibiotic use, stressful conditions, or pathogen infection (e.g., Clostridioides difficile; Salmonella). Not all probiotic interventions have led to improvements, but there are examples of success. In one study, a Saccharomyces boulardii treatment reduced the severity and duration of illness in horses with acute enterocolitis (Desrochers et al., 2005). In another study, a probiotic mixture of 3 Lactobacillus strains (of the species L. plantarum, L. casei, L. acidophilus) and 1 Enterococcus strain (E. faecium) reduced the incidence of Salmonella shedding in horses admitted for routine medical and surgical treatments (Ward et al., 2004). Overall, there is weak evidence for probiotic use in horses with enterocolitis at this time.
In healthy adult horses, the reasons for using probiotics may differ depending on the fiber and starch content of the diet being fed. In horses fed a high-fiber diet composed of grasses and hay, live yeast cultures (Saccharomyces cerevisiae) have increased nutrient breakdown and energy extraction (Medina et al., 2002; Jouany et al., 2008; Garber et al., 2020). Such increased efficiency may be helpful for horses eating low-quality forages or performance animals that have higher energy requirements. To meet the energy needs of many high-energy or performance animals, grains that are rich in starch and have a higher energy content are often fed. A high-starch diet helps meet the energy requirement, but if not managed properly, it can exceed the capabilities of the horse’s small intestine, resulting in significant starch loads entering the hindgut. These starches are highly fermentable by hindgut microbiota, resulting in the rapid production of lactic acid and short-chain fatty acids. The accumulation of these acids can lead to hindgut acidosis and diseases such as colic or laminitis. Lactobacilli have been shown to modify equine microbiota populations, decreasing amylolytic bacteria and increasing lactic-acid utilizers, and ultimately attenuating starch breakdown and pH decline ex vivo (Harlow et al., 2017). Live yeast cultures have also been shown to help attenuate the hindgut lactic acid concentrations and maintain the hindgut pH of horses fed high-starch diets (Medina et al., 2002). These studies suggest that probiotics may be useful in increasing the digestive efficiency and/or maintaining the hindgut homeostasis of healthy adult horses.
Probiotics for horse athletic performance
Because probiotics have been used to support exercise performance in humans (Pyne et al., 2015), similar interventions have been tested in performance horses recently. In one study a probiotic mixture of 5 Lactobacillus strains (L. acidophilus DSM 32241, L. plantarum DSM 32244, L. casei DSM 32243, L. helveticus DSM 32242, L. brevis DSM 27961), 2 Bifidobacterium strains (B. lactis DSM 32246, B. lactis DSM 32247)), and 1 Streptococcus strain (S. thermophilus DSM 32245) reduced post-exercise blood lactate concentrations and modified blood and urinary metabolite profiles (Laghi et al., 2018). In another study, a probiotic mixture of 2 Lactobacillus strains (from the species L. plantarum and L. paracasei) increased blood oxygen saturation and reduced blood lactic acid concentrations (Zavistanaviciute et al., 2019). Because lactic acid production and accumulation results in fatigue and reduced performance, these studies suggest that probiotics may support athletic performance in horses. The results of these studies are promising, but more research is necessary.
State of the science
Data to support use of probiotics in horses is emerging, but the occurrence of harmful outcomes in at least one study reinforces the need for high quality studies that can precisely establish efficacious conditions and formulations for use. Similar to recommendations for other host species, equine probiotics should provide an effective dose, be designed for horses, target a specific life stage and condition, and be supported by evidence. It is important to remember that probiotic efficacy can depend on specific microbial strains, supplement form, storage conditions, and dosage – see ISAPP’s infographic ‘What Qualifies as a Probiotic’ for more details on probiotics.
Kelly Swanson joined the ISAPP board of directors in June, 2020, providing valuable expertise in animal gut health and overall health. Swanson also chaired the 2019 ISAPP-led international consensus panel on the definition of synbiotics.
Episode 18: The definition of postbiotics
/in Podcast, Season Two /by LauraPodcast: Play in new window | Download
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The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
The definition of postbiotics, with Dr. Gabriel Vinderola and Prof. Seppo Salminen
Episode summary:
In this episode, the ISAPP podcast hosts join guests Gabriel Vinderola, PhD, Principal Researcher at the
National Scientific and Technical Research Council (CONICET) and Associate Professor at University of Litoral in Argentina, and Seppo Salminen, PhD, Professor at University of Turku in Finland, to discuss the relatively recent definition of postbiotics and what kinds of substances are included in this category. They talk about the criteria for something to qualify as a postbiotic, common mechanisms of action for postbiotics, and how postbiotic science has brought new perspectives on the study of probiotics.
Key topics from this episode:
Episode abbreviations and links:
Additional Resources:
Postbiotics. ISAPP infographic (also available in Japanese and Spanish).
Behind the publication: Understanding ISAPP’s new scientific consensus definition of postbiotics. ISAPP blog post.
Definition of postbiotics: A panel debate in Amsterdam. ISAPP blog post.
About Dr. Gabriel Vinderola:
Gabriel Vinderola graduated at the Faculty of Chemical Engineering from the National University of Litoral (Santa Fe, Argentina) in 1997. He obtained his Ph.D. in Chemistry in 2002 at the same University. He collaborated with several research teams in Canada, Spain, France, Italy, Germany, Brazil and Finland. He is presently Principal Researcher of the National Scientific and Technical Research Council (CONICET) and Associate Professor at the Food Engineering Department of his home Faculty. He participated in 1999 in the development of the first commercial cheese carrying probiotic bacteria in Latin America. In 2011, he was awarded the prize in Food Technology for young scientists, by the National Academy of Natural, Physic and Exact Sciences from Argentina. He published more than 120 original scientific publications in international refereed journals and book chapters. From 2020 to present, he serves as a member of the board of directors of the International Scientific Association for Probiotics and Prebiotcis (ISAPP). He is engaged in science communication to the general public through Instagram (@gvinde).
