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Prebiotics do better than low FODMAPs diet

/in Consumer Blog, featured, ISAPP Science Blog /by ISAPP

By Francisco Guarner MD PhD, Consultant of Gastroenterology, Digestive System Research Unit, University Hospital Vall d’Hebron, Barcelona, Spain

Bloating and visible abdominal distention after meals is a frequent complaint of people suffering from irritable bowel syndrome, but even generally healthy people sometimes have these complaints. These symptoms are thought to be due to fermentation of food that escapes our digestive processes. Some sugars and oligosaccharides end up at the far end of our small bowel and cecum, where they become food for our resident microbes.

To manage this problem, medical organizations recommend antibiotics to suppress the microbial growth in our small intestine (known as small intestinal bacterial overgrowth or SIBO) or avoidance of foods that contain fermentable oligosaccharides, disaccharides, monosaccharides and polyols, called a low “FODMAP” diet. These approaches are generally successful in reducing symptoms, but do not provide permanent relief: symptoms typically return after the strategies are stopped.

Even worse, both approaches are known to disrupt the entire gut microbial ecosystem (not only at small bowel and cecum). Whereas a healthy microbial gut ecosystem has many different types of bacteria, antibiotics deplete them.  The low FODMAP diet deprives beneficial bacteria (such as Faecalibacterium, Roseburia, Bifidobacterium, Akkermansia, Lactobacillus and others) of the food they like to eat, and these species wane (see here).

Prof. Glenn Gibson, a founding father of prebiotic and synbiotic science, suggested that increasing ingestion of certain prebiotics could increase levels of bifidobacteria. These bifidobacteria in turn could prevent excessive gas production since they are not able to produce gas when fermenting sugars.  (Instead, bifidobacteria product short chain fatty acids, mainly lactate, which are subsequently converted to butyrate by other healthy types of bacteria, such as Faecalibacterium and Roseburia.)

Prof. Gibson’s hypothesis was tested in pilot studies where volunteers ingested a prebiotic known as galacto-oligosaccharide (Brand name: Bimuno). Healthy subjects were given 2.8 g/day of Bimuno for 3 weeks. At first, they had more gas: significantly higher number of daily anal gas evacuations than they had before taking the prebiotic (see here). The volume of gas evacuated after a test meal was also higher. However, after 3 weeks of taking the prebiotic, daily evacuations and volume of gas evacuated after the test meal returned to baseline. The microbe populations also started to recover. The relative abundance of healthy butyrate producers in fecal samples increased and correlated inversely with the volume of gas evacuated. This suggested that the prebiotic induced an adaptation of microbial metabolism, resulting in less gas.

Then researchers launched a second study, also in healthy volunteers, to look at how the metabolic activity of the microbiota changed after taking this prebiotic. They showed that adaptation to this prebiotic involves a shift in microbiota metabolism toward low-gas producing pathways (see here).

A third controlled study (randomized, parallel, double-blind), this time in patients with functional gastrointestinal disorders with flatulence, compared the effects of the prebiotic supplement (2.8 g/d Bimuno) plus a placebo diet (mediterranean-type diet) to a placebo supplement plus a diet low in FODMAPs. The study subjects were divided between these 2 diets, which they consumed for 4 weeks (see here). Both groups had statistically significant reductions in symptom scores during the 4-week intervention. Once subjects stopped taking the prebiotic, they still showed improved symptoms for 2 additional weeks (at this point, the study was completed). However, for subjects on the low-FODMAP diet, once the diet was stopped, symptoms reappeared. Very interestingly, these 2 diets had opposite effects on fecal microbiota composition. Bifidobacterium increased in the prebiotic group and decreased in the low-FODMAP group, whereas Bilophila wadsworthia (a sulfide producing species) decreased in the prebiotic group and increased in the low-FODMAP group.

The bottom line conclusion is that a diet including intermittent prebiotic administration might be an alternative to the low FODMAP diets that are currently recommended for people with functional gut symptoms, such as bloating and abdominal distention. Since low FOD MAP diets are low in fiber, the prebiotic option may provide a healthier dietary option.

 

  1. Halmos EP, Christophersen CT, Bird AR, Shepherd SJ, Gibson PR, Muir JG. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64(1):93–100.
  2. Mego M, Manichanh C, Accarino A, Campos D, Pozuelo M, Varela E, et al. Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study. Aliment Pharmacol Ther. 2017;45(5):670–80.
  3. Mego M, Accarino A, Tzortzis G, Vulevic J, Gibson G, Guarner F, et al. Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans. Neurogastroenterol Motil. 2017;29(9):e13080.
  4. Huaman J-W, Mego M, Manichanh C, Cañellas N, Cañueto D, Segurola H, et al. Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders. Gastroenterology. 2018;155(4):1004-7.

 

Additional reading:

Halmos EP, Christophersen CT, Bird AR, Shepherd SJ, Gibson PR, Muir JG. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64(1):93–100.

Mego M, Manichanh C, Accarino A, Campos D, Pozuelo M, Varela E, et al. Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study. Aliment Pharmacol Ther. 2017;45(5):670–80.

Mego M, Accarino A, Tzortzis G, Vulevic J, Gibson G, Guarner F, et al. Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans. Neurogastroenterol Motil. 2017;29(9):e13080.

Huaman J-W, Mego M, Manichanh C, Cañellas N, Cañueto D, Segurola H, et al. Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders. Gastroenterology. 2018;155(4):1004-7.

Halmos EP, Gibson PR. Controversies and reality of the FODMAP diet for patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2019 Jul;34(7):1134-1142. doi: 10.1111/jgh.14650. Epub 2019 Apr 4.

 

 

new_website

ISAPP launches new website, furthering its mission of educating stakeholders on probiotic and prebiotic science

/in featured, News /by ISAPP

The ISAPP Board of Directors is pleased to announce the launch of the organization’s new website, which has now gone live at ISAPPscience.org. The website has been redesigned for easier navigation by different stakeholder groups—scientists, consumers, clinicians, and students—enabling ISAPP to continue with its mission of providing accurate, science-based information to its readers about probiotics, prebiotics and fermented foods.

ISAPP Executive Science Officer Dr. Mary Ellen Sanders says, “The scientists comprising the ISAPP Board of Directors realize that consumers and clinicians often struggle to find science-based information on probiotics and prebiotics. ISAPP is working to fill this gap, and we have streamlined our website to help individuals from each of these groups easily find the information they’re looking for.”

