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Episode 11: How to build a satisfying scientific career and make a difference

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:

  • The importance of keeping a sense of humor as a scientist
  • Sometimes it pays to do something unconventional: early in his career, Reid decided to work with a urologist who had a hunch that lactobacilli were important in women’s health; they had difficulty getting funding to investigate further but they persisted over a number of years and eventually published some landmark work
  • Reid (with others) investigated on how biofilms impacted clinical antibiotic treatments
  • When clinical problems drive the research, it can have great impact on people’s lives, yet it can take many years to progress from observation to mechanism to better clinical treatments
  • Probiotics are “an ecological approach to an ecological problem” but often the structures (funding, regulatory, etc.)  are not in place for scientists to study them or pursue them as interventions in industry
  • Prof. Reid has worked in South Africa, led by local people, helping them obtain tools for making fermented yogurt (Yoba-For-Life)
  • For early career scientists who want to make a difference in science beyond publishing papers, it’s important to be proactive and go after what you want
  • The right lab and the right environment are essential
  • Reflect on the personal connection to your work that “makes you almost unstoppable”
  • Partnerships are key for international impacts
  • Those involved in ISAPP can champion a cause that’s important to them within the organization
  • Flexibility will be key for probiotics (and other ‘biotics’) companies in the future
  • The field is poised to expand; all kinds of organisms will benefit from probiotics in the future

 

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. 

Can diet shape the effects of probiotics or prebiotics?

By Prof. Maria Marco PhD, University of California – Davis and Prof. Kevin Whelan PhD, King’s College London

If you take any probiotic or prebiotic product off the shelf and give it to several different people to consume, you might find that each person experiences a different effect. One person may notice a dramatic reduction in gastrointestinal symptoms, for example, while another person may experience no benefit. On one level this is not surprising, since every person is unique. But as scientists, we are interested in finding out exactly what makes a person respond to a given probiotic or prebiotic to help healthcare providers know which products to recommend to which people.

Among factors that might impact someone’s response to a probiotic or prebiotic – such as baseline microbiota, medications, and host genetics – diet emerges as a top candidate. Ample evidence has emerged over the past ten years that diet has direct and important effects on the structure and function of the gut microbiome. Overall the human gut microbiome is shaped by habitual diet (that is, the types of foods consumed habitually over time), but the microbes can also can fluctuate in response to short-term dietary shifts. Different dietary patterns are associated with distinct gut microbiome capabilities. Since probiotics and prebiotics may then interact with gut microbes when consumed, it is plausible that probiotic activity and prebiotic-mediated gut microbiome modulation may be impacted by host diet.

A discussion group convened at ISAPP’s 2022 annual meeting brought together experts from academia and industry to address whether there is evidence to support the impact of diet on the health effects of probiotics and prebiotics. To answer this question, we looked at how many probiotic or prebiotic studies included data on subjects’ diets.

  • Prebiotics: Our review of the literature showed that only a handful of prebiotic intervention studies actively measured background diet as a potential confounder of the effect of the prebiotic. One such study (Healey, et al., 2018) classified individuals based on habitual fiber intake, and in doing so found that the gut microbiome of individuals consuming high fiber diets exhibited more changes to microbiome composition than individuals with low fiber intake. While both groups consuming prebiotics showed enrichment of Bifidobacterium, those with high fiber intake uniquely were enriched in numerous other taxa, including butyrate-producing groups of microbes. Prebiotics also resulted in improved feelings of satiety, but only among the high fiber diet consumers.
  • Probiotics: We found no evidence of published human RCTs on probiotics that investigated diet as a possible confounding factor. This is a significant gap, since we know from other studies that host diet affects the metabolic and functional activity of probiotic lactobacilli in the digestive tract. Moreover, the food matrix for the probiotic may further shape its effects, via the way in which the probiotic is released in situ.

Our expert group agreed that diet should be included in the development of new human studies on probiotics and prebiotics, as well as other ‘-biotics’ and fermented foods. These data are urgently needed because although diet may be a main factor affecting outcomes of clinical trials for such products, it is currently a “hidden” factor.

We acknowledge there will be challenges in taking diet into account in future trials. For one, should researchers merely record subjects’ habitual dietary intake, or should they provide a prescribed diet for the duration of the trial? The dietary intervention (nutrient, food, or whole diet) must also be clearly defined, and researchers should carefully consider how to measure diet (e.g. using prospective or retrospective methods). In the nutrition field, it is well known that there are challenges and limitations in the ways dietary intake is recorded as well as the selection of dietary exclusion criteria. Hence, it is crucial that dietitians knowledgeable in dietary assessment and microbiome research contribute to the design of such trials.

If more probiotic and prebiotic trials begin to include measures of diet, perhaps we will get closer to understanding the precise factors that shape someone’s response to these products, ultimately allowing people to have more confidence that the product they consume will give them the benefits they expect.

Human milk oligosaccharides as prebiotics to be discussed in upcoming ISAPP webinar

Human milk oligosaccharides (HMOs), non-digestible carbohydrates found in breast milk, have beneficial effects on infant health by acting as substrates for immune-modulating bacteria in the intestinal tract. The past several years have brought an increase in our understanding of how HMOs confer health benefits, prompting the inclusion of synthetic HMOs in some infant formula products.

These topics will be covered in an upcoming webinar, “Human milk oligosaccharides: Prebiotics in a class of their own?”, with a presentation by Ardythe Morrow PhD, Professor of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine. The webinar will provide an overview of what HMOs are, how they are breaking new ground with the types of health benefits they can provide to infants and the recent technological innovations that will facilitate their translation into new infant formulas.

Dr. Karen Scott, Rowett Institute, University of Aberdeen, and Dr. Margriet Schoterman, FrieslandCampina, will host the webinar. All are welcome to join this webinar, scheduled for Wednesday, Oct 19th, 2022, from 10-11 AM Eastern Daylight Time. Registration is free of charge. Spaces may be limited.

Register here.

Episode 5: Prebiotics for animal health

The Science, Microbes & Health Podcast 

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

Prebiotics for animal health, with Prof. George Fahey

Episode summary:

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

Key topics from this episode:

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

 

Episode links:

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

 

Additional resources:

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

 

About Prof. George Fahey:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

 

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

 

ISAPP’s 2021 year in review

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

The upcoming year-end naturally leads us to reflect about what has transpired over the past 12 months. From my perspective working with ISAPP, I witnessed ISAPP board members and the broader ISAPP community working creatively and diligently to find solutions to scientific challenges in probiotics, prebiotics and related fields. Let’s look back together at some of the key developments of 2021.

ISAPP published outcomes from two consensus panels this year, one on fermented foods and one on postbiotics. The popularity of these articles astounds me, with 49K and 29K accesses respectively, as of this writing. I think this reflects recognition on the part of the scientific community of the value – for all stakeholders – of concise, well-considered scientific definitions of terms that we deal with on a daily basis. If we can all agree on what we mean when we use a term, confusion is abated and progress is facilitated. The postbiotics definition was greeted with some resistance, however, and it will remain to be seen how this is resolved. But I think ISAPP’s response about this objection makes it clear that productive definitions are difficult to generate. Even if the field ultimately embraces another definition, it is heartening to engage in scientific debate about ideas and try to find alignment.

Keeping with the idea of postbiotics, a noteworthy development this year was the opinion from the European Food Safety Authority that the postbiotic made from heat-treated Akkermansia muciniphila is safe for use as a novel food in the EU. Undoubtedly, this development is a bellwether for likely future developments in this emerging area as some technological advantages to postbiotics will make these substances an attractive alternative to probiotics IF the scientific evidence for health benefits becomes available.