About Prof. Seppo Salminen:
Seppo Salminen, MSc, MS, PhD, is a Senior Advisor, Functional Foods Forum (FFF) at the University of Turku. His areas of expertise are gut microbiota, probiotics and prebiotics, nutrition and food safety, and EU regulations. Seppo teaches the topics of lactic acid biotechnology, functional foods and EU legislation and conducts research into food and health, intestinal microbiota, probiotics, prebiotics, functional foods, food legislation, health claims, and novel foods.
Episode 17: Using metabolomics to learn about the activities of gut microbes
/in Podcast, Season Two /by LauraPodcast: Play in new window | Download
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The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
Using metabolomics to learn about the activities of gut microbes, with Dr. Anisha Wijeyesekera
Episode summary:
In this episode, the ISAPP podcast hosts address the topic of metabolomics with Dr. Anisha Wijeyesekera, PhD, a Lecturer in the Department of Food and Nutritional Sciences at the University of Reading, United Kingdom. Dr. Wijeyesekera gives an overview of how metabolic profiling works, including the information provided by different biological samples, and discusses how metabolomics can be used to piece together the contributions of microbes to host health.
Key topics from this episode:
Episode abbreviations and links:
About Dr. Anisha Wijeyesekera:
Anisha is a Lecturer in the Department of Food and Nutritional Sciences at the University of Reading, United Kingdom. She previously worked at Imperial College London, where she also obtained her PhD (in Biochemistry). Anisha’s research applies a combined microbial and metabolic phenotyping approach, to better understand the tripartite relationship between diet, gut microbiota and human health. At the University of Reading, she conducts in vitro and in vivo studies for functional assessment of the gut microbiota, particularly in response to prebiotics and probiotics. The ultimate aim is to use this information to tailor nutritional or other interventional therapy to improve health outcomes.
How metabolites help us to understand the effect of gut microbes on health
/in ISAPP Science Blog /by KCBy Dr. Anisha Wijeyesekera, University of Reading, UK
Much literature relating to the gut microbiota has focused on microbial composition (for example, using culture-dependent and -independent molecular biology approaches). Composition is important; knowing which microbes are present in a community enables us to gain insight into population dynamics and how these may be affected by disease, lifestyle and environmental factors (including diet). However, composition does not provide information on microbial function, and considering the gut contains the most metabolically active microbial community in the whole body, it is thus equally as important to be able to answer the question “what are the microorganisms doing”? This is of particular importance with respect to better understanding the impact of dietary interventions such as prebiotics, probiotics and other ‘biotics on health, where health benefits conferred on the host are mediated via the gut microbiota.
Investigating microbial function
Advances in phenotypic analytical technologies (for example, high-throughput sequencing, biochemical analysis, as well as bioinformatics and other multivariate data analysis approaches), have resulted in a stepwise change in our understanding of microbial function. Metabolic phenotyping (also referred to as metabolomics, metabonomics or metabolic profiling) is an exciting field in systems biology that provides information on the multiple metabolic mechanisms taking place in a system, at a given moment in time (see here). This top-down approach enables high-throughput detection and quantification of low molecular weight molecules present in a biological sample at the time of sampling, without a priori knowledge of metabolites present. Hence, it is ideally suited to augment and complement information obtained from microbial profiling approaches such as metataxonomics, to gain deeper insight into microbial function.
Metabolic phenotyping is conducted by applying analytical chemistry technologies (typically, 1H-nuclear magnetic resonance spectroscopy, and/or mass spectrometry often with chromatographic separation techniques such as gas chromatography and liquid chromatography (for prior separation of molecules followed by detection)) to capture a biochemical snapshot of a sample. In human samples (e.g. urine, blood plasma/serum and stool), metabolites detected using metabolic phenotyping are low molecular weight molecules and include intermediate and end by-products of endogenous host metabolic pathways (e.g. TCA cycle, amino acid metabolism), but also exogenous signals arising from diet, drugs and other lifestyle and environmental stimuli, including products of microbe-host co-metabolism, which provide insight into host-gut microbiota interactions. These include short-chain fatty acids (predominantly acetate, butyrate and propionate, which have a key role in host energy metabolism), bile acids (involved in the gut-liver axis), biogenic amines (involved in the gut-brain axis) and vitamins. Metabolic phenotyping, which provides functional assessment of the gut microbiota and captures information on microbial metabolic activity following ‘biotics intervention, can aid in forming hypotheses about microbial activity that may lead to health benefits.
Challenges in determining the functions of microbes
Nevertheless, functional assessment of the microbiota remains analytically challenging. For example, human metabolic phenotypes contain information relating to different forms of optically active isomers, such as lactate and amino acids (where D- forms originate from bacteria). These enantiomers cannot be differentiated using standard metabolic phenotyping experiments, and it would be important particularly in studies identifying potential biomarkers of disease, to understand the origin of these compounds. Hence, we and others have also conducted mechanistic studies using in vitro human gut model systems (e.g. the model developed by Macfarlane et al., 1998, which has been validated against gut contents from sudden death victims and give a very close analogy to bacterial activities and composition in different areas of the hindgut), Metabolic screening of fermentation samples using metabolic phenotyping approaches provides a unique opportunity to capture dynamic microbial metabolism that is reflective of the gut microbiome in vivo, and removes contributions derived from host physiological processes (see here).
Unravelling the close interplay between microbes and host, using approaches such as metabolic phenotyping, not only provides insight into host-gut interactions, but aids our understanding of the alterations in gut microbiota mediated mechanisms that result in disease, and which demonstrate potential as therapeutic targets. More research in this area will aid in deepening understanding of the role of the gut microbiota in health and disease, and aid in the design of interventions targeting the gut microbiota (for example, the development of functional foods) for therapeutic benefit.