At the ISAPP annual meeting held earlier this year, advancing probiotic and prebiotic evidence to a variety of audiences was the topic of a special ‘springboard discussion’ session.

“Probiotic and prebiotic science has made significant progress in the past few decades,” says Sanders, “but this progress has not always been communicated effectively or correctly to those outside the scientific community.” Sanders continues, “Some studies describe an expanding array of health benefits but other studies show the limits of these interventions. Our goal is to counter the abundance of misinformation and be the go-to source of accurate materials about probiotics and prebiotics.”

ISAPP is building its capacity to produce more science-focused educational materials tailored to different audiences. Infographics, some of which are translated into 10 different languages, short videos and targeted blogs are featured on the new website. In coming weeks, ISAPP will make additional resources available on the website, including frequently asked questions about probiotics and prebiotics, and a downloadable white paper for clinicians. Signing up for the ISAPP newsletter is the best way to stay up to date on educational materials being added to the website.

ISAPP’s 2019 annual meeting in Antwerp, Belgium: Directions in probiotic & prebiotic innovation

/in featured, News /by ISAPP

Kristina Campbell, Microbiome science writer, Victoria, British Columbia

We live in a time when a simple Google search for ‘probiotics’ produces over 56.8 million hits; a time when almost everyone has heard of probiotics through one channel or another, and when an ever-increasing variety of probiotic and prebiotic products is available in different regions of the world.

The next five to ten years will be telling: will probiotics and prebiotics join the ranks of other trendy health products that experienced a wave of popularity before something else took their place? Or will they be recognized as important contributors to health through the lifespan, and establish a permanent position in the clinical armamentarium?

According to the global group of 175 academic and industry scientists who met for the ISAPP annual meeting in Antwerp (Belgium) May 14-16, 2019, one thing above all is necessary for the world to recognize the significance of probiotics and prebiotics for health: scientific innovation. Not only are technological capabilities advancing quickly, but also, new products are being evaluated by better-educated consumers who demand more transparency about the health benefits of their probiotics and prebiotics.

Participants in the ISAPP conference came together to talk about some of the leading innovations in the world of probiotics and prebiotics. Here are three of the broad themes that emerged:

Better health through the gut-brain axis

Gut-brain axis research is rapidly growing, with many investigators in search of probiotic and prebiotic substances capable of modulating brain function in meaningful ways. Phil Burnett of Oxford (UK) presented on “Prebiotics, brain function and stress: To what extent will prebiotics replace or complement drug therapy for mental health?”. Burnett approached the challenge by administering prebiotics to healthy adults and giving them a battery of psychological tests; in one experiment he found people who consumed a prebiotic (versus placebo) showed benefits that included reduced salivary cortisol and positively altered emotional bias. For those with diagnosed brain disorders, Burnett concludes from the available data that prebiotics have potential anxiolytic and pro-cognitive effects in these populations, and that prebiotics may eventually be used to complement the established treatments for some mental disorders.

Short-chain fatty acids (SCFAs) are of interest as potential modulators of brain function, but so far very little research has been carried out in this area. Kristin Verbeke of Leuven (Belgium) gave a talk entitled “Short-chain fatty acids as mediators of human health”, which covered the extent to which interventions with fermentable carbohydrates can alter systemic SCFA concentrations (rather than gut SCFA concentrations)—since the former are more relevant to effects on the brain.

Also, a students and fellows feature talk by Caitlin Cowan of Cork (Ireland) explored a role for the microbiota in psychological effects of early stress. She spoke on the topic “A probiotic formulation reverses the effects of maternal separation on neural circuits underpinning fear expression and extinction in infant rats”.

A clear definition of synbiotics

Immediately before the main ISAPP meeting, a group of experts met to propose a consensus definition of ‘synbiotic’, with the objective of clarifying for stakeholders a scientifically valid approach for the use of the increasingly-popular term. A key point of discussion was whether the probiotic and prebiotic substances that make up a synbiotic are complementary or synergistic. And if the two substances have already been tested separately, must they be tested in combination to give evidence of their health effect? The group’s conclusions, which will undoubtedly steer the direction of future R&D programs, will be published in a forthcoming article in Nature Reviews Gastroenterology & Hepatology.

Probiotics and prebiotics for pediatric populations

Probiotics and prebiotics have been studied for their health benefits in pediatric populations for many years, but in this area scientists appear to have a renewed interest in exploring new solutions. Maria Carmen Collado of Valencia (Spain) covered “Probiotic use at conception and during gestation”, explaining some of the most promising directions for improving infant health through maternal consumption of probiotics.

In recent years, technical advancements have made possible the large-scale production of some human milk oligosaccharides (HMOs); it is now an option to administer them to infants. Evelyn Jantscher-Krenn of Graz (Austria) presented a novel perspective on HMOs, with “HMOs in pregnancy: Roles for maternal and infant health”, giving a broad overview of the many ways in which HMOs might signal health status and how they might be fine-tuned throughout a woman’s pregnancy.

A discussion group on “prebiotic applications in children”, chaired by Dr. Michael Cabana of San Francisco (USA) and Gigi Veereman of Brussels (Belgium), discussed evidence-based uses of prebiotics in children in three areas: (1) prevention of chronic disease; (2) treatment of disease; and (3) growth and development. While the latter category has the best support at present (specifically for bone development, calcium absorption, and stool softening), the other two areas may be ripe for more research and innovation. The chairs are preparing a review that covers the outcomes of this discussion group.

Next year in Banff

ISAPP’s next annual meeting is open to scientists from its member companies and will be held on June 2-4, 2020 in Banff, Canada.

 

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

L. rhamnosus GG for treatment of acute pediatric diarrhea: the totality of current evidence

/in featured, ISAPP Science Blog /by ISAPP

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

For the past several years, studies have been adding to the evidence base on the efficacy of Lactobacillus rhamnosus GG for the treatment of pediatric diarrhea. A new systematic review and meta-analysis led by Prof. Hania Szajewska concluded that Lactobacillus rhamnosus GG is effective for treating acute diarrhea in hospitalized children, even when a 2018 null trial (Schnadower et al. 2018) was included.

“Despite a recent large RCT demonstrating no effect of L rhamnosus GG, current evidence shows that, overall, L rhamnosus GG reduced both the duration of diarrhoea (with a higher impact in European countries) and hospitalisation in inpatients.”