Recognizing the existing need for translational information for clinicians, ISAPP developed a continuing education course for dietitians. Published in March, it has currently reached close to 6000 dietitians. This course focused on probiotics, prebiotics and fermented foods: what they and how they might be applied in dietetic practice. It is a freely available, self-study course and completion provides two continuing education credits for dietitians.

On a sad note, in March of this year, ISAPP suffered the loss of Prof. Todd Klaenhammer. Todd was a founding ISAPP board member, and directed many of our activities over the course of his 18-year term on the board. He was also my dear friend and major advisor for my graduate degrees at NC State many years ago.  As one former collaborator put it, “I was not prepared to finish enjoying his friendship and mentorship.” See here for a tribute to Prof. Klaenhammer on the ISAPP blog: In Memoriam: Todd Klaenhammer.

So where will 2022 lead ISAPP? The organization has now published five consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods – extending its purview beyond where it started, with probiotics and prebiotics. Through the year ahead, ISAPP is committed to providing science-based information on the whole ‘biotics’ family of substances as well as fermented foods. Our Students and Fellows Association is growing, supported by the opportunity for young scientists to compete for the Glenn Gibson Early Career Researcher Prize. We continue to see our industry membership expand. Through our new Instagram account and other online platforms, our overall community is increasing. The ISAPP board of directors continues to evolve as well, with several long-term members leaving the board to make room for younger leaders in the field who will direct the future of the organization. This applies to me as well, as I have made the difficult decision to depart ISAPP in June of 2023. Thus, hiring a new executive director/executive science officer is an important priority for ISAPP in 2022. My 20 years with ISAPP have seen the organization evolve tremendously, through the hard work of incredible board members as well as many external contributors. We will strive to make 2022 – our 20th anniversary – ISAPP’s best year yet.

Hands holding mobile phone

Virtual events continue to fill gaps as in-person meetings are being planned

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

For scientists, annual meetings provide coveted opportunities to hear about the latest scientific advances from expert researchers, and they are where students and trainees get to present their research, often for the first time. Of course, meeting and socializing with colleagues, both new and old, during breaks and evening sessions is also an important part of these conferences.

Yet over the past two years, most occasions to meet face-to-face were canceled. Virtual meetings became the new normal and, even though a poor substitute for in-person gatherings, provided opportunities to connect and share emerging science. As we anticipate being together again in person – hopefully for 2022 meetings – take note of three upcoming conferences to fill the gap. Each of these feature meetings are related to the gut microbiome, diet, and health.

(1) In October, the Agriculture and Health Summit: Cultivating Gut Health at the Crossroads of Food & Medicine is a FREE three-day virtual conference that brings together a unique combination of researchers, industry leaders and thought leaders from the biomedical and agricultural sectors for important conversations about the future of human health. The event will provide a rare opportunity for individuals with diverse areas of expertise to discuss opportunities and challenges in creating ‘foods for health’ through the gut microbiome, working toward solutions in nutrition and medicine. More information can be found here. Among the presenters are ISAPP Executive Science Officer, Mary Ellen Sanders, and board members, Dan Merenstein and Bob Hutkins.

 

(2) Then in November, a Nature-sponsored online conference called Reshaping the Microbiome through Nutrition will be held. According to the website, “this conference will bring together researchers working on the microbiome and nutrition to discuss how our microbiota use and transform dietary components, and how these nutrients and their products influence host health throughout life, including effects on development and infectious and chronic diseases. A central theme of the meeting will be how diet and dietary supplements could be harnessed to manipulate the microbiome with the aim of maintaining health and treating disease”More information is found here.

(3) Another meeting in November is organized across ten centers/institutes at the NIH and the Office of Dietary Supplements and the Office of Nutrition Research. This two-day conference November 5 and 8, titled Precision Probiotic Therapies—Challenges and Opportunities, features a Keynote address by Prof. Jeff Gordon, from the Washington University School of Medicine. ISAPP president Prof. Dan Merenstein, Georgetown University School of Medicine, is also presenting. To register for this FREE meeting, see here.

 

In this current era, interest in how diet (including probiotics, prebiotics, and fermented foods) influences the microbiome and affects human and animal health has never been greater, as is evident by these and other similarly-themed conferences.

ISAPP is planning its next annual by-invitation meeting, to be held in person.

 

Using probiotics to support digestive health for dogs

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

Because dogs are considered to be members of the family by most pet owners today, their health and well-being is a top priority. As with humans, nutritional products supporting gastrointestinal health are some of the most popular. Many pets are healthy, but loose stools, constipation, and various gastrointestinal disorders and diseases such as inflammatory bowel disease and irritable bowel syndrome are common. In fact, within the pet food conversation, digestive health improvements have been the most discussed health benefits among social media discussion posts over the past 2 years (see here). Given the high interest in digestive health, it is not surprising that the canine microbiome has been of great interest over the past decade, with many recent reviews reporting on the overall composition of the gastrointestinal microbiota and how it is impacted by diet (Barko et al., 2018; Alessandri et al., 2020; Wernimont et al., 2020). Gastrointestinal microbiome changes contributing to or resulting from digestive diseases have also been documented in dogs (Redfern et al., 2017; Ziese and Suchodolski, 2021). Animals under high levels of stress or undergoing antibiotic therapy are also known to have poor stool quality and an altered gut microbiota (i.e., dysbiosis) (Pilla et al., 2020).

Dietary fibers and prebiotics are commonly used in complete and balanced diets to improve or maintain stool quality, provide laxation, and positively manipulate the microbiota of healthy animals. The use of probiotics is also popular in dogs, but the route of administration, efficacy, and reason for use is usually different than that of fiber and prebiotics. Probiotics are usually provided in the form of supplements (e.g., powders, capsules, pastes) and are most commonly used to treat animals with gastrointestinal disease rather than support the healthy condition. Live microbes are added to many dry extruded foods as ‘probiotics’, but in many cases, maintaining viability and evidence for a health benefit for dogs is lacking for these products. Such microbes would not meet the minimum criteria to be called a ‘probiotic.’ Viability is a challenge because most HACCP plans for producing complete and balanced pet foods include a kill step that inactivates all microorganisms. Therefore, inclusion must be applied post-extrusion on the outside of the kibble. Even if applied in this way, low numbers of viable organisms are common (Weese and Arroyo, 2003). Post-production inclusion is not possible for other diet formats (e.g., cans, pouches, trays). Although spore-forming bacteria that may survive the extrusion process have been of interest lately, evidence of efficacy is lacking thus far.

Picture of Simka (a Samoyed) courtesy of ISAPP board member Dr. Daniel Tancredi

Even though health benefits coming from the inclusion of live microorganisms in dog foods is not supported by the peer-reviewed literature, such evidence exists for many probiotic supplements. The clinical effects of probiotics in the prevention or treatment of gastrointestinal diseases in dogs have been reviewed recently (Schmitz and Suchodolski, 2016; Suchodolski and Jergens, 2016; Jensen and Bjornvad, 2018; Schmitz, 2021). Although some similarities exist, recent research has shown that distinct dysbiosis networks exist in dogs compared to humans (Vazquez-Baeza et al., 2016), justifying unique prevention and/or treatment strategies for dogs.