Food of the future: Fermented and sustainable
/in ISAPP Science Blog /by KCBy Dr. Mary Ellen Sanders, ISAPP Executive Science Officer
An exciting research initiative at the crossroads of fermented foods and sustainable diets is underway. Funded by the EU and Switzerland, and coordinated by KU Leuven in Belgium, HealthFerm is a 4-year, 13.1 MM € project involving 23 partners from 10 countries. Prof. Christophe Courtin, KU Leuven, serves as the overall project coordinator.
Scientific perspectives on fermented food is at the heart of HealthFerm. Fermented foods were defined in an ISAPP consensus paper as ‘foods made through desired microbial growth and enzymatic conversions of food components’. Predating ancient Egyptian society, fermented foods and beverages are thought to have originated over 8000 years ago, and today over 5000 varieties are enjoyed around the globe, contributing substantially to human nutrition. Fermented foods have many advantages over the raw materials from which they are made, including improved sensory characteristics, safety and stability as well as potential health benefits. How the live microbial components of fermented foods may drive the health benefits of fermented foods is an active area of research.
Prof. Courtin shares some of his thoughts about HealthFerm.
Why focus on fermentation as a means of attaining more sustainable diets?
Fermented foods have been around a long time. Why do you think now is the time to leverage their benefits?
Looking ahead, what is your greatest hope for the project?
ISAPP is represented on the HealthFerm Stakeholder Board, which convened its first meeting January 20, 2023.
ISAPP appoints new Executive Director to step into leadership role in April 2023
/in News /by KCThe board of directors of the International Scientific Association for Probiotics and Prebiotics (ISAPP) is pleased to announce the appointment of ISAPP’s next Executive Director (ED), Marla Cunningham of Brisbane, Australia. Cunningham will assume leadership of the organization April 1, 2023. ISAPP’s current ED, Dr. Mary Ellen Sanders, will stay on as Executive Science Officer until June 30, providing some overlap with Cunningham as she familiarizes herself with this new role.
Cunningham brings 20 years of experience as a scientist and business leader in the probiotic, prebiotic and natural products industry, working across innovation, clinical research, product development and education. She trained as a healthcare practitioner in complementary medicine and has written and presented extensively for clinical audiences on implementation of science in the biotics field. Cunningham has been an industry member of ISAPP for six years in her capacity as Global Research and Innovation Manager at Metagenics, and served as ISAPP’s Senior Industry Advisory Committee Representative to the board of directors for four years. She will work with ISAPP’s existing staff and board of directors to continue fulfilling the mission of the organization.
ISAPP President Dr. Dan Merenstein, who chaired the Executive Director search committee, says, “Among the excellent candidates for the Executive Director role, we determined that Marla was the best fit due to her background and previous work inside ISAPP. She is a dynamic speaker, and is always looking for ways to move ISAPP and the biotic field forward.”
Dr. Sanders says, “Marla has been an engaged member of the ISAPP community for several years and I’m confident she understands and values the unique role of ISAPP in the biotics field. With her strengths in written and oral communications, probiotic and prebiotic science, and liaison with industry, she will keep the organization dynamic and productive as it moves into this new phase.”
Sanders will remain close to the organization and intends to support Cunningham after June as needed.
“ISAPP has been a driving force in this field, fostering scientific collaboration and consensus and building a high calibre network of academic and industry scientists across the globe,” says Cunningham. “I’m excited and grateful to have the opportunity to contribute to this community in this new capacity. I’m looking forward to engaging with the ISAPP board of directors and the broader ISAPP community on the challenges and opportunities we face in the field, and developing strategic priorities to move the science forward together.”
Episode 16: The honey bee microbiome and potential for probiotics
/in Podcast, Season Two /by LauraPodcast: Play in new window | Download
Subscribe: Apple Podcasts | Spotify | RSS
The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
The honeybee microbiome and potential for probiotics, with Dr. Brendan Daisley
Episode summary:
In this episode, the ISAPP podcast hosts cover the honey bee microbiome with Brendan Daisley, PhD, who is currently a post-doctoral fellow at the University of Guelph in Canada. Daisley explains how the honeybee microbiome is unique, why it’s important for bee health, and the potential for probiotic applications as well as the practicalities of how live microorganisms are delivered to hives.
Key topics from this episode:
Episode abbreviations and links:
About Dr. Brendan Daisley:
Dr. Brendan Daisley is a postdoc at the University of Guelph (Allen-Vercoe lab) and the current President of the Students and Fellows Association of ISAPP. He graduated from his PhD in Microbiology & Immunology at Western University in 2021 (supervisor: Dr. Gregor Reid), during which he received several national awards including the Armand Frappier Outstanding Student Award, adjudicated by The Canadian Society of Microbiologists. Brendan has a broad range of experience in environmental application of probiotics to honey bees and, notably, he was the first to introduce the theory of ‘missing microbes’ within the field of honey bee microbiome research. During his PhD, he helped coordinate several large field trials across North America (mostly in Ontario and California) showing that supplementation of probiotic lactobacilli strains to honey bees could improve colony-level health outcomes. During his postdoc work, he has developed a microbiome database tool (BEExact) for improved detection of uncultivated ‘microbial dark matter’, established a bioreactor model of the honey bee gut microbiome (the RoBEEgut), and co-founded the Canadian Bee Gut Project (https://beegutproject.uoguelph.ca) – a nationwide crowdsourcing initiative that aims to deeply sequence thousands of bee microbiome samples to increase our knowledge on the multifactorial drivers of honey bee mortality.
Episode 15: A primer on prebiotics
/in Podcast, Season Two /by LauraPodcast: Play in new window | Download
Subscribe: Apple Podcasts | Spotify | RSS
The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
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:
Prebiotics alone cannot guarantee health: they must be consumed in addition to a healthy regular diet, which helps support thediversity of all gut microbes.
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.
Scientist investigating links between diet and immune system receives 2023 ISAPP Early Career Researcher Prize
/in News /by KCISAPP is pleased to announce the winner of the 2023 Glenn Gibson Early Career Researcher Prize: Paul Gill, PhD, Research Fellow at University College London, UK.
