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I have IBS – should I have my microbiome tested?

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

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

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

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

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

 

Related Reading:

Microbiome analysis: hype or helpful?

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

Here’s the poop on getting your gut microbiome analyzed

 

ISAPP’s 2019 Annual Meeting Program Released

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.

 

 

probiotics calendar

Probiotics in the Year 2018

Prof. Daniel Merenstein MD, Georgetown University School of Medicine

Messages about probiotics seem to be everywhere. It is difficult for me to keep up with the emails, links, and stories I am sent by friends and colleagues. I am regularly asked my opinion about new studies. Null trials seem to really generate the most interest, with some people looking for limitations of the study and others generally over-extrapolating the null results, seemingly at times to generate the brashest headlines.

Today I want to take a step back and share how I see probiotics in 2018.

I just reviewed a 109-page NIH grant focused on a probiotic intervention for use in a resource poor area. Throughout the grant, the authors never once defined probiotics—presumably because the definition is so commonly known. They did define ‘prebiotics’ but they never felt the need to define probiotics. Imagine that: 2018, and probiotics no longer need to be defined lest the authors seem pedantic. This would not have been the case even five years ago.

Probiotics are backed by real science, they are here to stay, and they are impacting both how we practice medicine and how consumers care for their own health. These are real products with some robust outcomes supported by well-done, independent studies. That is worth emphasizing: there is level 1 evidence for certain products and indications. On the other hand, the use of many probiotics is not evidence-based and expectations about some are not realistic. In the real world, products do not work for every indication or study population. Effect sizes and effectiveness for most indications are often small. One of my true hesitations about fecal microbial transplantation* is how nearly every study has over 90% effectiveness. That gives me cause for concern.

Thus, when there is a null trial the skeptics shouldn’t over extrapolate and the probiotic devotees should not attack the authors. We can look to studies on other treatments as an example: In November of this year NEJM published an article that showed a new antibiotic did not work well for gonorrheal pharyngeal infections. What I didn’t see were any headlines stating, “Antibiotics don’t work for pharyngeal infections.” But headlines involving probiotics often make erroneously broad generalizations. There clearly are indications for which no probiotic has been or will be shown to work. Selling a probiotic for that indication is clearly unethical. But considering the robust evidence base we have for the indication of probiotics for gastroenteritis, it is inappropriate – after 2 null trials – for headlines to read, “Probiotics Do Not Ease Stomach Flu” or “Probiotics No Better Than Placebo for Gastroenteritis”.

This fall I spoke about probiotics at two conferences, the annual meetings of the American Academy of Family Physicians (AAFP) and the annual meeting of the Academy of Nutrition and Dietetics  (FNCE). I had never spoken at either conference. With the help of a colleague, I gave two talks at AAFP; both were over-registered with all 600+ spots taken. At the FNCE, the talk was also over-registered with 350 in attendance. The level of interest in probiotics was astonishing.

What I learned from my talks is that as long as there are well-designed studies demonstrating benefits, professionals are open to probiotics and will use them correctly. Further, both the FNCE and AAFP audiences shared similar concerns: can you trust that probiotic product labels are truthful regarding contents, and are there any safety concerns? Good science and quality oversight need to continue to address these important concerns.

2018 was a great year for the advancement of probiotics in mainstream medicine. However, I think for physicians to fully embrace probiotics, the probiotic industry will better need to police itself and make sure the products they sell are what they say they are. Then they need to communicate this on the product label, using a valid quality seal (such as offered by USP), so physicians and consumers will be confident about what they are using. If the science continues to advance and we communicate about it responsibly, the use of probiotics will be used appropriately and more frequently – as they should be.

 

*For all my colleagues in the gastroenterology world who have fallen in love with fecal transplant for recurrent C. diff,  the totality of evidence as of this writing is:  187 total patients, 5 studies (2 enema, 2 colonoscopy and 1 via-nasoduodenal tube), and punchline, TWO studies were blinded. The one with the lowest rate of success was the only one that was placebo-controlled and blinded. The other blinded study was donor versus patients’ own stools. Stew on that and feel free to correct me.  

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

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

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

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

Where does our food come from – why should we care?

Dr. Karen Scott, The Rowett Institute, University of Aberdeen,  Scotland

The food we eat feeds our microbes, gives us energy and nutrition, and keeps us healthy. The choices we make about our food clearly affects our health, but also has a huge effect on the world around us. We need to make more effort to choose correctly.

Sometimes it seems that everywhere we look, someone has an opinion on what we should be eating. Television is full of programmes telling us how and what to cook – suitable for a range of abilities. In supermarkets we are continually targeted with special offers and promotions, encouraging us to buy things we do not need, that are not on our shopping list. In magazines there are page long adverts, letting us know many reasons why our lives will be enriched if we purchase product Y, and perhaps even how we will be missing out if we do not. Even newspapers print articles telling us which foods are “super” this week, and will endow us with youthful skin, long life, and/or a svelte figure. Next week there will be another article with a new superfood, and one demoting last week’s superfood to the “standard” food, or even demonising it completely.

Yet even with all this focus on what we should be eating, do we really care about where our food comes from? Shouldn’t we really be more concerned with the provenance and sustainability of our food, rather than whether it is “super”?

Quinoa is a grain with a high nutrient content, high protein content (including all nine essential amino acids) and is also a source of some essential micronutrients and vitamins. By popular measures, a “superfood”. Quinoa is primarily grown in South America (Peru, Chile and Bolivia) where it is an important dietary staple. The increased demand and resultant export of quinoa has contributed considerably to the Peruvian economy. On the other hand, the cost increases associated with the increased worldwide demand means that the local Andean population now struggle to afford to include this healthy food in their own diets. Additionally the enlarged land area now used for quinoa production has reduced the amount of land available to grow alternative crops, and this reduced diversity has a negative impact on soil quality and on wildlife. Not so “super”.

Another healthy food-fad with a negative environmental impact is avocado. The current demand for avocados as part of the ‘green smoothie’ revolution has resulted in considerable deforestation in Mexico to make way for avocado plantations. Avocado trees also need a lot of water, which, given that they are frequently grown in climates with problems of drought, is clearly not sustainable.