The authors acknowledge that the quality of evidence for this conclusion is low: 13 of 18 included studies suffered from problems with randomization, allocation concealment, blinding, and/or follow‐up. However, the rigorous process used to assess the current state of evidence provides confidence in the paper’s conclusions.

In an editorial in Alimentary Pharmacology & Therapeutics, Prof. Eamonn Quigley suggests that reports dismissing L. rhamnosus GG as ineffective (for example, see The Washington University School of Medicine opinion, “Probiotics no help to young kids with stomach virus“) were premature.

As Prof. Quigley points out, it is necessary to put the findings of the null study into context. He states several reasons why the Schnadower et al. 2018 study may not have shown an effect of L rhamnosus GG, even though previous studies had. Notably, the rotavirus vaccination status of the subjects – with two-thirds of the study population having been vaccinated – seemed important. Subgroup analysis showed that the probiotic was more effective among children who had not been vaccinated for rotavirus.

In addition, as discussed in a previous ISAPP blog, the timing of initiating probiotic therapy is likely an important factor. In the null trial, the average time of diarrhea prior to treatment was 53 hours, and subjects were enrolled up to 72 hours after onset of diarrhea – likely too late to have a possibility of positive impact by the probiotic.

For now the ESPGHAN recommendation to initiate L. rhamnosus GG treatment in conjunction with rehydration therapy early after the onset of diarrhea in children can still be supported by the totality of evidence.

Both Prof. Hania Szajewska and Prof. Eamonn Quigley serve on the ISAPP board of directors.

Effects of the food matrix on probiotic’s efficacy: how much should we care?

/in featured, ISAPP Science Blog /by ISAPP

By Gabriel Vinderola PhD, Researcher at the Dairy Products Institute (National Scientific and Technical Research Council – CONICET) and Associate Professor at the Food Technology and Biotechnology Department, Faculty of Chemical Engineering, National University of Litoral, Santa Fe, Argentina.

The issue of to what extent food components may affect probiotic efficacy when compared to the strain delivered as supplement has lately been the subject of debate. This is especially so in the context of the Codex Alimentarius guidelines on probiotics, presently under development.

When considering the importance of the food formulation delivering the probiotic, it’s worthwhile to keep in mind that people may get their daily probiotic together with an enormous variety of foods. For instance, one person may get the probiotic at breakfast along with a yoghurt or with cereal, whereas another person may choose to consumer a fruit juice, while a third may get the probiotic dose before a meal consisting of pasta, meat and vegetables. In those cases, the same strain can undergo gastrointestinal passage in the context of very different food exposures. Does this suggest that perhaps the specific food format is not so critical? What does research tell us?

An interesting, however in vitro, study was conducted by Grześkowiak et al. (2011). In this work, Lactobacillus rhamnosus GG was recovered from more than 12 foods and supplements and its ability to inhibit food pathogens was assessed in vitro. Authors showed that even when the inhibitory capacity was quantitatively different among isolates, the qualitative probiotic capacity of inhibiting pathogens was present in all of them. That is to say, the probiotic capacity had been retained to a somewhat greater or lesser degree, regardless the matrix.

Few human studies have measured to what extent a health endpoint changes when a probiotic is delivered in different food matrixes. For instance, Saxelin et al. (2010) showed that the administration matrix (capsules, yogurt or cheese) did not influence the faecal quantity of lactobacilli, but affected faecal counts of propionibacteria and bifidobacteria. However no health endpoint was considered in this study. Several studies demonstrate that dairy products are able to confer enhanced protection during gastrointestinal transit in in vitro settings (Vinderola et al., 2000; Sagheddu et al., 2018; da Cruz Rodrigues et al., 2019), suggesting that dairy products may be better at delivering an efficacious dose of probiotic. But again, no clinical endpoint was measured in these studies.

The first comparative study on the probiotic capacity of a strain delivered in food or supplement was reported by Isolauri et al. (1991). Authors demonstrated that Lactobacillus GG either in fermented milk or freeze-dried powder was effective in shortening the course of acute diarrhea. Later on, Meng et al. (2016) found similar patterns of immune stimulation when studying the impact of Bifidobacterium animalis subsp. lactis BB12 administration in yoghurt or capsules on the upper respiratory tract of healthy adults.

As these kinds of studies are scarce, we can look to meta-analysis where the same strain is compared for the same clinical endpoint, but in studies conducted by different groups in different matrixes. For instance, Szajewska et al. (2013) concluded that Lactobacillus GG delivered in capsules or fermented milk significantly reduced the duration of diarrhea and Urbańska et al. (2016) reported that L. reuteri DSM 17938 delivered in either capsules or infant formula reduced the duration of diarrhoea and increased the chance of cure.

In vitro studies find that survival of the probiotic delivered in different food matrices through a (simulated) gastrointestinal transit may quantitatively differ, but no matrix completely eliminates probiotic capacity. Human clinical trials comparing different matrices with a clear health endpoint are scarce, but a general conclusion seems to emerge: regardless of the food matrix, the probiotic effect is achieved.  When the data are assessed through meta-analysis, the top of the “levels of evidence” in the pyramid of evidence-based studies, the probiotic capacity exists for the same strain among different studies, conducted by different research groups, using different food matrices.

In many countries regulators require that the probiotic effect be demonstrated in the same food or supplement that will be offered to consumers. This is a conservative approach in the lack of other evidence, but it may be challenging at the same time for probiotic food development, as any new food, even similar to one already existing, may require new human clinical studies to demonstrate efficacy. This approach may raise economic and ethical concerns too, and be discouraging for the future of probiotics.

Surely additional clinical trials directly comparing effects among different delivery matrices would provide clarity on the importance of this factor to probiotic functionality. Until that time, regulators should enable probiotic food manufacturers to offer a sound scientific rationale that bio-equivalency of different matrices could be expected, and thereby circumvent the requirement need to re-conduct human clinical trials on probiotics delivered in new matrices.

 

References

da Cruz Rodrigues VC, Salvino da Silva LG, Moreira Simabuco, F, Venema K, Costa Antunes AE. Survival, metabolic status and cellular morphology of probiotics in dairy products and dietary supplement after simulated digestion. J Funct. Foods, 2019, 55, 126-134.