Paul’s work investigates links between diet and the immune system – in particular, how short-chain fatty acids (SCFAs) affect immunity in healthy individuals. His research found that fermented foods such as vinegar and kombucha are a rich source of SCFAs, and these may modulate immunity when consumed along with fermentable fibers. He plans to investigate the application of these findings in dietary treatment for inflammatory bowel disease.
Prior to his fellowship at University College London, Paul completed a Bachelor of Biomedical Science and a PhD in the Department of Gastroenterology, both at Monash University in Australia.
Paul Gill was identified by the ISAPP prize committee as having made significant contributions in the biotics field at an early stage in his scientific career. The award is given annually to a researcher who is no more than five years past their terminal degree, with basic or clinical research in the fields of probiotics, prebiotics, synbiotics, postbiotics or fermented foods. Additional criteria include evidence of impact through citizenship, or outreach efforts through social media or other means. He will receive a cash prize and a speaking slot at the ISAPP annual meeting in June, 2023.
Looking back and looking ahead: ISAPP session focuses on the past, present, and future of the biotics field
/in ISAPP Science Blog /by KCKristina 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
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
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.
Definition of postbiotics: A panel debate in Amsterdam
/in ISAPP Science Blog /by KCBy 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 the Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina.
A panel debate titled “Postbiotics, definition and scopes” was convened at the 9th Beneficial Microbes conference in Amsterdam on November 14, 2022. The aim of this panel was to advance the discussion about postbiotics in the aftermath of some published disagreement (see here and here) about the definition of postbiotics produced and published by ISAPP: “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”. The debaters included Prof. Seppo Salminen and myself (Dr. Gabriel Vinderola), both members of the board of directors of ISAPP and co-authors of the ISAPP postbiotics definition, supporting the ISAPP definition, and Prof. Lorenzo Morelli (in attendance virtually) and Dr. Guus Roeselers challenging the ISAPP definition. The debate was attended by around 150 persons, and consisted of 15-minute opening arguments on both sides, followed by a 30 min open discussion guided by the conference chair, Dr. Koen Venema.
I introduced ISAPP as a non-profit organization dedicated to advancing the science on probiotics, prebiotics and related substances. Among many other activities, ISAPP has produced 5 different consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods. Each consensus panel was composed of academic scientists with different backgrounds, expertise and perspectives, comprising at least 11 authors from 4 – 10 countries, who came together to incorporate broad perspectives and engage in thoughtful debate. To date, all 5 consensus papers have had almost half a millon accesses at Nature Reviews Gastroentetology and Hepatology, the journal where all of the definitions are published.
The discussion within ISAPP about the need for a postbiotic definition dates back to our 2019 annual meeting. Emerging research on the health benefits conferred by non-viable microbes, their fragments and metabolites was discussed at the meeting, and this planted the seed for a definition that would cover this area. Many different terms such as heat-killed probiotics, heat-treated probiotics, heat-inactivated probiotics, tyndallized probiotics, paraprobiotics, ghost probiotics, cell fragments, cell lysates and postbiotics had been used to encompass these substances.
The panel discussed these different terms and previously published definitions. Those opposed to the ISAPP definition preferred the Tsilingiri and Rescigno (2013)1 definition of postbiotics, which focuses on metabolites produced by probiotics. I reviewed the limitations of that definition, which were outlined in Salminen et al. (2021)2. One concern is that requiring a postbiotic to be derived from a probiotic creates an unnecessary burden of first meeting the criteria for a probiotic before developing a postbiotic.
Morelli emphasized the importance of definitions for regulatory bodies and stated that researchers should provide guidance on criteria to meet a definition. He quoted the first published definition of postbiotic by Tsilingiri and Rescigno in 20131: “any factor resulting from the metabolic activity of a probiotic or any released molecule capable of conferring beneficial effects to the host in a direct or indirect way”. Morelli stated that one value of this definition was that it was clear to regulators; metabolites are measurable and produced by microbes already accepted as food components with a long history of safe use. He considered this of paramount relevance as otherwise, the novel foods path would be required. He challenged the ISAPP approach as defining a substance that was unclear how to measure. Morelli showed pictures depicting the deterioration of the biomass of freeze-dried cultures during storage, to underscore the challenges of controlling the quality of products based on biomass of non-viable microbes. He added, “If we don´t know which are the components responsible for the health benefits, then it is challenging to determine what to measure.” He questioned the ability to establish the shelf life of such a product. The need to be precise in terms of how to quantify the active components of non-viable cells was essential to his criticism of ISAPP’s definition of postbiotics. Prof. Morelli concluded that researchers must address this issue of quantification methods, both to advance research and to provide regulatory bodies needed approaches to regulating non-viable microbes.
Conclusions from the debate were that the flaws of definitions previous to the ISAPP definition are apparent, and that the substance defined by ISAPP was useful to delineate, but that clear approaches to measurement of the active component(s) of non-viable microbes are needed to make the ISAPP definition workable in scientific and regulatory circles. The debate was very worthwhile, since science advances through respectful debates such as this.
It is clear that characterization of postbiotic products may be challenging, especially with increased complexity that arises by use of multiple inanimate strains, inclusion of metabolic endproducts, and the presence of whole and fragmented cells. But these challenges are not unique to postbiotics. Probiotic products can comprise complex mixtures of multiple strains as well as metabolic products (as the biomass during industrial production is harvested for freeze-drying, but not washed), along with significant amounts of non-viable microbes, which all may contribute to the overall health benefit. These facts are usually overlooked when relying just on viable cells for quantification.