One population of dogs shown to benefit from probiotics has been those with acute idiopathic diarrhea and gastroenteritis, with a shorter time to resolution and reduced percentage of dogs requiring antibiotic administration being reported (Kelley et al., 2009; Herstad et al., 2010; Nixon et al., 2019). Probiotic administration has also been shown to benefit dogs undergoing antibiotic therapy and those engaged in endurance exercise – two conditions that alter the gastrointestinal microbiota and often lead to loose stools. In those studies, consumption of a probiotic helped to minimize gastrointestinal microbiome shifts and reduced the incidence and/or shortened the length of diarrhea (Gagne et al., 2013; Fenimore et al., 2017). Dogs diagnosed with inflammatory bowel disease have also been shown to benefit from probiotic consumption (Rossi et al., 2014; White et al., 2017). In these chronic conditions, drug therapy is almost always required, but probiotics have been shown to help normalize intestinal dysbiosis, increase tight junction protein expression, and reduce clinical and histological scores.

So what is the bottom line? Well, for dogs with a sensitive stomach and/or digestive health issues, probiotics may certainly help. Rather than relying on live microbes present in the dog’s food or adding a couple spoonfuls of yogurt to the food bowl each day, it is recommended that owners work with their veterinarian to identify a probiotic that has the best chance for success. The probiotic selected should provide an effective dose, be designed for dogs, target the specific condition in mind, and be backed by science. As summarized here, it is important to remember that all probiotics are different so the specific microorganism(s), supplement form, storage conditions, and dosage are all important details to consider.

 

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.

ISAPP board member Prof. Dan Tancredi kindly provided pictures of Simka, pet Samoyed, for the post.

 

Follow up from ISAPP webinar – Probiotics, prebiotics, synbiotics, postbiotics and fermented foods: how to implement ISAPP consensus definitions

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

On the heels of the most recent ISAPP consensus paper – this one on postbiotics – ISAPP sponsored a webinar for industry members titled Probiotics, prebiotics, synbiotics, postbiotics and fermented foods: how to implement ISAPP consensus definitions. This webinar featured short presentations outlining definitions and key attributes of these five substances. Ample time remained for the 10 ISAPP board members to field questions from attendees.

When considering the definitions, it’s important to remember that the definition is a starting point – not all criteria can be included. Using the probiotic definition as an example, Prof. Colin Hill noted that the definition is only 15 words – Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. This is a useful definition, stipulating the core characteristics of a probiotic. However, important criteria such as safety and identity are not specified in the definition yet are clearly delineated in the full paper on probiotics.

Several interesting topics emerged from this discussion, which will be explored in future blog posts. These include:

  • What is meant by host health? Microbe mediated benefits are numerous. But not all benefits are a benefit to host health. Benefits for user appearance, pets and potentially livestock may be measurable, economically important and desirable, but may not encompass ‘host health’.
  • What types of endpoints are appropriate for studies to meet the requirement of a health benefit? Endpoints that indicate improved health (such as symptom alleviation, reduced incidence of infections or quality of life measures) are targeted. Some physiological measures that may be linked to health (such as increased fecal short chain fatty acids or changes in microbiota composition) may not be sufficient.
  • What are the regulatory implications from these definitions? As suggested by the National Law Review article on the ISAPP consensus definitions, attorneys are interested in the scientific positions on how these terms are defined and characterized. Further, some regulatory actions – such as by Codex Alimentarius in defining probiotics – are underway. ISAPP is open to suggestions about the best way to communicate these definitions to regulators.
  • Is any follow-up by ISAPP to these papers anticipated in order to clarify criteria and provide simple guidance to their implementation?

Simple guidance to these substances can be found in the infographics: probiotics, probiotic criteria, prebiotics, fermented foodshow are probiotic foods and fermented foods different, synbiotics, and postbiotics. As mentioned above, watch for blog updates on implementation of the definitions for different stakeholder groups.

The recording of this webinar is available here under password protection for ISAPP industry members only.

Related information:

Consensus panel papers, all published in Nature Reviews Gastroenterology and Hepatology:

A roundup of the ISAPP consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods

 

 

 

 

ISAPP thanks Prof. Glenn Gibson as he retires from the organization’s board of directors

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

Glenn Gibson – co-founder and backbone of ISAPP for over 20 years – has retired from the ISAPP board of directors.

In 1999, Glenn, Irene Lenoir-Wijnkoop and I conceived of ISAPP as a scientific ‘home’ for the multidisciplinary scientists involved in probiotic and prebiotic research. In 2002, ISAPP was incorporated as a non-profit, public service organization.

Colin Hill and Glenn Gibson

Through all the years, Glenn supported ISAPP beyond measure. His scientific acumen led to many insightful ideas for discussion groups and scientific speakers. He brought ISAPP and probiotic / prebiotic science to the attention of UK political strategists. He hosted meetings, chaired panels, authored publications, provided steady guidance and leadership, and helped keep the board focused on the mission at hand. He also promptly answered my interminable shower of emails for 20+ years. Highlights of his service include:

  • Co-founded ISAPP in 1999
  • Served as Vice President, President and Past President
  • Hosted ISAPP’s 2003 meeting in Henley, UK and 2007 in London, UK
  • Chaired 12 discussion groups
  • Chaired 2 ISAPP consensus panels, on probiotics (2013) and prebiotics (2016)
  • Co-authored 18 ISAPP publications (https://isappscience.org/publications/)
  • Chaired the innovative Springboard session at the Antwerp meeting (2019)
  • And so much more!

Glenn Gibson, Gregor Reid, Mary Ellen Sanders

What is more difficult to catalogue is how thoroughly enjoyable Glenn was to work with over the years. He did so much with an air of ease and joy, making it fun for everyone around him.

Glenn also masterfully decoupled ego from accomplishments. A person less dedicated to this principle would have reminded us ‘early and often’ (as they say) of his scientific stature in the field. Glenn remained approachable despite being one of the ‘greats’ – he started the field of prebiotics, a term addressed in over 9000 papers (close to 200 being his), and coined ‘synbiotics’, a term with 1700 papers currently published. I marvel at how many researchers and companies these two ideas have kept busy over the past 30 years. He developed a validated in vitro gut model, enabling mechanistic studies of the effects of dietary ingredients on gut microbiota, while conducting over 50 human studies, showing his commitment to move the science into the human so we can understand how it can make a difference in people’s lives. Yet still, his penchant was always to give others the credit, the limelight, the microphone, the opportunities.

His incredible stature in the field could have led him to dedicate his precious time to organizations much better established than ISAPP. But to the benefit of all of us, he was ISAPP’s greatest champion. His commitment radiated out to many academic experts who thought hey, if Glenn is in, I’ll be in, too, and to many industry scientists who simply relished the opportunity to network and collaborate with him under the ‘ISAPP umbrella’.

Gabriel Vinderola and Glenn Gibson, Singapore, 2018

Glenn believes that the right thing to do now is let ISAPP move into its next phase as he retires from board membership. I’ll be following his example in 3 years. Meanwhile, my challenge is to figure out how to find opportunities to keep him connected to the busy and dynamic ISAPP community.

As Glenn steps away, ISAPP would like to honor him by naming the Early Career Researcher Prize, which Glenn initiated, after him. The 2022 edition of the prize will be called the Glenn Gibson Early Career Researcher Prize. It’s a small gesture, as it’s impossible to thank Glenn sufficiently for all he has done for the ISAPP community. But we know he will continue to inspire the next generation of probiotic and prebiotic researchers! As his dedicated colleagues and friends, we wish him all the best as he brings his formidable talents to bear on other projects in the months and years ahead.

Enjoy this candid interview with Glenn.

 

A roundup of the ISAPP consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods

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

ISAPP has long recognized the importance of precise definitions of the ‘biotic’ family of terms. As a scientific organization working to advance global knowledge about probiotics, prebiotics, synbiotics, postbiotics and fermented foods, we believe carrying out rigorous scientific studies—and comparing one result to another—is more difficult if we do not start with a clear definition of what we are studying.