The other factor is price – we are constantly persuaded that we should be looking for the best deal, getting those “2-for-1 offers”, or buying our food in the specific supermarket “saving you the most on your weekly shop”. The reality is that we spend a smaller % of our income on food today than we ever have – and this is not because we eat less, far from it. But if we think about it, it is not the large supermarket that loses money when it introduces offers. Buy one get one free offers on, for example fruit, usually mean that the farmer is only getting paid for one of every two oranges sold. Is this fair? If you ask a people doing their food shopping if they think that milk should cost more than water – most people would say “yes of course”. Yet at the milk counter in the supermarket they automatically reach for the “special offer”, cheapest product. Sometimes the farmer gets paid less for the milk he sells the supermarket than it costs to produce. Again if you asked people in the shop if they thought this was fair, they would no doubt say no, but they still reach for the “special offer”, cheapest product. This is already driving smaller dairy farmers out of business. Is this what we want? We as consumers, as well as the supermarkets, have to take responsibility.

Similarly with meat products and eggs. Most people, when asked about the best and most humane ways to look after animals on farms, prefer the low density, outside methods often depicted in children’s story books. Yet when we reach the meat counter in the supermarket we are more likely to reach for the cheaper product than the one from the farm which assures humane conditions, but which may cost twice as much. Such farming methods are more expensive to run, so the products have to cost more. We have to make more effort to include our instinctive morality when we are actually making purchases of food.

We have also become accustomed to being able to buy anything, at any time of year. If we want to buy fruit that is out-of-season in our own country, it will be in-season somewhere else and can be flown across the world for display in our local supermarket. When we ask people if they care about global warming – most will agree that it is a big problem, threatening the world. Yet they will buy specific fruits or vegetables that have been flown 1000s of miles, in aeroplanes contributing CO2 emissions, without a thought. Locally produced food, eaten in season, completely avoids this non-essential contribution to global warming.

Feeding our microbes is easy – they just eat our leftovers. But perhaps we also need to think about them. Food produced in intensively farmed conditions contains more pesticide and antibiotic residues than foods produced less intensively. Depending where we live, imported foods may have fewer controls on additives and production methods than those produced locally. Although specific studies have not been carried out to gauge the effect of such residues on our microbes, it is likely that there will be an effect. The healthy compounds in fruits develop best when they are allowed to ripen on the bush/tree and are not harvested unripe and then transported across the world. Our ancestors ate fresh foods in season and produced locally. People living in remote areas of the modern world without access to the diverse range of foods in a supermarket have a more diverse, healthy microbiota than those of us consuming “western diets”. Our microbes do not need, and potentially do not want, intensively produced foods.

Many of us are in the fortunate position of being able to afford to pay a bit more for our food, and thus to support it being produced in the way we would prefer if we stopped to think about it. This is why we DO have to stop to think and not automatically reach for the cheapest product on the shelf.  If we do not support farmers who are producing food in the most humane way, they will go out of business and we will be left with no choice but to buy mass-produced, often imported, food. Is this really what we want?

We have become so accustomed to paying less for our food, and looking for bargains, that we seem to care less about the quality and provenance than the price. Unless we change our outlook we will affect whole populations and environments forever. We need to stop the disconnect between our thoughts about what our foods should be, and what we actually buy, and we need to do it before it is too late.

Minimum criteria for probiotics: ISAPP perspectives

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

During its 2018 annual meeting (June 5-7), ISAPP convened a group of 30 participants from 13 countries to address issues associated with global harmonization of regulations for probiotics and prebiotics. This topic was of interest due to the broad international presence at this meeting, ISAPP’s first in Asia. The goal of this group was to provide regulators guidance derived from this assemblage of experts regarding the minimum criteria a probiotic food or supplement should meet. Drs. Seppo Salminen, Yuan-Kun Lee, and Gabriel Vinderola, who chaired this group, recently completed a summary titled “ISAPP position statement on minimum criteria for harmonizing global regulatory approaches for probiotics in foods and supplements”.

In December of 2017 the International Probiotic Association (IPA) presented a proposal to Codex Alimentarius – a recognized body that develops global standards and guidelines related to foods – regarding establishment of guidelines for probiotic foods. Codex Alimentarius accepted this proposal and requested that Argentina prepare draft guidelines to be considered in the 2018 session of the Codex Alimentarius  Committee on Nutrition and Foods for Special Dietary Use. ISAPP representatives and group coordinators (Sanders, Salminen and Vinderola) took part along with IPA in a scientific meeting in Argentina to present the ISAPP views to local authorities and experts.  IPA hopes that these efforts will lead to harmonized regulations since “this lack of harmonization in industry practice and legislation remains and often leads to serious issues and concerns for the probiotics industry, regulators, and even consumers in regard of quality, safety and labelling.” (Page1 of the proposal)

As the efforts of harmonization of regulations for probiotic foods through Codex progresses, ISAPP offers – through this summary document – its perspectives on minimum criteria for probiotics. The ISAPP group’s conclusions echo the principles outlined in the IPA proposal. Our hope is that this ISAPP document will provide useful perspective to local regulators. As of this writing, Prof. Salminen has delivered this document to the Codex representative at the Finnish Ministry of Agriculture and Food. We hope that further dissemination of the perspectives in this document will contribute to a science-based approach to global harmonization of regulations for probiotics.

See the document for the list of minimum criteria.

Forthcoming changes in Lactobacillus taxonomy

Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

I was privileged to be included in a small meeting of scientists, both academic and industry, who met last week in Verona to discuss changes in Lactobacillus taxonomy. The first objectives of the meeting were to clarify with industry the need for the proposed changes and to clarify the methodology that will be used. The second objectives were to discuss at large potential consequences and approaches to address them.