Many commercial products carrying inanimate microbes and metabolic fermentation products, that potentially fit the ISAPP definition of postbiotics, are already available in the market. These are diverse products such as a mixture of two lactobacilli aimed at treating infant and adult diarrhea3 or a fermented infant formula to support pediatric growth4. Similar products also target animal nutrition5. A tightly controlled manufacturing process may be the path forward to warrant reproducibility of health benefits. Suitable characterization methodologies such as flow cytometry for non-viable microbes and mass spectrometry for metabolites seem to be relevant to sufficient postbiotic product characterization.
In brief, the ISAPP definition itself seemed well accepted by the meeting participants, but concerns were raised about how to quantify postbiotics according to the definition. We intend to address this point through consultations with experts, proposing scientific paths to help conceptualize factors that need to be considered for postbiotic quantification.
Panel debate about ISAPP’s definition of postbiotics held at Beneficial Microbes conference in Amsterdam on November 14th, 2022. On the stage, from left to right: Koen Venema (conference chair), Gabriel Vinderola, Seppo Salminen, Guus Roeselers and Lorenzo Morelli (on screen).
References
Watch / listen to the debate here: https://youtu.be/pATNfhQY4P4
The many functions of human milk oligosaccharides: A Q&A with Prof. Ardythe Morrow
/in ISAPP Science Blog /by KCHuman milk is the ‘gold standard’ of infant nutrition—and some scientists have set their sights on working towards that standard to improve the health of infants who are not breastfed. Among the many important components of human milk are human milk oligosaccharides (HMOs): complex carbohydrates that are 3-32 sugars in length. Over 200 different HMO molecules have been discovered, but a mother typically has between 12 and 20 in her milk. Some types of HMOs are affected by genetic polymorphisms – for example, only those who have the FUT2 (secretor) gene have breast milk containing HMOs called 2′-fucosylated (2’-FL) glycans.
ISAPP held a webinar in October, 2022 featuring Prof. Ardythe Morrow, University of Cincinnati College of Medicine, speaking about the latest research on HMOs and their health effects in both infants and adults.
HMOs as prebiotics
Prof. Morrow emphasized that research to date on HMOs shows they clearly fit the scientific consensus definition for prebiotics: a “substrate that is selectively utilized by host microorganisms conferring a health benefit”. HMOs are utilized by bacteria in the infant gut—mainly bifidobacteria, but also other genera (Yu, Chen & Newburg, 2013)—producing end-products that benefit infant health. B. longum subsp. infantis are the quintessential bacteria that grow on HMOs; pathogens do not typically grow on them.
Within the prebiotic category, HMOs are unique. Unlike other prebiotic substances they are structurally similar to gut oligosaccharides, which populate the surface of mucosal surfaces of the GI tract and are abundant in the mucin layer. They also can function via mechanisms that do not require utilization by gut microbes.
Beyond prebiotic function
Prof. Morrow emphasized that HMOs are multi-functional agents: in addition to their prebiotic functions, they have direct functions in the infant gut that are not mediated by microbes. First, individual HMOs have been shown to bind pathogens and inhibit infections and bind to immune cells to optimize their function (Triantis, Bode & van Neerven, 2018). Further, they can enhance neurodevelopment and brain function (Furness, Kunze & Clerc 1999; Sharon et al, 2016). The latter is a more recent domain of research, but so far it is known that basic neurodevelopmental processes are modulated in animals that are germ-free or have a depleted gut microbiota.
Certain HMOs (notably 2’-FL) can be produced synthetically and are being tested in infant formulas, and more recently for healthy adults (Elison et al., 2016). Prof. Morrow noted HMOs also have potential as novel therapeutics for various indications, such as inflammatory bowel disease (IBD). Determining which specific HMOs are most effective in these outcomes, and the dose needed, is an active area of research.
The webinar participants generated some interesting questions, some of which Prof. Morrow answers below.
Are 2’FL and LNnT (Lacto-N-neotetraose) found in cow’s milk?
2′-FL is not found in cow’s milk. Other oligosaccharides, especially sialyl oligosaccharides, are present but generally at very low levels.
How similar to HMOs are the glycosylation patterns on gut mucin?
Mucin glycosylation is not identical to human milk. But there are structural motifs that recur in both milk and gut mucin.
Do the more abundant HMOs have more potential for health benefit, compared with those at lower abundances in human milk?
We do not know that more abundance means more functionality or importance. But it is a reasonable place to start with the research. Also, several of the most abundant HMOs are trisaccharides (2’FL, 3FL, 3′-SL, and 6′-SL), and these are the most manageable to synthesize and start with.
For non-secretors, HMO complexity in milk is around 30% lower than for secretors. Does this factor affect the beneficial functions of non-secretor HMOs?
Having lower HMO content might be an issue in some circumstances. But we cannot say that it is a general problem. Furthermore, if non-secretors have more sialyloligosaccharides and 3-FL instead of 2′-FL, for example, perhaps this helps protect against viruses that bind to sialic acid epitopes (for example, influenza). Or perhaps this helps with increasing sialic acid to the brain (see Mudd et al., 2017). So, my argument is that at this point in our knowledge, we should avoid any idea of “superior” or “inferior” milk for the general healthy public. More likely, there are situation-specific benefits or disadvantages for different milk oligosaccharide phenotypes.
What do you think is more important for infant formula, more HMO complexity or more structure-function relations?
A set of HMOs for normal infant nutrition will be important, and these include fucosyllactoses, sialyllactoses, and neutral oligosaccharide with neither sialic acid nor fucose. Structure-function orientation is important to guide use in special populations with specific health needs.
Long term, will HMOs replace FOS and GOS in infant formulas?
All of the efforts in making infant formula have the goal of doing the best possible job of mimicking the physiological function of breastmilk, but cost and function are also relevant factors to consider in this process. It’s important that babies get some form of prebiotic. GOS is structurally more similar to HMOs, but it’s not enough on its own. Ideally, we’d hope for a rational mixture of different oligosaccharides backed by research confirming their combined functions.
Can we really replicate HMOs with synthetic formula, given the large number of diverse HMOs present in human milk?