Over the past 8 years, ISAPP has endeavored to bring clarity to these definitions for scientists and other stakeholders. ISAPP board members have met with other top experts representing multiple perspectives and specialties in the field to develop precise, useful and appropriate definitions of the terms probiotics, prebiotics, synbiotics, postbiotics and fermented foods. The definitions of these first four terms have all entailed the requirement that the substance be shown to confer a health benefit in the target host. Fermented foods have multitudes of sensorial, nutritional and technological benefits, which drive their utility. A health benefit is not required.

The problem with health benefits

The definitions provide significant advantages for the scientific community in terms of clarity but complexity arises when the same definitions are accepted by regulatory agencies. This requirement for a health benefit as part of the probiotic definition has been rigorously implemented in the European Union. Currently, with the exception of a few member states, the term probiotic is prohibited. The logic is that since a health benefit is inherent to the term probiotic and since there are no approved health claims for probiotics in the EU*, the term ‘probiotic’ is seen to be acting as a proxy for a health claim. This has frustrated probiotic product companies who believe they have met the scientific criteria for probiotics, yet cannot identify their product as a probiotic in the marketplace because they have not received endorsement of their claims by the EU. This is not an issue resulting from an unclear definition, since probiotics surely should provide a health benefit, but rather from a lack of agreement as to what level of evidence is sufficient to substantiate a health benefit.

ISAPP remains committed to the importance of requiring a health benefit for the ‘biotic’ family of terms (outlined in the table below). It’s clear that all of these definitions are meaningless unless the requirement that they confer a health benefit is considered as essential by all stakeholders. One could reasonably discuss whether the required levels of evidence for foods and supplements are too high in some regulatory jurisdictions, but the value of these substances collapses in the absence of a health benefit.

Summary of ISAPP consensus definitions

With the publication of the most recent ISAPP consensus paper, this one on postbiotics, I offer a summary below of the five consensus definitions published by ISAPP. Each definition is part of a comprehensive paper resulting from focused discussions among experts in the field and published in Nature Reviews Gastroenterology and Hepatology (NRGH). These papers are among the top most viewed of all time on the NRGH website and are increasingly cited by scientists and regulators.

Table. Summary of ISAPP Consensus Definitions of the ‘Biotics’ Family of Substances. Probiotics, prebiotics, synbiotics and postbiotics have in common the requirement for a health benefit. They may apply to any target host, any regulatory category and must be safe for their intended use. Fermented foods fall only under the foods category and no health benefit is required.

Definition Key features of the definition Reference
Probiotics Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Grammatical correction of the 2001 FAO/WHO definition.

No mechanism is stipulated by the definition.

 

Hill et al. 2014
Prebiotics A substrate that is selectively utilized by host microorganisms conferring a health benefit Prebiotics are distinct from fiber. Beneficial impact on resident microbiota and demonstration of health benefit required in same study. Gibson et al. 2017
Synbiotics A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host Two types of synbiotics defined: complementary and synergistic. Complementary synbiotics comprise probiotic(s) plus prebiotic(s), meeting requirements for criteria for each. Synergistic synbiotics comprise substrate(s) selectively utilized by co-administered live microbe(s), but independently, the components do not have to meet criteria for prebiotic or probiotic. Swanson et al. 2020
Postbiotics Preparation of inanimate microorganisms and/or their components that confers a health benefit on the host Postbiotics are prepared from live microbes that undergo inactivation and the cells or cellular structures must be retained. Filtrates or isolated components from the growth of live microbes are not postbiotics. A probiotic that is killed is not automatically a postbiotic; the preparation must be shown to confer a health benefit, as well as meet all other criteria for a postbiotic. Salminen et al. 2021
Fermented Foods Foods made through desired microbial growth and enzymatic conversions of food components Fermented foods are not the same as probiotics. They are not required to have live microbes characterized to the strain level nor have evidence of a health benefit. Types of fermented foods are many and are specific to geographic regions. Compared to the raw foods they are made from, they may have improved taste, digestibility, safety, and nutritional value. Marco et al. 2021

 

 

*Actually, there is one approved health claim in the EU for a probiotic: Scientific Opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

 

Further reading: Defining emerging ‘biotics’

ISAPP publishes continuing education course for dietitians

For dietitians, it’s often difficult to find practical, up-to-date resources with a scientific perspective on probiotics, prebiotics, synbiotics and fermented foods. ISAPP is pleased to announce a new resource to fill this need – a Special Continuing Education Supplement in Today’s Dietitian titled, “Evidence-based use of probiotics, prebiotics and fermented foods for digestive health”. This free continuing education course also includes infographic summaries, links to supplementary information, and even some favourite recipes. US dietitians can earn 2.0 CPEUs for completing this self-study activity.

The resource was written by dietitian and assistant professor Dr. Hannah D. Holscher, along with two ISAPP board members, Prof. Robert Hutkins, a fermented foods and prebiotics expert, and Dr. Mary Ellen Sanders, a probiotic expert.

“We hope this course will give dietitians an overview of the evidence that exists for probiotics, prebiotics, synbiotics and fermented foods, and help explain some of the practical nuances around incorporating them into their practice,” says Sanders. “In addition, we believe that this course will be a scientifically accurate overview that can counter prevalent misinformation. It can serve as a useful resource for diverse array of professionals active in this field.”

Find the supplement here.

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

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

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

Dr. Mary Ellen Sanders: Probiotics and fermented foods

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

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

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

Prof. Glenn Gibson: Prebiotics and Synbiotics

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

Prof. Hania Szajewska, MD: Biotics for pediatric use

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

Prof. Gabriel Vinderola: Postbiotics

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

See here for the entire presentation on Biotics for Health.

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

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

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

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

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

Q&A (@1:20:00)

 

Five things scientists should know about the future of probiotics and prebiotics

By Marla Cunningham​, Metagenics Global R&D Innovation Manager and 2021 ISAPP Industry Advisory Committee representative

As anyone connected with probiotics and prebiotics knows – there’s a lot happening in this space.

After a well-attended discussion group at the 2019 ISAPP Annual Meeting in Antwerp, a collaboration of 16 industry and academic scientists came together to produce a broad overview of current and emerging trends that were covered in this discussion. Just released online by Trends in Microbiology, the open access paper identifies some top trends across multiple spheres of influence on the future of probiotics and prebiotics.

  1. Discovery: Prebiotics and probiotics are emerging from unexpected sources – naturally occurring as well as synthesised or engineered. Food, human and animal microbiome-derived probiotics feature heavily in probiotic development through top-down microbiome data-driven approaches as well as physiological target-driven screening approaches. Prebiotic sources have expanded beyond traditional plant sources to include food waste streams, animal gut-derived glycans and mammalian milk as well as increasingly sophisticated synthesis techniques, involving sonication, high pressure, acid, enzyme and oxidation treatments. A growing understanding of the implications of carbohydrate structure on microbial metabolism is driving the emergence of designer prebiotics, as specific substrates for microbes of interest or the production of target metabolites, such as polyphenol-derived bioactives.
  2. Evaluation: Calls for integrated systems biology -omic approaches to the evaluation of probiotic and prebiotics effects continue to increase, utilising whole genome and metabolite approaches, with a focus on better understanding of mode of action as well as differential host and microbial responses that serve to improve host health.
  3. Product development: Quality assurance techniques continue to undergo evolution as the challenges of divergent product formats and increasingly complex formulations necessitate innovation in the field. There is a focus on techniques beyond cell culture enumeration for probiotic product verification as well as on the identification of functional markers of probiotic and prebiotic activity, which can be applied in complex food matrices.
  4. Regulation: Recent regulatory challenges with claim approval are understood to have driven corresponding evolution in clinical science and an increased focus on mechanistic elucidation. However, the converse is also occurring, with the development of novel probiotic species, therapeutics for disease treatment and increasingly microbiome-driven modes of action having implications for regulatory frameworks. This ‘give and take’ between science and regulatory requirements will likely accelerate into the future as the field continues to evolve.
  5. Implementation: Interest continues to grow in precision and personalised approaches to nutrition and healthcare, especially in the field of microbiome-related interventions where there is significant appreciation of host-to-host variability. The identification of putative microbial signatures of health and disease continues to fuel the development of health-associated microbes as candidate probiotics and as targets for novel prebiotic substrates. Further, a focus beyond microbial composition and into microbial function is driving interest in interventions which can correct metabolomic profiles, such as probiotics with specific enzyme activity to boost synthesis or catabolism of key microbial metabolites in vivo, including purine and monoamine compounds.