Changes to the Lactobacillus genus

Experts from the Taxonomic Subcommittee for Lactobacilli, Bifidobacteria and Related Organisms agreed that the genus Lactobacillus is too heterogeneous and dividing this genus into several genera is inevitable. The need for this taxonomic ‘correction’ has been known for a long time, but until recently, the methodologies needed to reliably group the current Lactobacillus species into new genera were not available. But earlier this year, a paper by Salvetti et al (2018) analyzed 269 Lactobacillus and related (e.g., Pediococcus, Leuconostoc, Fructobacillus, Oenococcus) species and showed that the Lactobacillus genus comprises 10 phylogroups (see box). Each of these phylogroups represents at least one new genus. These same 10 phylogroups were observed using three separate approaches [phylogenetic analysis of 16S ribosomal DNA sequences, whole genome sequence analysis, leading to the comparison of 72 shared housekeeping genes (the core genome), and the comparison of average amino acid identity and percentage of conserved proteins], providing strong evidence that these groupings are robust. Commercially important Lactobacillus probiotic strains span at least 7 of those newly defined phylogroups; food fermentation lactobacilli cover even more.

lactobacillus_info

Although these 10 phylogroups were identified by this study, the current genus Lactobacillus could ultimately be resolved into 10 or up to 23 genera, depending on the cut-off values used for the different approaches. If researchers choose to split the genus into fewer new genera, it increases the chance that taxonomic changes will be needed in the nearer future. If they split the genus into more genera, it increases the chance that nomenclature will remain stable.

The names of the new genera are not decided. New names must be published (or validated) in the International Journal of Systematic and Evolutionary Microbiology. The authors of the publication will propose the new genus names. All species will be retained and their species names will not change. To minimize disruption, researchers will try to propose new genera names that begin with the letter “L”. Because “Lactobacillus” is a masculine Latin noun, the new genus names must be masculine for the species names to be retained.

A silver lining

Critics of these changes may suppose that adhering to taxonomic convention is their only purpose. But a classification system that better reflects genetic relatedness of the species may reap other benefits. As evidence for clinical benefits accumulates (summarized in open access review “Probiotics for Human Use”, 2018) and investigations provide insight into probiotic mechanisms of action, a clearer image of mechanisms and functions associated with particular taxonomic groups may emerge. The concept of core, shared benefits that were not strain-specific but linked to higher taxonomic groupings was explored in two ISAPP publications [Hill et al. (2014) and more in depth in Sanders et al. (2018)]. Reconsideration of clinical evidence and its relationship to new genera might prove enlightening.

What can be done to minimize confusion?

The meeting attendees brainstormed potential complications that might result from changing genus names. Company representatives in general considered that internal changes could be managed, although resources would be required to update names on all different paperwork and labels associated with commercial products (for example, marketing materials, product information, certificates of analysis, labeling, import/export certificates). The 2002 WHO/FAO probiotic guidelines, as well as the 2017 CRN/IPA guidelines, indicate that the genus, species and strain designation should be included on product labels. Further, the name used should reflect current nomenclature. This requirement is reflected in some national regulations. Therefore, genus name changes will necessitate label changes.

Further, it was emphasized that a clear document should be prepared and endorsed by reputable organizations (EFSA, NIH, FDA, medical organizations, and others). The document should: (a) indicate the name changes, (b) provide a clear, concise statement of why the changes were needed, and (c) emphasize that only the names, not the strains, would be different. This could be leveraged by companies to communicate with all stakeholders. End-users of probiotic products would likely not be a significant communication challenge. Authorities involved with probiotic safety (FDA with GRAS and EFSA with QPS) likely will manage these changes, as they are science-based. More of a concern was communication with other regulators, both at the level of national agencies responsible for probiotic-specific regulations (including countries with positive lists of species that are acceptable as probiotics) as well as authorities involved in import/export of product. Some potential issue with intellectual property may be envisaged, especially in a transition period during which the new names are not routinely used yet.

The bottom line: Name will change but the strains will stay the same 

The current Lactobacillus genus will be split into at least 10, and perhaps as many as 23, genera. No species names will change, but many species – including commercially important ones – will have a different genus names, hopefully beginning with the letter “L”.  Because of the tremendous heterogeneity of the current Lactobacillus genus, Prof. Paul O’Toole concluded his presentation saying “the status quo is not an option.” Some disruptions can be expected from this massive change, but the probiotic field would benefit from embracing these changes and developing strategies to minimize any difficulties resulting from them.

 

Additional information:

The International Committee on Systematics of Prokaryotes (ICSP) and the International Code of Nomenclature of Bacteria are responsible for the naming of bacteria. The subcommittee of the ICSP responsible for naming lactobacilli is the Taxonomic Subcommittee for Lactobacilli, Bifidobacteria and Related Organisms.

The meeting was convened by the Lactic Acid Bacteria Industrial Platform and chaired by Esben Laulund of Chr Hansens, who also chairs IPA Europe. A full report of meeting conclusions is expected to be published in a scientific journal by the end of 2018. Abstracts and program will to be posted on the LABIP website in due time.

The taxonomic hierarchy for Lactobacillus currently is: Domain: Bacteria; Division/Phylum: Firmicutes; Class: Bacilli; Order Lactobacillales; Family: Lactobacillaceae; Genus: Lactobacillus. The lowest order of taxonomy is the subspecies; the strain designation has no official standing in nomenclature. There are currently over 230 recognized species of Lactobacillus, and approximately 10 new species are added each year.

ISAPP Releases New Infographic – Probiotic Checklist: Making a Smart Selection

Not all products labelled “probiotic” are true probiotics. ISAPP just released a new infographic focused on helping consumers make smart selections when examining probiotic products. The infographic addresses identifying products backed by science, effective dosing, and more.

See and download the full infographic here.

See all ISAPP infographics here.

 

happy_baby

Probiotics and D-lactic acid acidosis in children

Prof. Hania Szajewska PhD, The Medical University of Warsaw, Department of Paediatrics, Poland and Prof. Seppo Salminen PhD, Faculty of Medicine, Functional Foods Forum, University of Turku, Finland

See related post ‘Brain Fogginess’ and D-Lactic Acidosis: Probiotics Are Not the Cause

In their recent study, Rao and colleagues1 incriminated probiotics in the induction of D-lactic acidosis (1). Many who benefit from probiotics could be frightened—on the basis of this report—into stopping them, with potentially negative impacts on their health (2). Some probiotic bacteria, including some specific components of the intestinal microbiota, may produce D-lactic acid. Indeed, if plasma D-lactic acid rises sufficiently, it is clinically relevant, causing D-lactic acidosis. D-lactic acidosis has mainly been observed in subjects with short bowel syndrome. However, some authorities have regulated the use of D-lactic acid producing bacteria in infant and weaning foods, but the reasoning for normal infant population has been debated. Even in adults, the safety of D-lactic acid producing bacteria has been challenged, but apart from short bowel patients no evidence on clinical problems has been reported (3).