I do not foresee ever achieving full replication, no. But getting closer to mother’s milk, yes, over time.
How is the dosing of HMOs in clinical trials for adults being determined? Should it be based on human milk concentration?
Elison et al. published a dosing study based on tolerance and shift of microbiota. A dosing study is now underway in Cincinnati, too.
Since it is fairly difficult to manufacture HMOs, do you think they provide sufficient advantages compared to GOS to justify their use as prebiotics in adults?
We do not yet know whether HMOs might have enough advantage over GOS in some situations, or whether prebiotic combinations might be best. This is research in progress! The reason for testing 2′-FL in IBD is because of the structure-function evidence. IBD is increased in non-secretors, and is associated with dysbiosis, inflammation, and so on. We will learn from the ongoing research.
Do you think adults will differ in response to HMOs therapeutically, possibly based on genetic differences?
I don’t yet have data on this, but have a study ongoing that I hope will be able to address this very question.
Watch the recording of this webinar below:
Episode 14: Evidence on probiotics for preterm infants
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The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and 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:
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.
Shaping microbial exposures and the immune system in childhood: Can sandboxes be probiotic?
/in ISAPP Science Blog, Consumer Blog /by KCBy Prof. Seppo Salminen, University of Turku, Finland
Gut microbiota researchers have established that microbial exposures in early life can be influential on health later in life. Children who develop asthma in early childhood, for example, have an altered gut microbiota linked with exposure to less diverse microorganisms in their first year. The ‘biodiversity hypothesis’ has been advanced recently, suggesting that western lifestyles and low biodiversity in urban environments reduce contact with microbes both via food and via the natural environment, presenting fewer opportunities for children to be exposed to a diversity of microbes in their earliest years and increasing the risk of non-communicable diseases. If this is the case, the environments of daycare and kindergarten facilities come under scrutiny as a source of microbial exposures at a crucial time of life. So is it beneficial to intervene in children’s environments to ensure more diverse microbial exposures? Can we enhance gut microbial diversity and richness in children through environmental interventions?
A new study provided proof that shaping children’s microbial exposures may be possible. The study was the first of its kind – a placebo-controlled, double-blinded study on the effect of environmental exposures on gut microbiota diversity and immune parameters in young children. The study used playground sandboxes at daycare facilities as sources of environmental microbial diversity and explored whether these could have effects on the children.
Six day-care centers in southern Finland were enrolled in the study, with two randomly assigned to intervention and four to placebo. Identical-looking playground sandboxes were used. Intervention sandboxes were filled with sand of glacial origin enriched with a known biodiversity powder (including commercial soil, deciduous leaf litter, peat, and Sphagnum moss; described in detail by Hui et al., 2019 ; Grönroos et al, 2018). In control centers the sand was regular sandbox sand and placebo peat material. Altogether, 26 children ages 3-5 participated in supervised play for 20 minutes in the morning and afternoon for two weeks. Researchers measured the composition of gut and skin microbiota, as well as blood immune markers.
The results demonstrated that exposure to diverse environmental microbiota enhanced both the bacterial richness and diversity of the skin bacterial community. The microbiome of the skin changed only in those children who had played in a sandbox enriched with natural materials. The authors also found that the daily exposure to higher microbial biodiversity resulted in positive differences in immune response. For instance, the authors reported shifts in skin microbiota associated with IL-10 and T cell frequencies. This provides the first evidence from a placebo-controlled, double-blinded study in young children showing the differential effects on microbiota and immunity of daily exposure to defined microbial biodiversity.
An interesting follow-up could be using sandboxes to deliver probiotics with a proven health impact to children. Since the sandbox microbes were shown to influence children’s immune systems, could researchers go one step further and modulate children’s microbiota in a targeted manner? A probiotic must be defined, shown to have a health benefit and administered in an efficacious dose. In the case of sandboxes, the health benefit would need to be demonstrated for a certain level or duration of environmental exposure.
Playgrounds and sandboxes require materials that tolerate heavy wear and tear and are safe at the same time. Such materials need to be kept free of unnecessary contamination as sandboxes, for example, can also be good reservoirs of some detrimental bacteria. Therefore, it could be important to have defined natural materials for a positive impact on health. In the future, we may see many creative approaches to ensuring children receive appropriate health-supporting microbial exposures early in life. However, creating probiotic approaches requires identification of specific microbes in the biodiversity powder.
Episode 13: The history of ISAPP
/in Podcast, Season One /by KCPodcast: Play in new window | Download
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The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and 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:
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 12: Postbiotics and probiotics in Japan: A researcher’s perspective
/in Podcast, Season One /by KCPodcast: Play in new window | Download
Subscribe: Apple Podcasts | Spotify | RSS
The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
Postbiotics and probiotics in Japan: A researcher’s perspective, with Prof. Akihito Endo
Episode summary:
In this episode, ISAPP podcast host Dan Tancredi talks with food microbiologist Prof. Akihito Endo from Tokyo University of Agriculture in Japan, who was an author on the published ISAPP scientific consensus definition of postbiotics. Endo describes the unique properties of fructophilic lactic acid bacteria, and talks about the landscape of probiotic and postbiotic products in Japan.
Key topics from this episode:
Episode abbreviations and links:
The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics
Mitsuoka T. 1998. Functional Food: Probiotics, Prebiotics, Biogenics. Intestinal Flora and Probiotics.
Mitsuoka. 2011. History and Evolution of Probiotics. Japanese Journal of Lactic Acid Bacteria.
Background on fructophilic lactic acid bacteria: Are fructophilic lactic acid bacteria (FLAB) beneficial to humans?