These and other trends create a rich and evolving landscape for scientists within the field and provide the promise of a bright future for prebiotics and probiotics.

Read the full paper here

Reference:

Cunningham, M., Azcarate-Peril, M. A., Barnard, A., Benoit, V., Grimaldi, R., Guyonnet, D., Holscher, H. D., Hunter, K., Manurung, S., Obis, D., Petrova, M. I., Steinert, R. E., Swanson, K. S., van Sinderen, D., Vulevic, J., & Gibson, G. R. (2021). Shaping the Future of Probiotics and Prebiotics. Trends in microbiology, S0966-842X(21)00005-6. Advance online publication. https://doi.org/10.1016/j.tim.2021.01.003

 

 

 

Precision approaches to microbiota modulation: Using specific fiber structures to direct the gut microbial ecosystem for better health

By now, hundreds of scientific articles show the differences in gut microbiota composition and function between states of health and disease, leading to the idea that gut microbiota modulation is a promising way to achieve better health. But in practice, changing the complex community of microbes in the gut has proved challenging—the gut microbiota of the average adult is remarkably stable.

When it comes to diet, non-digestible carbohydrates are the main way to provide nutritional support to microbial populations and to modulate these communities, either in composition or in function. Can these dietary fibers be used to modulate the gut microbiota in a precise manner, with the aim of inducing certain health effects?

Prof. Jens Walter of APC Microbiome Ireland addressed this topic in a plenary lecture at the ISAPP 2020 annual meeting, titled: Precision microbiome modulation through discrete chemical carbohydrate structures.

Walter sees the gut microbiota as an complex ecological community of interacting microbes that is remarkably stable in healthy adults (albeit with a high degree of inter-individual variation). In order to precisely modulate gut microbiomes through diet, scientists must consider the ecological principles that shape these communities and determine how they function.

In the lecture, Walter introduced a perspective for using discrete fiber substrates to precisely modulate gut microbiota – a framework first articulated in a 2014 paper by Hamaker and Tuncil. According to this framework, gut microbiomes can be precisely manipulated, whether to achieve a certain microbiota composition or the production of health-relevant metabolites, through the use of specific fiber structures that are aligned with microbes that have the ability to utilize them. Walter explains some of the main challenges of the framework, which relate to the vast inter-individual differences in the gut microbes that are present, and their response to fiber; and discovering the exact dose of a fiber required for reliable changes in a person’s gut microbiota.

At the core of the presentation is a study by the Walter Lab that systematically tested the framework through a human dose-response trial using resistant starches with slight differences in their chemical structure. The findings of the study, which were published this year, illustrate how this ecological concept can be successfully applied. This shows the colonic microbiota can be successfully shaped in a desired manner with discrete dietary fiber structures.

See Prof. Walter’s presentation in full here.

New publication co-authored by ISAPP board members gives an overview of probiotics, prebiotics, synbiotics, and postbiotics in infant formula

For meeting the nutritional needs of infants and supporting early development, human milk is the ideal food—and this is reflected in breastfeeding guidelines around the world, including the World Health Organization’s recommendation that babies receive human milk exclusively for the first six months of life and that breastfeeding be continued, along with complementary foods, up to two years of age or beyond. In certain cases, however, breastfeeding is challenging or may not even be an option. Then, parents rely on alternatives for feeding their infants.

A group of scientists, including three ISAPP board members, recently co-authored an article in the journal Nutrients entitled Infant Formula Supplemented with Biotics: Current Knowledge and Future Perspectives. In the review, they aimed to highlight the new technologies and ingredients that are allowing infant formula to better approximate the composition of human milk. They focused on four types of ingredients: probiotics, prebiotics, synbiotics, and postbiotics.

Co-author Gabriel Vinderola, Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL) in Santa Fe, Argentina says, “Modern technologies have allowed the production of specific microbes, subtrates selectively used by the host microbes, and even non-viable microbes and their metabolites and cell fragments—for which scientific evidence is available on their effects on infant health, when administered in adequate amounts. Thus, this current set of gut modulators can be delivered by infant formula when breastfeeding is limited or when it is not an option.”

The authors say a well-functioning gut microbiota is essential for the overall health and proper development of the infant, and components of human milk support the development of this microbiota. They list important human milk components and the novel ingredients that aim to mimic the functions of these components in infant formulas:

  • Human milk oligosaccharides (HMOs)

HMOs are specialized complex carbohydrates found in human milk, which are digested in the infant colon and serve as substrates for beneficial microbes, mainly bifidobacteria, residing there. In recent years, prebiotic mixtures of oligosaccharides (e.g. short-chain GOS and long-chain FOS) have been added to infant formula to recapitulate the effects of HMOs. But now that it’s possible to produce several types of HMOs synthetically, some infant formulas are enriched with purified HMOs: 2’-fucosyllactose (2’FL) or lacto-N-neotetraose (LNnT). Even 3′-galactosyllactose (3′-GL) can be naturally produced by a fermentation process in certain infant formulas.

  • Human milk microbiota

Human milk has a complex microbiota, which is an important source of beneficial bacteria to the infant. Studies support the notion that the human milk microbiota delivers bioactive components that support the development of the infant’s immune system. Probiotic strains are sometimes added to infant formula in order to substitute for important members of the milk microbiota.

  • Bacterial metabolites

Human milk also contains metabolic byproducts of bacteria called “metabolites” in addition to the bacteria themselves. These components have not been fully studied to date, but bacterial metabolites such as butyrate and other short-chain fatty acids may have important health effects for the overall development of the infant. A future area of nutritional research is likely to be the addition of ‘postbiotics’ — non-viable cells, their metabolites and cell components that, when administered in adequate amounts, promote health and well-being — to infant formulas. (ISAPP convened a scientific consensus panel on the definition of postbiotics, with publication of this definition expected by the end of 2020.)

 

The precise short- and long-term health benefits of adding the above ingredients to infant formula are still under study. One pediatric society (the ESPGHAN Committee on Nutrition) examined the data in 2011 and at that time did not recommend the routine use of infant formulas with added probiotic and/or prebiotic components until further trials were conducted. A systematic review concluded that evidence for the health benefits of fermented infant formula (compared with standard infant formula) are unclear, although improvements in infant gastrointestinal symptoms cannot be ruled out. Although infant formulas are undoubtedly improving, review co-author Hania Szajewska, MD, Professor of Paediatrics at The Medical University of Warsaw, Poland, says, “Matching human milk is challenging. Any alternative should not only match human milk composition, but should also match breastfeeding performance, including how it affects infant growth rate and other functions, such as the immune response.”