Grześkowiak Ł, Isolauri E, Salminen S, Gueimonde M. Manufacturing process influences properties of probiotic bacteria. Br J Nutr. 2011, 105(6):887-94.

Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children.

Meng H, Lee Y, Ba Z, Peng J, Lin J, Boyer AS, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ. Consumption of Bifidobacterium animalis subsp. lactis BB-12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults. Mol Nutr Food Res. 2016, 60(5):1161-71.

Pediatrics. 1991 , 88(1):90-7.

Sagheddu V, Elli M, Biolchi C, Lucido J, Morelli L. Impact of mode of assumption and food matrix on probiotic viability. J Food Microbiol. 2018, 2.

Saxelin M, Lassig A, Karjalainen H, Tynkkynen S, Surakka A, Vapaatalo H, Järvenpää S, Korpela R, Mutanen M, Hatakka K. Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yoghurt, or cheese. Int J Food Microbiol. 2010, 144(2): 293-300.

Szajewska H, Skórka A, Ruszczyński M, Gieruszczak-Białek D. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children-updated analysis of randomised controlled trials. Aliment Pharmacol Ther. 2013 Sep;38(5):467-76.

Urbańska M, Gieruszczak-Białek D, Szajewska H. Systematic review with meta-analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children. Aliment Pharmacol Ther. 2016, 43(10):1025-34.

Vinderola G, Prosello W, Ghiberto D, Reinheimer J. Viability of  probiotic- (Bifidobacterium, Lactobacillus acidophilus and Lactobacillus casei) and non probiotic microflora in Argentinian Fresco Cheese (2000). J Dairy Sci. 2000, 83 (9), 1905-1911.

Another day, another negative headline about probiotics?

/in featured, ISAPP Science Blog /by ISAPP

By Prof. Colin Hill, PhD, APC Microbiome Ireland, University College Cork, Ireland

Scientists have a particular job. We try to discover what is unknown and we want to help to create a better understanding of the underlying forces, both physical and biological, that underpin our amazing universe. It is usually a slow and meticulous process. Gathering data usually takes weeks, or months, or years of work and so there is plenty of time to consider the numerous possible interpretations and the limitations and gaps in our understanding. Everything has to be repeated and subjected to statistical analysis. Finally, we publish our findings and our interpretation of that carefully accumulated data. Even this process takes weeks or months (or years) because of discussions with fellow authors and colleagues, numerous drafts of the manuscript, peer review and editorial comment. We are very aware that whatever we have published will almost certainly be repeated, or built upon, and if we are wrong (in either our data or our interpretation) that it will not withstand the test of time. Thus, we are slow and cautious and often qualify our findings with “this suggests” or “this strongly suggests” and we often finish with the unavoidable conclusion that “more research needs to be done”.

Journalists have a particular job. Journalists have to react quickly, perhaps in minutes or hours, to a breaking story or a commission from their editors, on topics with which they may not be familiar, and write short articles or present short pieces to camera that will appeal to the public and have a clear message. Nuance and complexity must often be left for long-form journalism or that as-yet unwritten novel. Being slow and complete and debating all of the possible interpretations is simply not an option. Finishing up with a cautious, equivocal “on the one hand, but also on the other hand” is also not really an option. Very few journalistic pieces end with “more journalism needs to be done”. It may also be difficult to construct a story along the lines of “some good science was well performed and led to careful and understated conclusions, which should really be repeated before we get too excited”.

It is not surprising then that scientists and journalists can sometimes find themselves at loggerheads. “Do probiotics work?” is a very reasonable question that a journalist can ask a scientist. “Well,” responds the scientist, “that depends on what you mean by ‘work’, and which probiotic you are asking about, and for what condition, and quite often strains are called probiotics but they do not fit the definition, and of course, there was that paper published last year which showed ……”. Cue frustration on both sides. Why can’t the scientist just answer the question? And why can’t the journalist understand that just because a question can be simply stated does not mean that it has a simple answer? Ask a doctor “do pills work?” and you might very well get a similarly convoluted answer, but no one would think it evasive. No wonder the scientist sometimes ends up reading the resultant article in frustration – how did the journalist come to that conclusion, where did all my careful explanations go? Of course, most scientists are imagining his or her scientific colleagues reading the article and wondering at the ‘incomplete’ or ‘trivial’ response. While the journalist may well wonder what planet the scientist lives on if he or she thinks that the editor is going to publish a long essay capturing all of the subtlety of the research.

This almost certainly comes across as me implying that scientists are impeccable purveyors of truth and that journalists are willing to sacrifice truth for simplicity, but I truly am not suggesting that. In almost every instance there is no bad faith involved from either party, it is simply the consequence of the different demands placed on two very different and very valuable roles in society.

So, these things will happen. We will see newspaper articles and online pieces (or editorial comments in journals) that do not contain all the nuance and complexity of the complex paper which it is based. We will see press articles that draw simple and reader-friendly conclusions. “Probiotics quite useless”, “Are probiotics money down the toilet? Or worse?”, etc. So, how should we respond? Do we write erudite articles pointing out the limitations of the commentator, coming across perhaps as arrogant or supercilious? [And yes, of course I use the words erudite and supercilious because it makes me feel better than you.] Do we send angry missives complaining about the article, and perhaps risk drawing further attention to it?

If you are asked by a journalist to comment on a paper, or if your local/national paper or favourite website has published an article that you think is unfair, perhaps the way to respond is to have a few simple questions of your own which can be put to journalists and/or readers. Perhaps we can use a checklist such as the following:

  • Is the article describing an original piece of research and was it published in a reputable, peer-reviewed journal?
  • What evidence is there that the strain or strain mix in question is actually a probiotic? Does it fit the very clear probiotic definition?
  • Was the study a registered human trial? How many subjects were involved? Was it blinded and conducted to a high standard?
  • What evidence was presented of the dose administered and was the strain still viable at the time of administration.
  • Were the end points of the study clear and measurable? Are they biologically or clinically significant to the subjects?
  • Did the authors actually use the words contained in the headline? “Useless”, or “waste of money”, etc?

Once these relatively simple questions are answered, then we can move on to the details and the complexities, but that is not where we should start. Of course, if a study is well performed and reaches a negative conclusion we should absolutely acknowledge that. But we can still point out that one strain or strain mix not working under one set of conditions is only evidence of the fact that one particular strain or strain mix does not work under one particular set of conditions. It does not warrant a blanket condemnation or criticism of all probiotics. Maybe ask the journalist to think about the obvious flaws in the headline ‘Headache pill does not cure cancer, all pills obviously a waste of money!”, and ask why the same standards should not be applied to probiotics?