For this reason, we conducted a review and examined whether D-lactic acid-producing bacteria, acidified infant formulas and fermented infant formulas were potential causes of paediatric D-lactic acidosis (4).

We identified five randomised controlled trials conducted between 2005-2017 with 544 healthy infants. Additionally, some case reports and experimental studies were considered. No clinically relevant adverse effects of D-lactic acid-producing probiotics or fermented infant formulas in healthy children were identified. The only known cases of paediatric D-lactic acidosis were observed in patients with short bowel syndrome (4). It is of importance that human milk also contains lactic acid bacteria and bifidobacteria, some of which may produce D-lactic acid. Some stress situations, such as exercise, may elevate human milk lactate concentrations.  Thus, breast milk D-lactate content needs to be analysed more carefully to compare with fermented infant formulas.

Taken together, our results suggest that neither the probiotics that were evaluated in the studies we reviewed nor fermented infant formulas cause D-lactic acidosis in healthy children.

 

  1. Rao, S. S. C., Rehman, A., Yu, S. & Andino, N. M. Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.  Transl. Gastroenterol.9, 162 (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006167/
  2. Sanders, M. E., Merenstein, D. & Merrifield, C. A. Probiotics for human use.  Bull.43, 212–225 (2018). https://onlinelibrary.wiley.com/doi/10.1111/nbu.12334
  3. Quigley E.M.M, Pot B., Sanders M.E. ‘Brain fogginess’ and D-lactic acidosis: probiotics are not the cause. Transl. Gastroenterol.9, 187 (2018). https://www.nature.com/articles/s41424-018-0057-9
  4. Łukasik, J., Salminen S., Szajewska H. Rapid review shows that probioticsand fermented infant formulas do not cause D-lactic acidosis in healthy children. Acta Pediatrica 107, 1322-1326 (2018). https://www.ncbi.nlm.nih.gov/pubmed/29603358

FDA/NIH Public Workshop on Science and Regulation of Live Microbiome-based Products: No Headway on Regulatory Issues

September 20, 2018

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

On September 16, 2018, the US Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER) and National Institute of Allergy and Infectious Diseases (NIAID) collaborated on the organization of a public workshop on “Science and Regulation of Live Microbiome-based Products Used to Prevent, Treat, or Cure Diseases in Humans”.  I was present at this meeting along with ISAPP vice-president, Prof. Daniel Merenstein MD, who lectured on the topic of probiotics and antibiotic-associated diarrhea.

Prof. Dan Merenstein speaking at CBER/NIAID conference

While regulatory issues are often discussed at other microbiome conferences, the fact that this meeting was organized by the FDA suggested it was a unique opportunity for some robust discussions and possible progress on regulatory issues involved with researching and translating microbiome-targeted products. The regulatory pathways to drug development seem clear enough, but regulatory issues for development of functional foods or supplements are less clear. Jeff Gordon and colleagues have previously pointed out regulatory hurdles to innovation of microbiota-directed foods for improving health and preventing disease (Greene et al. 2017), and at the 2015 ISAPP meeting, similar problems were discussed (Sanders et al. 2016).

The meeting turned out to be mostly about science. Some excellent lectures were given by top scientists in the field (see agenda below), but discussion about regulatory concerns was a minimal component of the day. Questions seeding the panel discussions focused on research gaps, not regulatory concerns: an unfortunate missed opportunity.

Bob Durkin, deputy director of the Office of Dietary Supplements (CFSAN), left after his session ended, suggesting he did not see his role as an important one in this discussion. One earlier question about regulatory perspectives on prebiotics led him to comment that the terms ‘probiotic’ and ‘prebiotic’ are not defined. From U.S. legal perspective he is correct, as there are no laws or FDA regulations that define these terms. But from a scientific perspective, such a statement is disappointing, as it shows the lack of recognition by U.S. regulators of the widely cited definitions developed by top researchers in these fields and published in 2014 and 2017, respectively.

Two issues not addressed at this meeting will require clarification from the FDA:

The first is how to oversee human research on foods or dietary supplements. CBER’s oversight of this research has meant most studies are required to be conducted under an Investigational New Drug (IND) application. From CBER’s perspective, these studies are drug studies. However, when there is no intent for research to lead to a commercial drug, the IND process is not relevant. Even if endpoints in the study are viewed as drug endpoints by CBER, there should be some mechanism for CFSAN to make a determination if a study fits legal functions of foods, including impacting the structure/function of the human body, reducing the risk of disease, or providing dietary support for management of a disease. When asked about this, Durkin’s reply was that CFSAN has no mechanism to oversee INDs. But the point was that without compromising study quality or study subject safety, it seems that FDA should be able to oversee legitimate food research without forcing it into the drug rubric. CBER acknowledged that research on structure/function endpoints is exempt from an IND according to 2013 guidance. But FDA’s interpretation of what constitutes a drug is so far-reaching that it is difficult to design a meaningful study that does not trigger drug status to them. For example, CBER views substances that are given to manage side effects of a drug, or symptoms of an illness, as a drug. Even if the goal of the research is to evaluate a probiotic’s impact on the structure of an antibiotic-perturbed microbiota, and even if the subjects are healthy, they consider this a drug study. With this logic, a saltine cracker eaten to alleviate nausea after taking a medication is a drug. Chicken soup consumed to help with nasal congestion is a drug. In practice, many Americans would benefit from a safe and effective dietary supplement which they can use to help manage gut disruptions. But in the current regulatory climate, such research cannot be conducted on a food or dietary supplement in the United States. There are clearly avenues of probiotic research that should be conducted under the drug research oversight process. But for other human research on probiotics, the IND process imposes research delays, added cost, and unneeded phase 1 studies, which are not needed to assure subject safety or research quality. Further, funders may choose to conduct research outside the United States to avoid this situation, which might explain the low rate of probiotic clinical trials in the United States (see figure).