 

Can the microbiota help protect against viral infections? Summary of an ISAPP discussion group

By Drs. Karen Scott, University of Aberdeen, and Sarah Lebeer, University of Antwerp

As part of the ISAPP virtual annual meeting 2020, around 85 members of the ISAPP community joined us in a Zoom discussion forum to discuss the topic: “Do our resident microbes help protect against viral infections?” A scientific perspective on this topic is especially important during the COVID-19 pandemic, when many members of the general public are wondering about actions (if any) they can take to protect themselves before a SARS-CoV-2 vaccine becomes widely available.

We introduced the topic and were joined by several invited experts, who also gave short presentations:

  • Joel Dore (INRAE France)
  • Tine Licht (Technical University of Denmark)
  • Mary O’Connell-Motherway (APC Microbiome, Cork)

The ensuing conversation, open to all participants, was wide-ranging, starting with the gut microbiota and expanding to include the microbiota at other body sites, and the effects of the gut microbiota around the body gut via transport of metabolites. Here are some of the main take-home messages from this discussion.

Components of the microbiota (bacteria, fungi, archaea, viruses and others) at a body site interact with each other. Although scientists often study one component of the (gut) microbiota at a time, members of the microbiota from different kingdoms interact with each other in ways that can be positive or negative for the host. In particular, specific activities of bacteria can be widespread, frequent or rare among members of the microbiota – and it is often the rare activities that have important impacts on the course of a disease: e.g. specific antimicrobial agents produced by some bacteria prevent Salmonella infections in pigs and cure mastitis in cows.

Mechanistic work shows bacteria in the microbiota can prevent, eliminate or promote viral infections. Studies have shown some microbes can prevent attachment of viruses to cell surfaces by offering alternative receptors. In contrast, virus particles can utilise other bacterial cells to “mask” them and facilitate entry into host cells. Other bacteria can stimulate the immune system to promote elimination of a viral infection, while under specific circumstances this same immune activation may promote viral infection. When it comes to the microbiota of the respiratory tract, studies have shown its bacterial members play a crucial defensive role. Probiotics that are already shown to be effective against other viral upper respiratory tract infections may have promise for COVID-19 (either for preventing infection or enhancing recovery), and currently studies are underway to investigate these.

Probiotics or prebiotics could be useful adjuncts to vaccination, but they are not likely to become a reality for COVID-19. Scientists are perennially interested in the topic of vaccine efficacy, and some probiotics have been shown to increase efficacy for widely available vaccines in certain populations. But in the current pandemic, developing a safe and effective vaccine (or vaccines) is the primary concern. Testing the possibility of probiotic or prebiotic combination therapies would be secondary, since the necessary testing would take longer in order to evaluate the adjuvant potential of different probiotic strains. Because the expression of cell surface molecules that can mediate adjuvant activity is strain-dependent, screening and selecting the best strains would probably take too long to become a reality for COVID-19. Certainly, participants agreed that introduction of a safe, effective vaccine was the priority, without any delays to test out ‘extras’.

A scientific rationale exists for maintaining gut microbiota diversity in order to reduce the development of diseases which, as “underlying health conditions”, may result in more severe COVID-19 outcomes. It is clear that individuals with certain underlying health conditions—related to the central nervous system and gastrointestinal system, and to metabolic and immunological dysfunction—tend to experience a more severe disease, with worse outcomes, following SARS-CoV-2 infection. Many of these conditions are also associated with a gut microbiota that is different from that of healthy controls. Research consistently shows that individuals with metabolic disease, for example, have a less diverse, lower ‘richness’ microbiota, which is often linked to increased intestinal permeability, higher gut inflammation and more oxidative stress throughout the body. This increased oxidative stress then exacerbates the microbial dysbiosis, causing more inflammation and increased intestinal permeability – creating a vicious cycle effect. This cycle is linked with obesity and metabolic disorders. In healthy individuals who are at risk of developing such conditions, the diversity of the existing resident microbiota may be increased by the application of prebiotics or synbiotics, included within a healthy, diverse, high-fibre diet. These approaches may improve bacterial fermentation in the large intestine, resulting in increased production of important bacterial metabolites that help regulate host metabolism, including short-chain fatty acids.

Until a SARS-CoV-2 vaccine is available, supporting a diverse and complex gut microbiota through diet may contribute to maintaining health in at-risk populations. Despite the intense worldwide scientific efforts and collaborations, it is unlikely that an effective vaccine against COVID-19 will be widely available soon. In the meantime, we have to protect ourselves and our local ‘at-risk’ populations as best we can. We are learning more and more about the mechanisms of dietary fibre’s health effects, in which gut bacteria play a major role. Evidence suggests that keeping our gut microbiota as complex and diverse as possible by consuming a high-fibre diet (supplemented by fermented foods, probiotics and prebiotics) might help mitigate susceptibility to infections in general.

New synbiotic definition lays the groundwork for continued scientific progress

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

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

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

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

A diverse panel of experts

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

An inclusive definition

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

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

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

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

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

Implications for study design

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

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

Continuing scientific progress

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

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

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

Find the ISAPP press release on this publication here.

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

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

ISAPP Conference Session

New Probiotic and Prebiotic Society Among Ibero-American Countries

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

On February 8, 2019, within the framework of the X Workshop of the Spanish Society for Microbiota, Probiotics and Prebiotics (SEMiPyP), the Ibero-American Society for Microbiota, Probiotics and Prebiotics (SIAMPyP) was established, with the aim of enhancing communication among researchers and clinicians from Spain, Portugal, Mexico and several South American countries.

SIAMPyP will build on 10 years of collaboration among experts from both sides of the Atlantic, who have come together as SEMiPyP with a common interest in the potential of the microbiome in human health and disease, in promoting and disseminating scientific discovery, in rigor of scientific evidence, and facilitating future research to the benefit of Ibero-America and the globe.

Currently, the plan is for SIAMPyP to convene biennial meetings, the first being planned for March 2021 (dependent on the state of the pandemic) in Madrid and subsequently in 2023 in Mexico City.  Academic sessions of basic and clinical science will be presented in this context, taking advantage of common languages (Spanish and Portuguese) to establish synergies in Latin American countries and the Iberian Peninsula.

The SIAMPyP has fostered connections with other international academic and scientific societies with knowledge in microbiota, probiotics and prebiotics in the pediatric, gastroenterology and neurogastroenterology fields of various Spanish and Portuguese speaking countries, as well as with ISAPP. Likewise, it has the support of research-oriented pharmaceutical and food industries that seek to modulate the microbiota to benefit human health in various clinical settings with probiotics, prebiotics and postbiotics.

The current board of directors of SIAMPYP is chaired and represented by doctors from both continents, including the well-known scientists Dr. Francisco Guarner (former ISAPP board member, from Spain), Dr. Guiilermo Alvarez-Calatayud (Spain), Dr. Luis Peña (Spain), as well as Dr. Aldo Maruy (Peru), Dr. Christian Boggio (Argentina) and Dr. Ana Teresa Abreu (Mexico), in addition to members and consultants who support and strengthen it, divided by region, with Latin America being a region with several countries.

SIAMPyP welcomes scientific partners from all Ibero-American countries, at no cost. See www.siampyp.org for further information.

Hear from ISAPP board members in webinar covering probiotic and prebiotic mechanisms of action

This webinar is now complete — see the recorded version here.

New probiotic and prebiotic trials are published all the time – but when they show a health benefit, what do we know about the basic science behind it?