Scientists and journalists have different roles in society, that is clear, but we can assume a priori that both have clear motives and do not want to mislead readers. Let’s start from there and make it easier for both sides to work together to make the public aware of the very real potential, and very real limitations, of probiotics and prebiotics in preserving health in a society in dire need of practical solutions.

Thank You to ISAPP’s 2019 Industry Advisory Committee Members

/in featured, News /by ISAPP

by Dr. Mary Ellen Sanders

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

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

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

Thank you IAC!

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

/in featured, News /by ISAPP

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

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

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

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

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

/in featured, News /by Mary Ellen Sanders

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

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

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

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

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

See here for the full news article about the award.

Reading, writing, and making an impact

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

Bob Hutkins, University of Nebraska-Lincoln, Department of Food Science and Technology and Leslie Delserone, University of Nebraska-Lincoln, University Libraries

For scientists who study probiotics and prebiotics, these are exciting times.  Every day, there are new discoveries and new opportunities.  There certainly are many challenges – obtaining grants, recruiting and mentoring students and postdocs, editorial duties, and maintaining competitive research programs.

But perhaps the most challenging activity is keeping up with the literature. Back in our respective graduate school days, there were only a handful of journals that required regular reading (and most arrived via regular mail in print).  One of us even remembers waiting for mail delivery to learn about the latest science.

There are now dozens of journals that publish high-quality papers on probiotics, prebiotics, fermented foods, gut health, and other relevant topics.  No longer does one have to wait for the latest scientific report – most of us are bombarded with emailed journal highlights, tables of contents, and latest science alerts.

The figure below illustrates this situation.  In 2001 (when ISAPP was formed), there was about 1 probiotic-oriented paper published per day. Now, with prebiotics included, there are more than ten new papers in the literature every single day!

Indeed, just since 2015, there have been more than 12,000 papers on probiotics and prebiotics listed in PubMed. Add in fermented foods, gut health, and methods papers, and those numbers will easily double or triple.

For researchers, clinicians, and other scientists, there are simply too many papers to read and digest.  Thus, for better or worse, many scientists perform a literature triage of sorts, reading papers mainly from so-called high-impact journals.

As a result, probiotic and prebiotic papers published in the top journals inevitably get the most attention, whether deserved or not.  An unfortunate consequence is that papers in other journals sometimes are over-looked.  Perhaps that’s one reason why, based on searches of several citation indexes, about a fourth of all papers published in our field never get cited at all!

So which papers in our field attracted the most attention or had the greatest impact?  Until recently, the only metrics used to assess impact were the journal’s impact factor and an article’s citation score – how many times a particular paper had been cited by other papers. This is no longer the case, as noted below.  But assuming citation numbers actually reflect impact, we’ve compiled a short list of the most important papers in our field.

To do this, we used two multidisciplinary online indexes, Web of Science Core Collection (WoS) and Scopus. The WoS indexes more than 20,000 journals, while Scopus covers more than 30,000 peer-reviewed journals; we limited the WoS search to its Science Citation Index Expanded.  We separately searched the terms probioti* and prebioti* in the article title, looking for papers and reviews published since 1990, and sorting the results for “times cited” or “cited by” from highest to lowest.

For probiotics, there were more than 10,000 (WoS) and 13,600 (Scopus) articles and reviews. As expected, several of the most cited papers were reviews.  Surprisingly, two were reviews on use of probiotics in aquaculture. Indeed, Verschuere et al. (2000) was the second and third most cited study in WoS and Scopus, respectively.  The 2014 ISAPP consensus paper (Hill et al., 2014) was the 2nd and 3rd most cited paper (Scopus and WoS respectively, with 920 and 1,034 citations as of late March 2019).

And the top probiotic paper in our field since 1990?  That would be a Lancet report that described results of an RCT in which Lactobacillus GG was administered to pregnant women and newborns with atopic eczema as the clinical end-point (Kalliomäki et al., 2001). This paper garnered more than 1,500 citations within the WoS, and 1,953 as tracked by Scopus. Among the authors of this study is current ISAPP president, Seppo Salminen. Incidentally, the 4-year follow-up to that same study (Kalliomaki et al., 2003) was the 4th most cited paper in both indexes!

For prebiotics, there were more 3,000 papers listed.  Leading the list of most cited papers is the seminal Gibson and Roberfroid (1995) paper in the Journal of Nutrition that “introduced the concept”.  Papers by Glenn Gibson and his colleagues dominate the list of most cited prebiotic papers.  But the most cited primary research paper on prebiotics was another clinical study from Finland (Kukkonen et al., 2007).

As noted above, citations are no longer the only way to measure impact.  After all, clinicians, industry scientists, and government regulators and policy makers also read and apply published information.  If a paper leads to a new treatment or technology, could there be a greater impact for the social good?

Consider the science paper with perhaps the greatest overall societal impact in the past 20 years. That would be Brin and Page’s 1998 paper published in what at the time was a relatively obscure journal, Computer Networks and ISDN Systems. The article began, in case you haven’t read it, with these six simple words, “In this paper, we present Google”.

Until recently, paper impacts were difficult to measure. But now we have Altmetrics, Twitter, and other ways to assess impact. Given that it usually takes at least a year before a published paper receives a citation in the WoS and Scopus environments, social media provide a way to gauge impact in real-time.  Indeed, a recent editorial in Nature Cell Biology (2018) suggests that plenty of scientists embrace social media. Evidently, many use it to sort through information as quickly as their fingers can tap.