The second issue focuses on actions by CBER that have stalled evidence-based use of available probiotic products. This issue was discussed by Prof. Merenstein in his talk. He pointed out that after the tragic incident that led to an infant’s death from a contaminated probiotic product (see here; and for a blog post on the topic, see here), CBER issued a warning (here) that stated that any probiotic use by healthcare providers should entail an IND. This effectively halted availability of probiotics in some hospital systems. For example, at Johns Hopkins Health-system Hospitals, the use of probiotics is now prohibited (see below). Patients are not allowed to bring their own probiotics into the hospital out of concern for the danger this poses to other patients and staff. This means that a child taking probiotics to maintain remission of ulcerative colitis cannot continue in the hospital; an infant with colic won’t be administered a probiotic; or a patient susceptible to Clostridium difficile infection cannot be given a probiotic. Available evidence on specific probiotic preparations indicates benefit can be achieved with probiotic use in all of these cases, and denying probiotics can be expected to cause more harm than benefit.

It might be an unfortunate accident of history that probiotics have been delivered in foods and supplements more than drugs. The concept initially evolved in food in the early 1900’s, with Metchnikoff’s observation that the consumption of live bacilli in fermented milk had value for health. Probiotics have persisted as foods through to the modern day, likely because of their safety. The hundreds of studies conducted globally, including in the U.S. until 10-15 years ago, were not conducted as drug studies, even though most would be perceived today as drug studies by CBER. This has not led to an epidemic of adverse effects among study subjects. True, serious adverse events have been reported, but the overall number needed to harm due to a properly administered probiotic is negligible.

According to its mission, the FDA is “…responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health.” Forcing human research on products such as yogurts containing probiotics to be conducted as drug research, when there is no intent to market a drug and when the substances are widely distributed commercially as GRAS substances, does not advance this mission. Further, CBER actions that discourage evidence-based use of available probiotics keeps effective and safe products out of the hands of those who can benefit.

A robust discussion on these issues was not part of the meeting earlier this week.  Researchers in the United States interested in developing probiotic drugs will find CBER’s approaches quite helpful. Yet researchers interested in the physiological effects of, or clinical use of, probiotic foods and supplements will continue to be caught in the drug mindset of CBER. CFSAN does not seem interested. But without CFSAN, human research on, and evidence-based usage of, probiotic foods and supplements will continue to decline (see figure), to the detriment of Americans.

Human clinical trials on “probiotic”
1992-September 20, 2018

 

 

 

ISAPP-initiated systematic review and meta-analysis shows the association of probiotic consumption with reduced antibiotic prescriptions

At the ISAPP meeting in Turku, Finland in 2016, scientists convened a working group led by Dan Merenstein of Georgetown University (USA) along with Irene Lenoir-Wijnkoop of University of Utrecht (the Netherlands) and Danone Research. In their discussions, the group identified a gap in the literature: a systematic review of randomized, controlled trials to determine how antibiotic prescriptions are associated with probiotic consumption for the prevention of common acute infections. The protocol was registered with PROSPERO (registration number CRD42016052694).

The analysis, authored by ten scientists, was recently published—and results showed that infants and children who received probiotics were at least 29% less likely to be prescribed antibiotics. Find the paper here in the European Journal of Public Health.

ISAPP scientists say probiotics deserve consideration as a public health intervention that may reduce the widespread over-prescription of antibiotics.

See the ISAPP press release here, and the Georgetown University press release here.

See here for media coverage of this paper:

http://www.microbiometimes.com/scientific-analysis-shows-probiotic-use-is-associated-with-fewer-antibiotic-/

https://www.pharmacytimes.com/resource-centers/vitamins-supplements/daily-probiotics-may-reduce-kids-need-for-antibiotics

https://www.news-medical.net/news/20180914/Probiotics-could-reduce-the-need-for-antibiotics.aspx

2018 Annual Meeting Report Now Available

The meeting report for the Annual Meeting June 5-7th 2018 ISAPP in Singapore is now available, featuring overviews of the speakers and discussion group conclusions.

Two days of plenary talks focused on the latest science featuring prebiotic and probiotic use in: pediatrics, oral health, allergy immunotherapy, the gut microbiome throughout life, synbiotics, liver disease, honey bee health, chronic gut disorders, and more. The meeting also featured an interesting talk about the changes coming in the nomenclature of the genus Lactobacillus.

The plenary, open sessions were followed by a Discussion Forum on June 7th for invited experts and Industry Advisory Committee Members. The discussion groups focused on:

  • Harmonizing Global Probiotic and Prebiotic Food/Supplement Regulation
  • Fermented Foods for Health: East Meets West
  • Potential Value of Probiotics and Prebiotics to Treat or Prevent Serious Medical Issues in Developing Countries
  • Prebiotics as Ingredients: How Foods, Fibres and Delivery Methods Influence Functionality

Finally, there were over 70 posters presented at the meeting featuring the latest prebiotic and probiotic research from around the world.

Slides and abstracts for the meeting can be found on the ISAPP website under the “Annual Meetings” tab, available to meeting participants only.

definition

ISAPP conducts webinar on definitions in microbiome space for ILSI-North America Gut Microbiome Committee

Dr. Mary Ellen Sanders presented a webinar July 23, 2018 – covering basic definitions of microbiota-mediated terminology – to the ILSI-North America Gut Microbiome Committee, which you can listen to here. The objective was to update the committee about terms with clear and actionable consensus definitions in the microbiome space. ISAPP is committed to proper use of terms such as ‘probiotics’ and ‘prebiotics’, as evidenced by the consensus panels it has convened (see here and here) on these topics. Definitions of some newly emerging terms such as postbiotic, abiotic, and probioceuticals are less clear.

Some issues covered in this webinar include comparison with historic definitions, minimum criteria for commercial probiotic and prebiotic products, contrasting probiotic food with fermented food, and a brief discussion of imminent taxonomy changes for the genus, Lactobacillus.