To provide insight into this topic, ISAPP has partnered with the International Life Sciences Institute (ILSI) Europe on a free webinar titled Understanding Prebiotic and Probiotic Mechanisms that Drive Health Benefits. This webinar helps scientists, members of the public, and media take a deep dive into what we know about the mechanisms of action of probiotics and prebiotics.

The live webinar is scheduled for Thursday, September 17, 2020 from 3 – 4:15pm Central European Time.

Short, 10-minute perspectives will be provided by the following top experts:

  • Prof. Sarah Lebeer, University of Antwerp, Belgium
  • Prof. Colin Hill, University College Cork, Ireland
  • Prof. Karen Scott, University of Aberdeen, UK
  • Prof. Koen Venema NUTRIM School of Nutrition and Translational Research in Metabolism, Venlo, The Netherlands

The presentations will be followed by a 35-minute live Q&A session, enabling participants to probe deeper into the science behind mechanisms of probiotics and prebiotics.

ILSI Europe is a non-profit organization that aims to improve public health and well-being from a science-based approach.

To learn more about probiotic mechanisms of action in advance of the webinar, see ISAPP’s blog post here.

Early career researchers discuss the future of probiotics and prebiotics in the first ISAPP-SFA paper

By Irina Spacova, ISAPP-SFA 2019 President and postdoctoral fellow at the University of Antwerp, Belgium

Early career scientists play a vital and dynamic role in research, especially in environments supporting their enthusiasm and drive for innovation. ISAPP has long been promoting young researchers through its Students and Fellows Association (ISAPP-SFA), which is a student-led branch of ISAPP established in 2009. The SFA was championed and guided from its inception through June 2020 by Prof. Gregor Reid. Together with ISAPP, the organization encourages diversity and participation through free memberships and ISAPP meeting travel grants open to all students and fellows working in research institutions. Currently, ISAPP-SFA includes 450 members from 50 countries in Asia, Africa, North and South America, Europe, and Australia.

The 2019 ISAPP meeting in Antwerp, Belgium was a milestone for ISAPP-SFA participation with 48 early career attendees from 19 countries. Facilitated by discussion clubs and poster sessions, the Antwerp meeting created an exceptional ‘melting pot’ of ideas. It was clear that young researchers had a lot to say, and the lingering idea of creating the first ISAPP-SFA paper finally took shape during the ISAPP 2019 dinner cruise of the Antwerp Harbor.

Less than a year later, the paper “Future of probiotics and prebiotics and the implications for early career researchers” was accepted in Frontiers in Microbiology, just in time for the 2020 ISAPP meeting. This initiative was driven by the ISAPP-SFA 2019 executive committee members Irina Spacova, Hemraj Dodiya, Anna-Ursula Happel, Conall Strain, Dieter Vandenheuvel, and Xuedan Wang. The core of the paper reflects what we as early career researchers believe are the biggest opportunities and challenges in advancing probiotic and prebiotic science, and summarizes a wide array of promising in vitro, in vivo and in silico tools. We emphasize the important goal of using probiotics and prebiotics to ameliorate global issues, and give examples of current initiatives in developing countries, such as Westernheadseast.ca and Yoba4Life.org. Our advice for early career researchers is to form inter-connected teams and implement the diverse toolsets to further advance the probiotics and prebiotics field.

We had a lot of fun with this paper, but also several challenges. It was not trivial to produce a concise paper with many opinions, techniques and references that would be useful to both young and established researchers. This intercontinental endeavor between young scientists working in Belgium, Japan, Ireland, South Africa, USA, and UK required a lot of early-morning and late-night meetings. Many interactions and discussions were necessary to deliver a novel perspective to add to the many excellent reviews on probiotics and prebiotics already published. Accessibility of the publication was a decisive factor, and one of the reasons why we chose to publish open access in Frontiers in Microbiology. Of course, this publication would not be possible without ISAPP, and we are especially grateful for the input and encouragement from Gregor Reid and Mary Ellen Sanders.

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

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

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

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

Benefits of prebiotics for pets

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

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

Types of pet-friendly prebiotics

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

Which pets benefit most?

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

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

Further research on prebiotic substances

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

 

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

 

 

 

ISAPP welcomes three new board members

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

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

Read more about ISAPP’s newest board members:

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

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

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

 

ISAPP provides guidance on use of probiotics and prebiotics in time of COVID-19

By ISAPP board of directors

Summary: No probiotics or prebiotics have been shown to prevent or treat COVID-19 or inhibit the growth of SARSCoV-2. We recommend placebo-controlled trials be conducted, which have been undertaken by some research groups. If being used in clinical practice in advance of such evidence, we recommend a registry be organized to collect data on interventions and outcomes.  

Many people active in the probiotic and prebiotic fields have been approached regarding their recommendations for using these interventions in an attempt to prevent or treat COVID-19. Here, the ISAPP board of directors provides some basic facts on this topic.

What is known. Some human trials have shown that specific probiotics can reduce the incidence and duration of common upper respiratory tract infections, especially in children (Hao et al. 2015; Luoto et al. 2014), but also with some evidence for adults (King et al. 2014) and nursing home residents (Van Puyenbroeck et al. 2012; Wang et al. 2018). However, not all evidence is of high quality and more trials are needed to confirm these findings, as well as determine the optimal strain(s), dosing regimens, time and duration of intervention. Further, we do not know how relevant these studies are for COVID-19, as the outcomes are for probiotic impact on upper respiratory tract infections, whereas COVID-19 is also a lower respiratory tract infection and inflammatory disease.

There is less information on the use of prebiotics for addressing respiratory issues than there is for probiotics, as they are used mainly to improve gut health. However, there is evidence supporting the use of galactans and fructans in infant formulae to reduce upper respiratory infections (Shahramian et al. 2018; Arslanoglu et al. 2008). A meta-analysis of synbiotics also showed promise in repressing respiratory infections (Chan et al. 2020).

Mechanistic underpinnings. Is there scientific evidence to suggest that probiotics or prebiotics could impact SARS-CoV-2? Data are very limited. Some laboratory studies have suggested that certain probiotics have anti-viral effects including against other forms of coronavirus (Chai et al. 2013). Other studies indicate the potential to interfere with the main host receptor of the SARS-CoV-2 virus, the angiotensin converting enzyme 2 (ACE2). For example, during milk fermentation, some lactobacilli have been shown to release peptides with high affinity for ACE (Li et al. 2019). Recently, Paenibacillus bacteria were shown to naturally produce carboxypeptidases homologous to ACE2 in structure and function (Minato et al. 2020). In mice, intranasal inoculation of Limosilactobacillus reuteri (formerly Lactobacillus reuteri) F275 (ATCC 23272) has been shown to have protective effects against lethal infection from a pneumonia virus of mice (PVM) (Garcia-Crespo et al. 2013). These data point towards immunomodulatory effects involving rapid, transient neutrophil recruitment in association with proinflammatory mediators but not Th1 cytokines. A recent study demonstrated that TLR4 signaling was crucial for the effects of preventive intranasal treatment with probiotic Lacticaseibacillus rhamnosus (formerly Lactobacillus rhamnosus) GG in a neonatal mouse model of influenza infection (Kumova et al., 2019). Whether these or other immunomodulatory effects, following local or oral administration, could be relevant to SARS-CoV-2 infections in humans is at present not known.

Our immune systems have evolved to respond to continual exposure to live microbes. Belkaid and Hand (2016) state: “The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes.” This suggests a mechanism whereby exposure to dietary microbes, including probiotics, could positively impact immune function (Sugimura et al. 2015; Jespersen et al. 2015).