Viable fructophilic lactic acid bacteria present in honeybee-based food products
Japanese categories for health benefit claims on foods (for more details, see ISAPP consensus statement):
On Kikunae Ikeda’s discovery of umami: Glutamate: from discovery as a food flavor to role as a basic taste (umami)
Additional resources:
Behind the publication: Understanding ISAPP’s new scientific consensus definition of postbiotics. ISAPP blog
Postbiotics. ISAPP infographic
What is a postbiotic? ISAPP video
About Prof. Aki Endo:
Akihito Endo is a research professor at Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Japan. He obtained a PhD degree of Fermentation Science with a topic on Lactic Acid Bacterial Diversity during Shochu Fermentation at Tokyo University of Agriculture in 2005. After he studied as a postdoc in Stellenbosch University (South Africa) and in University of Turku (Finland), he started to work in Tokyo University of Agriculture in 2013. His research themes are ecology and food application of fructophilic lactic acid bacteria and oligosaccharide metabolism in human gut anaerobes. He is a member of Subcommittee on the taxonomy of Bifidobacterium, Lactobacillus and related organisms, International Committee on Systematics of Prokaryotes since 2011 and a board member of Japanese Society for Lactic Acid Bacteria since 2021.
Why researchers need to understand more about the small intestinal microbiome
/in ISAPP Science Blog /by KCBy Prof. Eamonn M. M. Quigley, MD, The Methodist Hospital and Weill Cornell School of Medicine, and Prof. Purna Kashyap, MD, Mayo Clinic
The phrase “gut microbiota” properly refers to the microorganisms living throughout the entire digestive tract, including the mouth and the upper digestive tract, through the length of the small intestine as well as the large intestine. Yet the vast majority of scientific studies on the gut microbiota make conclusions based only on stool samples, meaning that the contributions to health and disease of microorganisms from most of the digestive tract are largely unexplored.
Researchers have established that the microorganisms throughout different parts of the digestive tract vary greatly. In particular, the microorganisms living in the small intestine are fewer in number than those in the colon. They are less diverse, and they change more over time because of their dynamic environment (fluctuations in oxygen, digestive secretions, dietary substrates, among other influences).
The dynamic composition and biologic functions of the small intestinal microbiome in health and disease are mostly unknown. Research has been hampered by the difficulty in obtaining samples from this area of the digestive tract and, in particular, its more distal reaches. Participants in a 2022 ISAPP discussion group argued, however, there are some good reasons to dedicate more effort to investigation of the small intestinal microbiome:
How can we gain more information on the small intestinal microbiome? Our group tackled the limitations of current definitions and diagnostic methods, noting that this field may be advanced in the near future by new technologies for real-time sampling of intestinal gases and contents. The group discussed optimal methods for the sampling of small intestinal microbes and their metabolic products—noting that a full range of ‘omics technologies applied in well-defined populations could lead to further insights. In the meantime, the gastroenterologists in our group advised restraint in the diagnosis of SIBO and the need to exert caution in identifying it as the cause of symptoms. Clinical progress in this area is best achieved through the application of modern molecular methods to the study of human small intestinal microorganisms.
Episode 11: How to build a satisfying scientific career and make a difference
/in Podcast, Season One /by KCPodcast: Play in new window | Download
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The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
How to build a satisfying scientific career and make a difference, with Prof. Gregor Reid
Episode summary:
In this episode, the ISAPP podcast hosts talk about how to succeed as a scientist in the fields of probiotics and prebiotics with Gregor Reid, professor emeritus at Western University, Canada. Prof. Reid, who is ISAPP’s former president and host of the first ISAPP meeting 20 years ago, tells about his career path and shares ways to make a difference outside of the scientific laboratory.
Key topics from this episode:
Episode abbreviations and links:
Landmark papers related to vaginal lactobacilli, biofilms and health:
Recurrent urethritis in women
Bacterial biofilm formation in the urinary bladder of spinal cord injured patients
Bacterial biofilms: influence on the pathogenesis, diagnosis and treatment of urinary tract infections
Ultrastructural study of microbiologic colonization of urinary catheters
Additional resources:
Reflections on a career in probiotic science, from ISAPP founding board member Prof. Gregor Reid. ISAPP blog
The Children of Masiphumelele Township. ISAPP blog
About Prof. Gregor Reid:
Gregor Reid is a Fellow of the Royal Society of Canada and Canadian Academy of Health Sciences, and Distinguished Professor Emeritus at Western University.
Born and raised in Scotland, he did his PhD in New Zealand and immigrated to Canada in 1982. His research, most recently at Lawson Health Research Institute, has focused on the role of beneficial microbes in the health of humans and other life forms. He has produced 32 patents, 586 peer-reviewed publications cited over 50,000 times, has a Google Scholar H index of 116 and has given over 650 talks in 54 countries. He is ranked #3 in Canada and #59 in the world for Microbiology Scientists by research.com. In 2001, he chaired the UN/WHO Expert Panel that defined the term probiotic. In 2004, he helped introduce probiotic yoghurt to East Africa as a means for women to create microenterprises that by 2019 reached 260,000 adults and children.
He has received an Honorary Doctorate from Orebro University, Sweden, a Distinguished Alumni award from Massey University, New Zealand, a Canadian Society for Microbiologists Career Award and Western University’s highest accolade of Distinguished Professor. He is Chief Scientific Officer for Seed, a Californian start-up.
Episode 10: How the ISALA project investigates what makes a healthy vaginal microbiome
/in Podcast, Season One /by KCPodcast: Play in new window | Download
Subscribe: Apple Podcasts | Spotify | RSS
The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
How the ISALA project investigates what makes a healthy vaginal microbiome, with Prof. Sarah Lebeer
Episode summary:
In this episode, the ISAPP hosts discuss what’s known about the healthy vaginal microbiome with Prof. Sarah Lebeer from University of Antwerp, Belgium. Lebeer describes the citizen science project she leads in Belgium called “ISALA” and outlines its findings to date. She also talks about important questions remaining to be answered in the field.
Key topics from this episode:
Episode abbreviations and links:
ISALA project website (English)
Important probiotic trials focused on women’s health:
Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial
Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis
Effect of Oral Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the Vaginal Microbiota, Cytokines and Chemokines in Pregnant Women
Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence
Trials of vaginal microbiota transplantation:
Vaginal microbiome transplantation in women with intractable bacterial vaginosis
Additional resources:
Citizen scientists step up for a research project on women’s health. 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.