The webinar is now available here.

live-dead-probiotics

Dead bacteria – despite potential for benefit – are not probiotics

Re-posted from an original blog article by Dr. Mary Ellen Sanders, ISAPP Executive Science Officer

At the 2018 International Scientific Association of Probiotics and Prebiotics (ISAPP) meeting in Singapore, two renowned speakers reported unpublished research documenting the health benefits of dead bacteria.

Prof. Hill showed that an inactivated Lactobacillus strain reduced anxious behavior, reduced cortisol levels, and impacted the microbiome in a mouse model. Prof. Patrice Cani showed that heat-killed Akkermansia muciniphila were sufficient to ameliorate obesity and diabetes in mice. Both professors made the point that these microbial preparations were not probiotics.

Prof. Colin Hill is the lead author on the oft-cited and -downloaded (over 40,000 times) ISAPP consensus paper reaffirming the definition of probiotics, which emphasizes that probiotics must be alive when administered. This, of course, does not preclude health effects of dead bacteria. One just must remember that dead bacteria are NOT probiotics. Many different types of microbe-derived substances such as metabolites, cell wall fragments, enzymes, and neurochemicals, can have beneficial physiological effects. A 2016 review by de Almada et al. lists a couple dozen published studies of physiologically active dead bacteria.

Preserving the long-accepted definition of probiotics as ‘live microbes’ is important to the many stakeholders involved in the field. Consumers should be able to purchase a product labeled as ‘probiotic’ and know that it contains an effective level of live microbes. Regulators should know that a product without an adequate level of live microbes is fraudulent if called a probiotic. Scientists should be able to use the term and have reviewers and readers understand that they are referring to functions of live microbes. An agreed-upon definition enables us to be precise when discussing an issue. Saying that because dead bacteria have a health effect and they should be called ‘probiotics’ is like saying that because vitamin D has a health benefit, the term ‘vitamin A’ should include vitamin D.

What are implications of the fact that dead microbes may have health effects?

Stewards of the probiotic field can expect increased frustration with popular press writers. I’ll use a recent example to make this point. The June 2018 Cooking Light Magazine /Special Gut Health Issue included an article that lists sourdough bread as a top probiotic-containing fermented food. When the error about misusing the term ‘probiotic’ to describe a food that contained no live probiotic bacteria was pointed out to the editor by Jo Ann Hattner, MPH RD author of Gut Insight, Cooking Light chose to ignore advice from an expert and justify their mistake by using an irrelevant observation that both live and dead cells in probiotic products may generate beneficial biological responses. Apparently, the expertise she derived from a paper that described the “probiotic paradox” trumped the considered opinions of global expert scientists/researchers and the FAO/WHO, who agree that probiotics must be alive when administered. It’s quite a simple concept. It is true that some dead microbes may have some health benefit (although evidence of such an effect is much lower than that available from controlled human trials on actual probiotics), but they are NOT probiotics.

Confusion. Some audiences will be confused by the idea that probiotics that are killed can have health benefits. Inaccurate writers, such as the Cooking Light author above, will perpetuate this error. This is unfortunate, since the probiotic concept is a long-standing one, backed by much mechanistic and clinical evidence. Conflating probiotics with dead bacteria will lead to confusion over important aspects of an effective probiotic product.

Overages.  It is not uncommon for commercial products to be formulated with live microbes at time of manufacture that far exceed the number claimed on the label. This is to assure that the product meets label claim at the end of shelf life, as probiotics often die to some extent during storage. Sometimes this ‘overage’ can reach 10-fold more than the level guaranteed on the product, although more typically it’s 2- to 5-fold. If over the course of shelf life the viable count drops to label claim, then dead microbes may comprise as much as 90% of the microbes present. We don’t know if these dead bacteria – although no longer probiotics – have physiological benefits, as no studies have been conducted on this form of inactivated cells, but it’s an interesting possibility. When we study a probiotic product, perhaps that product needs to be characterized by both the level of live and dead microbes that are present. Means of inactivation, such as heat, pressure, irradiation, or sonication, may impact the physiological activity of the resulting dead cells.

Opportunity.  Keeping probiotics alive in commercial products is a challenge. Research such as Prof. Cani’s targets an expanded range of microbes – many isolated from the human GI tract – that cannot be easily grown and stabilized in commercial products. Further, these microbes lack the history of safe use that food-associated microbes have, and so administration of high numbers of these next-generation probiotics will require proof of safety. If these microbes can be killed and still deliver health benefits, the commercialization process could be simplified.

ISAPP may need to consider convening another consensus panel to address these newly emerging terms, such as postbiotic and paraprobiotic. Then we can all be on the same page when using these terms, which have important scientific, nutritional and clinical impact. Of course, even if ISAPP does this, authors may still choose to ignore it.

East meets West at ISAPP’s first meeting in Asia

By Mary Ellen Sanders, PhD

The International Scientific Association for Probiotics and Prebiotics (ISAPP) recently convened its first meeting held in Asia, with the modern hub of Singapore as a host city. The meeting featured a two-day open registration meeting, attended by nearly 250 scientists, health professionals, and industry representatives, and a third day of smaller discussion groups by invitation. The meeting provided a rare opportunity for non-members to attend. It provided a dynamic forum for sharing different clinical experiences and regulatory nuances amongst the continents, as well as allowing attendees to better appreciate the research being performed in the Asian region.

Here are a few speaker highlights:

 

Mimi Tang MD

Tang presented the results of a double-blind, randomized controlled trial examining the effect of probiotic supplementation combined with oral immunotherapy (OIT) to decrease the risk of peanut allergy in children. Peanut allergy is one of the fastest growing food allergies in children. In the Probiotic and Peanut Oral ImmunoTherapy [PPOIT] study, children randomized to the intervention group had increased rates of sustained responsiveness to peanut several weeks after discontinuation of the treatment. Tang discussed the implications of the study, as well as current, larger clinical trials that are building upon these findings.

 

Dr. Bruno Pot

The Lactobacillus genus is taxonomically abnormally heterogeneous. Currently, the 231 Lactobacillus species range from a genome size of 1.23 – 4.91 megabases, have a GC content of 32-57% and an average nucleotide identity that is typical for a family or worse. Such ranges are far beyond what is acceptable for a bacterial genus. Experts are recommending that the current genus should be split into 12 new genera. Some well-known lactobacilli would be re-named, which may have important repercussions commercially and legally.