 

Anonymous. 2018. Social media for scientists. Nature Cell Biology 20(12): 1329. doi: 10.1038/s41556-018-0253-6

Brin, S., and L. Page. 1998. The anatomy of a large-scale hypertextual Web search engine. Computer Networks and ISDN Systems 30(1-7):107-117. doi: 10.1016/S0169-7552(98)00110-X

Gibson, G.R., and M.B. Roberfroid. 1995. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. Journal of Nutrition 125(6):1401-1412. doi: 10.1093/jn/125.6.1401

Hill, C., F. Guarner, G. Reid, G.R. Gibson, D.J. Merenstein, B. Pot, L. Morelli, R.B. Canani, H.J. Flint, S. Salminen, P.C. Calder, and M.E. Sanders. 2014. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology and Hepatology 11(8):506-514. doi: 10.1038/nrgastro.2014.66

Hutkins, R.W. 2019. Microbiology and Technology of Fermented Foods, 2nd ed.; Hoboken, N.J., Ed.; Wiley-Blackwell: Hoboken, NJ, USA

Kalliomäki, M., S. Salminen, H. Arvilommi, P. Kero, P. Koskinen, and E. Isolauri. 2001. Probiotics in primary prevention of atopic disease: A randomised placebo-controlled trial. Lancet 357(9262):1076-1079. doi: 10.1016/S0140-6736(00)04259-8

Kalliomaki, M., S. Salminen, T. Poussa, H. Arvilommi, and E. Isolauri. 2003. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 361(9372): 1869-1871. doi: 10.1016/S0140-6736(03)13490-3

Kukkonen, K., E. Savilahti, T. Haahtela, K. Juntunen-Backman, R. Korpela, T. Poussa, T. Tuure, and M. Kuitunen. 2007. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology 119(1):192-198. doi: 10.1016/j.jaci.2006.09.009

Verschuere, L., G. Rombaut, P. Soorgeloos, and W. Verstraete.  2000. Probiotic bacteria as biological control agents in aquaculture.  Microbiology and Molecular Biology Reviews 64(4):655-671. doi: 10.1128/MMBR.64.4.655-671.200

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

/in featured, News /by Mary Ellen Sanders

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

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

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

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

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

ISAPP releases new video providing clarity on prebiotics and their health benefits

/in featured, News /by Mary Ellen Sanders

Consumers often assume prebiotics are the same as dietary fibers—but in fact, prebiotics have a specific scientific definition and come with unique health benefits.

In this new video produced by ISAPP (see here), you’ll get a quick overview of prebiotics: what they are, different ways you can consume them, and their scientifically demonstrated health benefits.

The video describes food sources of prebiotics, including whole grains, beans, onions, garlic, and artichokes, and how to look for prebiotics in supplement or functional food form. It also distills the science into a practical recommendation: a daily intake of 3-5 grams of prebiotics can help improve digestion, support the body’s natural defenses, improve mineral absorption, and regulate energy balance and glucose metabolism.

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

The Children of Masiphumelele Township

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

Gregor Reid PhD MBA FCAHS FRSC, Professor, Western University and Scientist, Lawson Health Research Institute, London, Canada

Just off the main road from Cape Town, South Africa to Simon’s Town, sits Masiphumelele township where challenges of poverty, malnutrition, HIV and the risk of violence face people every day.

It is also the location for the Desmond Tutu HIV Foundation Youth Centre, a safe haven that provides adolescent-friendly sexual and reproductive health services alongside educational and recreational activities for youth living in Masiphumelele and surrounding areas.

To understand some of the dangers that children face, in 2017, about 270,000 people in South Africa were newly infected with HIV, adding to one of the highest HIV prevalence rates in the world. The Tutu Youth Centre aims at helping educate youth to reduce their risk of becoming another HIV statistic.

I was invited there by University of Cape Town Professor Jo-Ann Passmore, a woman not only recognized for her research but whose passion for helping others is reflected in her warm smile (4th from left in group photo). She asked if I would be interested in holding a workshop to illustrate to the youth how using sachets of probiotic bacteria could empower them. I jumped at the chance. On an afternoon break from the Keystone Symposium, thirty researchers joined me along with Jo-Ann and my wife Debbie, a teacher of children with learning disabilities.

After a tour of the areas where children learn on computers, play games in safety, or have personal discussions about sexual health, everyone filled the room with a stunning backdrop of the Nobel Laureate’s image. Having been privileged to meet the Archbishop when he was hosted by St. Joseph’s Healthcare Foundation in 2008, it was a nerve-tingling experience for me.

Giving a lecture on beneficial microbes is hard enough to peers sitting in the back of the room, but to do so with young South Africans was more somewhat daunting. However, it proved to be a lot of fun especially when we had to identify kids who were good leaders (the boys all pointed to a girl), who liked to make stuff and sell it to others (two boys stood out). By the end, we had picked the ‘staff’ of a new company.

The next step was for four groups to decide on the company’s name, what products they’d make from the probiotic sachets (the options were many including yoghurt, cereals, fruit juices, maize), what marketing tools they would use and who they would target to obtain a respectable income.

Interestingly, several of the conference participants seemed less engaged, as if they had never considered how microbiology research could affect real lives. In front of them were children facing huge challenges on a day-to-day basis. In one group, the kids were quiet until my wife brought out pens and paper, then they went to town designing products, names and labels. A lesson for me on how different people need different stimuli to become engaged. The faculty left early to beat the traffic back to Cape Town, so unfortunately, they did not hear the outcome of the children’s work.

When we re-assembled to present the results, I was impressed with what could be created in such a short time. My favourite was the Amazing Maize, a bottle shaped like a corn cob with the idea it would contain fermented maize. It emphasized the importance of marketing and for products to taste and look good to be purchased.

It has been over ten years since Archbishop Tutu applauded us for the Western Heads East project and thanked us for empowering women and youth and contributing to nutrition in Africa. Since then, thanks to the huge efforts of Western staff and students, and more recently IDRC funding and partnerships especially with Yoba-for-life, Heifer International and Jomo Kenyatta University of Agriculture and Technology, over 260,000 people in east Africa are now consuming probiotic yoghurt every week. The children of the South African townships were maybe too young to join in this new wave of microenterprises, but at least now they have heard about it and the importance of fermented food and beneficial bacteria.

In the background of the workshop several wonderful women committed to start up a new production unit using the Yoba/Fiti sachets developed by Yoba-for-life. I left them some sachets for them to try out the process.

But it was me who left with the biggest lesson on how precious each life is, and how those of us with the knowledge, need to provide the means for others to use their own talents to fulfill the purposes of their lives.

No better way than to start with the children.

Prof. Maria Marco joins the ISAPP board of directors

/in featured, News /by Mary Ellen Sanders

ISAPP happily announces that Prof. Maria Marco Ph.D. from the Department of Food Science and Technology at UC Davis has joined the ISAPP board of directors.