Are probiotics effective in improving symptoms of constipation?
/in ISAPP Science Blog, Consumer Blog /by KCBy Eirini Dimidi, PhD, Lecturer at King’s College London
Constipation is a common disorder that affects approximately 8% of the general population and is characterised by symptoms of infrequent or difficult bowel movements (1). People who suffer with constipation often report that it negatively affects their quality of life and the majority use some sort of treatment, such as fibre supplements and laxatives, to alleviate their symptoms (2). However, approximately half of those report they are not completely satisfied with the treatment options currently available to them, mainly due to lack of effectiveness in improving their symptoms (2).
Could probiotics offer an effective alternative way to treat constipation symptoms?
Our team at the Department of Nutritional Sciences at King’s College London has investigated the potential benefits of probiotic supplements in chronic constipation. We have extensively reviewed the available evidence on their mechanisms of action in affecting gut motility and their effectiveness in improving symptoms, and we have also conducted a randomised controlled trial of a novel probiotic in 75 people with chronic constipation (3-5).
USE OF PROBIOTICS
Before looking at the evidence on the effectiveness of probiotics in constipation, it is easy to see that some people with constipation already choose to try probiotics for their gut health. A national UK survey of over 2,500 members of the public, which included people with and without constipation, showed that people with constipation have a 5.2 higher chance of currently using probiotics for gut health, compared to people who don’t suffer from it (3).
However, the majority of doctors do not recommend probiotics for the relief of constipation symptoms, nor do they believe there is enough evidence to support their use in this condition (3).
So, what is the current evidence on probiotics and constipation?
MECHANISMS OF ACTION OF PROBIOTICS
Probiotics may impact gut motility and constipation through several mechanisms of action. Depending on the strain, they may affect the number and composition of gut microbes, as well as the compounds they release. The gut microbiota and their released compounds can then interact with our immune and nervous system, with the latter being the primary regulator of gut motility, ultimately improving constipation symptoms. Therefore, there is a rationale to support a potential improvement in constipation. But is this supported by evidence from clinical trials?
EFFECTIVENESS OF PROBIOTICS
A systematic review of the literature showed Bifidobacterium lactis strains appear to improve several symptoms of constipation, such as infrequent bowel movements and hard stools (4). At the same time, other probiotic species did not improve any symptoms. This is an important finding as it highlights that not all probiotics have the same effects in constipation, and that only certain probiotics may improve constipation. Therefore, people with constipation may only benefit from specific probiotic products – but which products would those be? Since the systematic review above showed that several B. lactis strains were effective, does this means that people with constipation may benefit from any B. lactis-containing product?
Unfortunately, it is a bit more complicated. Since the publication of the aforementioned review, new studies have been published showing that, while some probiotic products with B. lactis are effective, various other B. lactis probiotics do not impact constipation (5-6). This may be explained by strain-specific effects, but also other methodological differences among studies (e.g. probiotic dose).
TAKE HOME MESSAGE
Can we recommend probiotics for the management of constipation? At the moment, there is some low quality evidence to support the use of certain Bifidobacterium lactis strains to help manage symptoms of constipation. Further high-quality studies are needed to clarify which specific probiotic strains may be effective. However, given that there is some evidence in this area (albeit limited), along with the fact probiotics are safe for the general population to consume (unless clinically contraindicated), people with constipation could try a probiotic product of their choice for four weeks, should they wish to, bearing in mind the uncertainty in the evidence so far. But scientists continue to work to answer this question because the evidence is promising enough to warrant continued study of probiotics for constipation.
Episode 9: An evolutionary perspective on fermented foods
/in Podcast, Season One /by KCPodcast: Play in new window | Download
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The Science, Microbes & Health Podcast
This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.
An evolutionary perspective on fermented foods, with Assoc. Prof. Katie Amato
Episode summary:
In this episode, the ISAPP hosts talk about fermented foods and non-human primates with Katie Amato of Northwestern University, USA. Amato describes what she has learned from studying the gut microbiota of non-human primates and how it relates to our understanding of human and gut microbial co-evolution over time. She also talks about non-human primate behaviors around fermented foods and what they might tell us about the need for human fermented food consumption.
Key topics from this episode:
Episode abbreviations and links:
Dissertation study: The Gut Microbiota Appears to Compensate for Seasonal Diet Variation in the Wild Black Howler Monkey (Alouatta pigra)
Study: Fermented food consumption in wild nonhuman primates and its ecological drivers
Mentors mentioned: Kathy Cottingham, Matt Ayres, David Peart, John Gilbert, Mark McPeek, Craig Layne, Rob McClung.
Steve Ross, Alejandro Estrada, Paul Garber, Angela Kent, Rod Mackie, Steve Leigh, Rob Knight.
Additional resources:
Research on the microbiome and health benefits of fermented foods – a 40 year perspective. ISAPP blog
New ISAPP-led paper calls for investigation of evidence for links between live dietary microbes and health. ISAPP blog
About Assoc. Prof. Katie Amato:
Dr. Amato is a biological anthropologist at Northwestern University studying the influence of gut microbes on host ecology and evolution. Her research examines how changes in the gut microbiota impact host nutrition, energetics, and health. She uses non-human primates as models for studying host-gut microbe interactions in selective environments and for providing comparative insight into the evolution of the human gut microbiota. Her main foci are understanding how the gut microbiome may buffer hosts during periods of nutritional stress and how the gut microbiome programs normal inter-specific differences in host metabolism. Dr. Amato is the President of the Midwest Primate Interest Group, an Associate Editor at Microbiome, an Editorial Board member at Folia Primatologica, and a Fellow for the Canadian Institute of Advanced Research’s ‘Humans and the Microbiome’ Program.