 

Profs. Colin Hill and Patrice Cani

Hill described how lactase in yogurt cultures improves lactose digestion; he emphasized how mechanisms that drive probiotic activity are complex. Some scientists are searching for a single molecule that drives probiotic health benefits—but it is unlikely to be found.

Hill noted even inactivated (non-living) microbes may have health effects—for example, a study showed that a dead Lactobacillus strain reduced anxious behavior, reduced cortisol levels, and impacted the microbiome in a mouse model. Work by Prof. Patrice Cani showed that heat-killed Akkermansia muciniphila were sufficient to ameliorate obesity and diabetes in mice. Does this suggest that we will need to start quantifying probiotics based on biomass as well as CFU?

 

Profs. Hani El-Nezami, Gregor Reid and Akihito Endo

These three speakers illustrated the important impact of environmental toxins (extremely potent aflatoxins, pesticides, and heavy metals) on humans and wildlife. They showed how certain probiotic strains can decrease aflatoxin absorption and even degrade them; sequester heavy metals and pesticides to reduce their uptake; and enhance resistance to honey bee colony collapse disorder that threatens the world’s food supply.

 

Prof. Wim Teughels

To date, 11 studies have been published on probiotics with a low ‘number needed to treat’ for prevention of dental caries in infants, toddlers, and adults. One study showed the benefits of administered L. reuteri, following children for nine years after they were treated as infants before any teeth had emerged. Also, data exist for probiotics influencing other oral health endpoints, including periodontal infections, oral candida infections, and halitosis.

 

The discussion groups on day three of the conference addressed a range of topics:

  • Possibilities to harmonize global probiotic and prebiotic regulations—Chaired by Seppo Salminen (Finland), Yuan Kun Lee (Singapore), and Gabriel Vinderola (Argentina)
  • Fermented foods for health: East meets West—Chaired by Bob Hutkins (USA), Paul Cotter (Ireland), and Liu Shao Quan (Singapore)
  • Potential value of probiotics and prebiotics to treat or prevent serious medical issues in developing countries—Chaired by Daniel Merenstein (USA), Reuben Wong (Singapore), and Colin Hill (Ireland)
  • Prebiotics as ingredients: How foods, fibres and delivery methods influence functionality—Chaired by Glenn Gibson (England) and Karen Scott (Scotland)

 

These workshops often produce peer-reviewed publications based on the discussion outcomes, so stay tuned for these developments. (See here for a list of ISAPP publications.)

The full meeting report is being developed and will be posted on the ISAPP website shortly.

The 2019 meeting will return to ISAPP’s normal format, hosted by Dr. Sarah Lebeer in Antwerp, Belgium.

 

2018_Singpaore

ISAPP’s First Meeting in Asia is a Huge Success

June 5-7th 2018 ISAPP held it’s first Asian meeting in Singapore. This open registration meeting was a huge success with over 240 attendees from 34 countries.

Two days of plenary talks focused on the latest science featuring prebiotic and probiotic use in: pediatrics, oral health, allergy immunotherapy, the gut microbiome throughout life, synbiotics, liver disease, honey bee health, chronic gut disorders, and more. The meeting also featured an interesting talk about the changes coming in the nomenclature of the genus Lactobaccilus.

The plenary, open sessions were followed by a Discussion Forum on June 7th for invited experts and Industry Members. The discussion groups focused on:

  • Harmonizing Global Probiotic and Prebiotic Food/Supplement Regulation
  • Fermented Foods for Health: East Meets West
  • Potential Value of Probiotics and Prebiotics to Treat or Prevent Serious Medical Issues in Developing Countries
  • Prebiotics as Ingredients: How Foods, Fibres and Delivery Methods Influence Functionality

Finally, there were over 70 posters presented at the meeting featuring the latest prebiotic and probiotic research from around the world.

Next year, ISAPP will be hosting an invite-only meeting in Antwerp, Belgium – May 14-16, 2019. To attend this meeting, join ISAPP as an Industry Member.

      

karen_scott

ISAPP’s Outgoing President: Karen Scott

Dr. Karen Scott of the Rowett Institute of the University of Aberdeen has served as the ISAPP President for the last three years. During her time as President, ISAPP has seen some incredible growth and accomplishments, and the organization is so grateful for her leadership.

Last year, under Karen’s leadership, ISAPP produced a prebiotic consensus panel paper, which remains one of the highest cited papers in nature reviews gastroenterology and hepatology.

In addition, over the last three years the Science Translation Committee has produced nine infographics, four videos, monthly blog posts, and a monthly newsletter focused on disseminating clinical and consumer information on probiotics and prebiotics.

Karen led three successful ISAPP Annual Meetings – Turku in 2016, Chicago in 2017, and ISAPP’s first meeting in Asia which took place in Singapore in 2018. All of these meetings followed her acting as local host for the 2014 ISAPP meeting in Aberdeen.

ISAPP’s mission to educate resulted in numerous outreach activities over the last three years including continuing education opportunities, webinars, the USP expert panel on probiotics, and regulator engagements. In terms of advancing the science, under Karen’s leadership ISAPP has published 21 peer-reviewed articles on probiotics and prebiotics.

Finally, industry involvement in ISAPP has remained strong and steady during Karen’s term, with 40-45 industry members from around the world. These industry members support ISAPP’s activities and participate in the annual meeting each year to hear about the latest probiotic and prebiotic science available.

Thank you so much Karen for your dedication and hard work to advance scientific excellence in probiotics and prebiotics.

bowling_1

ISAPP is coming to Asia – the hidden reason

By Prof. Glenn Gibson

In just a few days ISAPP will host its first meeting outside of Europe or North America, when we have an open conference in Singapore1,2. There are about 200 registrants and we cannot wait. The meetings are always scientifically informative but fun also. These are main drivers behind our annual jamboree, but this year there is another task…… I am hoping that first timers to ISAPP, and particularly our Asian friends, break with tradition and pronounce the name of the organisation correctly.