Prof. Marco has broad expertise in probiotics, prebiotics, and fermented foods. She has a special interest in lactic acid bacteria (from plant and animal sources) and the mechanisms of their interaction with their hosts.  She is one of the few researchers globally to tackle the important issue of the role of delivery matrix in probiotic functionality. She has more than 70 publications and book chapters.

Prof. Marco serves as the Chair of the Food Science Graduate Group and has mentored over 50 undergraduates, MS students, and visiting scholars, 11 PhD students, and 13 post-docs. She is active in education and public outreach on fermented foods and is a founder of a start-up company on microbial detection.

Prof. Marco serves as an Editor of mSphere and has served as the Guest Editor – Special issue on Food Biotechnology for Current Opinion in Biotechnology (2018). As guest editor of COB, she mediated publication of outcomes from several ISAPP discussion groups.

See her profile here. For more details on what her lab is up to, see here.

See here for the list of ISAPP’s all-academic board of directors.

ISAPP’s prebiotics & probiotics infographic now available in Russian

/in featured, News /by Mary Ellen Sanders

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

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

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

Humpty Dumpty and the Microbiome

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

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

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

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

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

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

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

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

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

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

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

 

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

Late initiation of probiotic therapy for acute pediatric gastroenteritis may account for null results

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

Francisco Guarner, MD, PhD, University Hospital Vall d’Hebron, Barcelona, Spain; Michael Cabana, MD, MPH, University of California, San Francisco, CA, USA; and Mary Ellen Sanders, PhD, International Scientific Association for Probiotics and Prebiotics, Centennial, CO, USA. 

Schnadower et al (1) and Freedman et al (2) conclude that probiotics given to children who presented to emergency departments with gastroenteritis are not effective; however, these new well-conducted trials used probiotics in children who were symptomatic much longer than when current recommendations suggest initiating therapy.  Both studies recruited children that were symptomatic for up to 72 hours or more at time of randomization. Half the cohort of Freedman (2) had diarrhea for 43 hours at randomization. In the study by Schnadower, (1) children were symptomatic at randomization for a median of 53 hours. It is not surprising that probiotic intervention at this late stage was not successful, since most children were close to spontaneous remission. Acute gastroenteritis in high-income countries is usually benign and after 48 hours typically remits spontaneously. These new studies should not change current recommendations (3,4,5) to use probiotics early after onset of pediatric gastroenteritis in conjunction with oral rehydration, consistent with previous beneficial trials.

 

  1. Schnadower D, Tarr PI, Casper TC, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med. 2018; 379(21):2002-2014.
  2. Freedman SB, Williamson-Urquhart S, Farion KJ, et al. Multicenter trial of a combination probiotic for children with gastroenteritis. N Engl J Med. 2018;379(21):2015-2026.
  3. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD003048.
  4. Szajewska H, Guarino A, Hojsak I, et al. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014;58(4):531-9.
  5. Lo Vecchio A, Dias JA, Berkley JA, et al. Comparison of recommendations in clinical practice guidelines for acute gastroenteritis in children. J Pediatr Gastroenterol Nutr. 2016;63(2):226-35.

 

Importance of understanding probiotic mechanisms of action

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

By Prof. Sarah Lebeer, Universiteit Antwerpen, Belgium

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

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

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

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

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

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

ISAPP recognizes Prof. Michael Cabana’s contributions during his board of directors tenure

/in featured, News /by Mary Ellen Sanders

Prof. Michael Cabana’s service on ISAPP’s board of directors has come to an end in 2018—and the remaining board members wish to affirm his rich legacy of contributions, which furthered ISAPP’s mission of advancing the science of probiotics and prebiotics.

Dr. Cabana, Professor of Pediatrics, Epidemiology and Biostatistics and the Director of the Division of General Pediatrics at the University of California, San Francisco (UCSF), joined the ISAPP board in 2008. He served as secretary for five years and treasurer for one year, and was local host for the 2011 ISAPP annual meeting in Berkeley, USA. He chaired discussion groups at eight different annual meetings:

  • 2009: Designing human clinical trials for probiotics
  • 2010: Prebiotics and probiotics in perinatal nutrition
  • 2012: From clinical trials to clinical guidelines:  Reconciling the evidence
  • 2013: Use of probiotics and/or prebiotics to program fetal and newborn health / first 1000 days of life
  • 2014: Infant colic:  Is there enough clinical evidence to support probiotic interventions?
  • 2015: Technology transfer and academic-industry partnerships
  • 2016: Colic update:  IPDMA and mechanisms
  • 2019: Prebiotic applications in children

 

Dr. Cabana was proactive in developing ISAPP responses to media misrepresentations of research by co-authoring letters to the editor in the New England Journal of Medicine (under review) and JAMA Internal Medicine (in press):

  • Guarner F, Cabana MD, Sanders ME. Late initiation of probiotic therapy for acute pediatric gastroenteritis may account for null results. New England J Med. Submitted.
  • Cabana MD, Salminen S, Sanders, ME. Probiotic safety – reasonable certainty of no harm. JAMA Internal Med. In Press.

As outcomes of ISAPP discussion groups or as part of other ISAPP initiatives, Dr. Cabana coauthored several papers, including:

 

Always a congenial and collaborative colleague, Dr. Cabana will be missed by the ISAPP board as he now turns his focus to other professional activities. Dr. Cabana’s UCSF lab has several ongoing trials related to the microbiome and probiotics in pediatric populations.

Prof. Hania Szajewska joins the ISAPP board of directors

/in featured, News /by Mary Ellen Sanders

ISAPP is pleased to announce that Prof. Hania Szajewska MD from the Department of Paediatrics of The Medical University of Warsaw has joined the ISAPP board of directors.

Prof. Szajewska’s depth and breadth of experience in probiotics, prebiotics, and the effects of early dietary interventions on long term health will greatly facilitate ISAPP’s ability to fulfill its mission to advance the science of probiotics and prebiotics.

In addition to conducting clinical trials on probiotics in pediatric populations, Prof. Szajewska has led numerous efforts to systematically review the totality of evidence on probiotics and prebiotics in order to develop evidence-based recommendations where warranted. She has more than 285 publications and 25 book chapters.

Prof. Szajewska serves as the Editor-in-Chief (Europe) of the Journal of Pediatric Gastroenterology and Nutrition and is involved in European Society for Paediatric Gastroenterology, Hepatology and Nutrition in numerous capacities.