The role of the gut in COVID-19. Many COVID-19 patients present with gastrointestinal symptoms and also suffer from sepsis that may originate in the gut. This could be an important element in the development and outcome of the disease. Though results from studies vary, it is evident that gastrointestinal symptoms, loss of taste, and diarrhea, in particular, can be features of the infection and may occur in the absence of overt respiratory symptoms. There is a suggestion that gastrointestinal symptoms are associated with a more severe disease course. Angiotensin converting enzyme 2 and virus nucleocapsid protein have been detected in gastrointestinal epithelial cells, and infectious virus particles have been isolated from feces. In some patients, viral RNA may be detectable in feces when nasopharyngeal samples are negative. The significance of these findings in terms of disease transmission is unknown but, in theory, do provide an opportunity for microbiome-modulating interventions that may have anti-viral effects (Cheung et al. 2020; Tian et al. 2020; Han et al. 2020).

A preprint (not peer reviewed) has recently been released, titled ‘Gut microbiota may underlie the predisposition of healthy individuals to COVID-19’ (Gao et al. 2020) suggesting that this could be an interesting research direction and worthy of further discussion. A review of China National Health Commission and National Administration of Traditional Chinese Medicine guidelines also suggested probiotic use, although more work on specific strains is needed (Mak et al. 2020).

Are probiotics or prebiotics safe? Currently marketed probiotics and prebiotics are available primarily as foods and food/dietary supplements, not as drugs to treat or prevent disease. Assuming they are manufactured in a manner consistent with applicable regulations, they should be safe for the generally healthy population and can be consumed during this time.

Baud et al. (in press) presented a case for probiotics and prebiotics to be part of the management of COVID-19. Although not fully aligned with ISAPP’s official position, readers may find the points made and references cited of interest.

Conclusion. We reiterate, currently no probiotics or prebiotics have been shown to prevent or treat COVID-19 or inhibit the growth of SARSCoV-2.

 

Connecting with the ISAPP community: Continuing to advance the science of probiotics and prebiotics

By Mary Ellen Sanders PhD, executive science officer, ISAPP

On behalf of the ISAPP board of directors, I am reaching out to the ISAPP community to say we hope you are doing well and taking all the necessary steps in your local communities to remain healthy. At present, the global ISAPP community is physically distant but digitally close, and it is important for us to remain connected and strong.

ISAPP’s activities are as important as ever during this time of increased attention to health, and ISAPP is continuing to uphold its commitment to (1) stewardship, (2) advancing the science, and (3) working with stakeholders. Although our annual meeting, which some of you may have initially planned to attend, has been cancelled, other ISAPP activities are continuing or expanding as follows:

 

  • Building on an important topic for our annual meeting, ISAPP is working to develop a strategic approach to communicating the science on probiotics, prebiotics, fermented foods, synbiotics, and postbiotics.
  • The ISAPP board of directors is pleased that our founding board members, Profs. Gregor Reid and Glenn Gibson, have agreed to remain on the board until the 2021 meeting, in particular to help with long-range planning. New academic board members will also be elected, thereby expanding the board. Working together, we will bring fresh insights, strategies and global reach.
  • The board is considering how best to approach our cancelled meeting. In lieu of re-scheduling this year’s in-person meeting, we are planning to have virtual content covering some of the originally scheduled topics. Some discussion group topics will be carried over to the 2021 meeting, while others will be addressed virtually. We will communicate further on this soon.
  • Our newsletter will continue on a monthly basis.
  • Blog postings, which are aimed at either consumers or scientists, remain timely and popular – with new contributions posted on average every 2-3 weeks. Authored by board members and other experts in the field, these blogs provide a forum for opinions and observations on current issues and controversies as well as insights on global fermented foods, critical regulatory actions, and other relevant topics.
  • ISAPP filed comments on March 17 with the American Gastroenterological Association in response to their draft recommendations for probiotic use in GI conditions.
  • Spearheaded by former ISAPP IAC representative to the board, Dr. Roberta Grimaldi, ISAPP has subtitled several of the most popular ISAPP videos in different languages, including Dutch, French, Spanish, Russian, Japanese, Italian and Indonesian. The first of these should be posted by end of April.
  • The ISAPP-Students and Fellows Association has launched a blog program to provide perspectives by young scientists on issues of importance to the probiotic and prebiotic fields. They have also submitted a manuscript to Frontiers in Microbiology discussing a toolkit needed for their future in science: “Future of probiotics and prebiotics: an early career researchers’ perspective”.
  • Three consensus panels have been conducted since May of 2019. A manuscript arising from the synbiotics panel, chaired by Prof. Kelly Swanson, is in press with Nature Reviews Gastroenterology and Hepatology. The paper summarizing the consensus panel on fermented foods, chaired by Profs. Robert Hutkins and Maria Marco, is almost ready for submission to Nature Reviews Gastroenterology and Hepatology. A manuscript from the consensus panel on postbiotics, chaired by Prof. Seppo Salminen, is currently being written. All three papers are expected to provide clarity to the field with regard to definition of terms, current evidence for health benefits, and impact on stakeholders.
  • In addition to the three consensus panel papers in progress, several different ISAPP endeavors are at different stages of publication:
    • ISAPP vice president, Prof. Dan Merenstein, and executive science officer, Dr. Mary Ellen Sanders, worked with biostatistician and frequent ISAPP contributor, Prof. Dan Tancredi, to summarize evidence for clinical endpoints for probiotics, to be published in the Journal of Family Physicians. This paper, titled “Probiotics as a Tx resource in primary care”. The paper is currently in press.
    • Several ISAPP board members and other participants in a 2019 meeting discussion group recently submitted to Current Developments in Nutrition a paper titled “Dietary Recommendation on Adequate Intake of Live Microbes: A Path Forward”.
    • Marla Cunningham, the current IAC representative to the ISAPP board, has led an effort to compile results from the IAC Learning Forum from the 2019 ISAPP meeting on the topic of matrix effects impacting probiotic and prebiotic functionality. Manuscript in preparation.
    • Colin Hill and I represented ISAPP on a paper under review at Nutrients initiated by IPA-Europe titled “Criteria to qualify microorganisms as ‘probiotic’ in foods and dietary supplements”. This paper consolidates and fleshes out minimum criteria for use of the term ‘probiotic’ published by different groups, including the 2002 FAO/WHO working group, the 2014 ISAPP consensus paper on probiotics, and the 2018 ISAPP discussion group on global harmonization.
    • Glenn Gibson and Marla Cunningham are coordinating a paper titled “The future of probiotics and prebiotics in human health” as an output from their 2019 discussion group.

See here for all published ISAPP papers.

ISAPP board members, 2019 annual meeting

Messages about probiotics and COVID-19

With many conflicting and confusing health messages circulating during this global pandemic, including some criticisms of our field as well as some unsupported claims made by certain individuals and companies, ISAPP will remain an important touchstone for scientifically accurate information. Focusing on health effects is key to demonstrating probiotic and prebiotic efficacy, and we acknowledge that human studies are the ultimate measure of efficacy, but also, elucidating mechanisms of action help us understand how these interventions interface with the immune system and other mediators of health.  Currently, there is some evidence that certain probiotics/prebiotics can reduce the risk of viral infections (discussed in other blog posts here and here), but it is important to remember that they have not been studied specifically for COVID-19 prevention or treatment. This must be acknowledged when communicating with the wider community.

We greatly appreciate the continued support of our IAC members. The ISAPP Board, colleagues, and SFA will continue to chart a course forward in preparation for life after the pandemic. Our intent is to emerge from these experiences more connected and purposeful than ever. We welcome suggestions on how collectively we can endure and strengthen the science and communications that remain foundations of our field.