Prof. Szajewska replaces Prof. Michael Cabana MD MPH, who is stepping down from the board to embrace new professional opportunities.

See here for the list of ISAPP’s all-academic board of directors.

kelly_swanson

ISAPP plans consensus panel on synbiotics

/in featured, News /by Mary Ellen Sanders

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

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

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

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

The consensus panel members are:

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

ISAPP’s 2019 Annual Meeting Program Released

/in featured, News /by Mary Ellen Sanders

ISAPP is pleased to announce the release of the official program for its 2019 Annual Meeting, scheduled for May 14-16, 2019, in Antwerp. Unlike the 2018 ISAPP meeting in Singapore, which was an open registration meeting, the 2019 event will comprise only invited academic experts and industry scientists from member companies. For program details, see the meeting website.

The 2019 program offers a strong lineup of probiotic, prebiotic and microbiome presentations. Featured topics include human milk oligosaccharides, learnings from the Flemish Gut Flora project, and leveraging political infrastructure to advance important science and public health messaging. Half-day breakout discussion groups are scheduled for May 15th, covering timely topics relevant to both industry and clinical practice, such as recommended dietary allowance (RDA) for live cultures, and the use of probiotics and prebiotics as adjuncts to drugs. Prof. Glenn Gibson will host the “fishbowl”, a session designed to integrate audience and experts’ perspectives in an interactive format; this year’s topic is: What can scientists and industry do to spring probiotics and prebiotics into mainstream health management?

For companies interested in participating in this meeting, now’s the time to join ISAPP and become part of its active industry advisory committee. Details on industry membership can be found here. ISAPP’s industry members help ISAPP achieve its mission of advancing the science of probiotics and prebiotics—see  here for a summary of our latest accomplishments.

Students and fellows will constitute an important presence at the annual meeting. Members of the ISAPP students and fellows association (SFA) will be keen participants, having organized a poster session as well as two SFA oral presentations. The group will also run a half-day parallel student-focused program.

The local host for ISAPP’s 2019 Annual Meeting, Prof. Sarah Lebeer, University of Antwerp, is excited to welcome her ISAPP colleagues to Antwerp. The history of Antwerp goes back to the 4th century and today the city remains an important European cultural and trade center. ISAPP Annual Meeting participants are invited to join a riverboat trip and dinner to get to know this historic city.

 

 

Do you know the difference between fiber and prebiotics? A new ISAPP infographic explains

/in featured, News /by Mary Ellen Sanders

Many people think prebiotics and fiber are the same thing. But according to leading scientists, they’re not. Fiber and prebiotics are both dietary tools to promote health, but you need to know some key differences between these two types of nutrients in order to make the best decisions for your health.

This new infographic summarizes what fiber and prebiotics have in common, and how they are different (including their distinct effects on the gut microbiome). And most importantly of all: you’ll learn how to get them in your daily diet so you can take advantage of their proven health benefits.

The infographic was written by ISAPP board of directors with input from several outside experts and coordinated by the ISAPP science translation committee.

ISAPP Releases a Mission-Based Summary of 2018 Activities

/in featured, News /by Mary Ellen Sanders

The mission of ISAPP is to advance scientific excellence in probiotics and prebiotics. ISAPP is an independent, science-based voice for the probiotic and prebiotic fields. The newly released short summary details ISAPP’s accomplishments in 2018 based around the core value of Stewardship, Advancing the Science, and Education. See here for the summary, also featuring ISAPP’s recent publications.

Thank you to the ISAPP Board of Directors for their leadership, dedication and scientific expertise, making these accomplishments possible.

Thank you to the Industry Advisory Committee for their ongoing support of ISAPP, providing the resources needed for ISAPP to accomplish its mission to advance the science of probiotics and prebiotics.

Click here to see the 2018 Summary.

See all Annual Reports and Short Summaries here.

YOGURITO –the Argentinian social program with a special yogurt

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

Dra. María Pía Taranto, CERELA-CONICET, Argentina and Prof. Seppo Salminen PhD, University of Turku, Finland

It is widely accepted that technologies play a central role in the processes of social change. The Argentinian experience has documented that yogurt can be a promising tool for promoting social development.  The program is called “Scholar Yogurito, the social probiotic” and the probiotic product is called “Yogurito”. This social program began with the development of a probiotic food, in the form of yogurt. This yogurt contains the probiotic strain Lactobacillus rhamnosus CRL1505, whose functional and technological characteristics are widely documented by CERELA-CONICET researchers. These researchers conducted clinical studies that demonstrated that the consumption of this probiotic product improves natural defenses and prevents respiratory and intestinal infections, the infectious events of greatest relevance in childhood. The “Yogurito Social Program” benefits some 300,000 schoolchildren in the province of Tucumán and some 50,000 in other provinces and municipalities of Argentina. This social transfer project, implemented in 2008 in the province of Tucumán, is a paradigm of interaction between the scientific sector, the manufacturing sector and the state, to improve the quality of life of highly vulnerable populations.

The social and economic implications for such translational research are significant and especially pertinent for people living in poverty, with malnutrition and exposure to environmental toxins and infectious diseases including HIV and malaria. This example of probiotic applications illustrates the power of microbes to positively impact the lives of women, men, and children, right across the food value chain. The researchers are looking for grants that would enable them to compare outcomes of schools given Yogurito to schools with no participation in the program.

 

Additional reading:

Julio Villena, Susana Salva, Martha Núñez, Josefina Corzo, René Tolaba, Julio Faedda, Graciela Font and Susana Alvarez. Probiotics for Everyone! The Novel Immunobiotic Lactobacillus rhamnosus CRL1505 and the Beginning of Social Probiotic Programs in Argentina. International Journal of Biotechnology for Wellness Industries, 2012, 1, 189-198.

Reid G, Kort R, Alvarez S, Bourdet-Sicard R, Benoit V, Cunningham M, Saulnier DM, van Hylckama Vlieg JET, Verstraelen H, Sybesma W. Expanding the reach of probiotics through social enterprises. Benef Microbes. 2018 Sep 18;9(5):707-715. doi: 10.3920/BM2018.0015.

 Senior Researcher Maria Pia Taranto and the Yogurito product

 

Maria Luz  Ovejero, a teacher at Primary School 252 Manuel Arroyo y Pinedo, explains probiotics to 4-6 year old children in Tucuman province in Argentina