I have written one blog in the 56 years of my existence. This first was last year on the various social events we have at the meetings. But this was prior to Chicago in 2017, where we had a bowling alley experience. My PhD student Xueden Wang (Holly) has never let us forget her winning efforts at this:

bowling_1

The above picture and Holly’s endless bragging came to an abrupt end however, when we had our lab Christmas party in December3 – also at a bowling alley this time in Wokingham UK:

Let’s call that revenge of the supervisor shall we? The open top bus parade is now cancelled Holly I am afraid. By the way, if you don’t know what Chicago or Wokingham look like, then both are pictured below. I will leave you to guess which is which:

uk

Anyway, I disgress (justifiably). This is therefore my second blog, and there is a reason for dusting off the quill pen and rehearsing the hieroglyphics once more.

In the last few years ISAPP has published 2 consensus papers, one on probiotics and one on prebiotics4. What we cannot agree on, however, is how to say the name of our esteemed society. Some say ISAPP with the I as “eye”, while others say ISAPP (with the I as in sIt). Admittedly, there is a slight bias in numbers as it is possible to count on the fingers of one finger the number of people who use the latter. It is me. So, that makes about 852 attendees at previous ISAPP meetings incorrect.

Think of the full name of the ISAPP organisation and say it to yourself now…………………

Did anyone say Eye-Nternational? Or did you say International?

At this stage, I should just say that the case for the prosecution is concluded and no further witnesses your honour!

However, let’s look at things a little more closely. If the anarchists, heretics and Eye-Sappers get their way then we may need to change the logo of the organisation to:

eye ISAPP_logo

We see the letter “I” in front of many things these days such as i pad, i mac , i max, i alex cross, i pod, i robot. A quick search of the internet (or as some say eyeNternet) suggests that the “I” can stand for individual, imagination or internet, but usually refers to intelligent. We might have to live with ISAPP standing for intelligent sapps. Here is a picture of 2 saps:

 

Still, 852 people can’t be wrong. I’ll put that another way – 852 people are wrong. So the spotlight turns to Singapore to show us the light, the truth and the way forward.

But……. It gets worse. The terms probiotic and prebiotic are not used on products in Europe now as they are an implied health benefit. Let’s put aside that the very body who devised this “rule” have turned down all but about one health claim. If we go along with this puffed up lunacy5 then we might have to call ISAPP:

International Scientific Association for @%?!&.. and @%?!&..

Maybe we can get away with just using the first letters of these disgustingly offensive, abhorrent and abusive terms. So, ISAPP becomes:

International Scientific Association for P@%?!&.. and P@%?!&..

It still does not seem right, so ISAPP becomes:

International Scientific Association for PAP

Now we are getting somewhere, as PAP means Noun. 1. Nonsense, rubbish. 2. Faeces. Verb. To defaecate. e.g. ‘He was so scared he papped his pants.’.” This embodies exactly what ISAPP is all about and where pro/prebiotics work!!! So, I propose another new logo:

ISAPP_logo 

1I’ll be flying there with British Airways. One highlight is always the safety demo where they say “in the unlikely event that the plane should land on water.” I always feel that “unlikely” is not quite definitive enough. If you were to ask at check in about the chances of the 777 landing on water and the reply was “er… well…on balance it is unlikely”, you would probably not board the old crate.

2Travel tip: Always aim for row 13 and upon reaching it say “oh no, me and my luck, I’m in death row again”, it often leads to vacating of the seat next to you.

3Also attended by a group of leading food science researchers, who face such crucial issues as:

  • What is there in a chicken that makes an eggshell?
  • Why do we not eat turkey eggs?
  • Why is marmalade not just called orange jam?
  • How is some cheese orange when it made from milk?
  • Why are small chocolate bars called “fun size” when they are about half of what they should be?

4By the way, in the olden days (1995) I wanted to call prebiotics parabiotics. Only because MASH was on TV at the time and featured paramedics. So these could be known as biotics that help medics.

5Please note that these opinions are those of the author and do not represent the views of EYESAPP, aside from Gregor.

free_webinar_gut

Free Webinar: Why is everybody talking about gut microbiota?

Coming up on Thursday, June 28th ISAPP Board Member Professor Glenn Gibson will be featured in a free webinar discussing gut microbiota. Hosted by the British Nutrition Foundation, the webinar will examine what we know about gut microbiota and what remains to be explored. Research on gut microbiota has indicated the gut has a role in metabolism, immunity, and more!

The British Nutrition Foundation says “This free webinar aims to increase understanding of the gut-brain axis and the evidence for the role of gut microbiota in metabolic health and immunity. We are absolutely delighted to have world renowned experts speaking in our programme including:

  • Professor Ian Rowland (University of Reading)
  • Professor Ted Dinan (University College Cork)
  • Professor Glenn Gibson (University of Reading) “

 
Find out more information and register for the webinar here.

vinderola in vitro blog

The need to improve in vitro testing of future probiotics

By Prof. Gabriel Vinderola, Instituto de Lactología Industrial (INLAIN, UNL-CONICET), National University of Litoral, Argentina and Prof. Seppo Salminen, Functional Foods Forum, Faculty of Medicine, University of Turku, Finland

In a recent review we compared the in vitro tests for probiotics to the in vivo studies to observe if correlations exist.

Lactobacilli and bifidobacteria have been traditionally accepted as probiotics with the basis of their long history of safe use and reported benefits. However, new species, some of them never previously consumed, are being proposed as probiotic candidates. Some basic tests have been suggested for probiotic candidates, but there is a lack of standardized in vitro protocols for the selection of new strains of probiotics. Additionally, safety assessment of new species may have to cover aspects never hitherto considered.

Vinderola and coworkers reviewed the common in vitro selection tests such as exposure to low pH and bile salts, adherence to intestinal mucus or cell lines and prokaryotic-eukaryotic co-cultures that have been traditionally used to predict the functional properties of probiotics.  At the end, the correlation of in vitro results with in vivo performance remained ambiguous. This poses challenges to research as newly proposed probiotics include often novel species never hitherto administered to humans.

The question of safety has been handled by the European QPS system and the US GRAS notifications but questions on efficacy, particularly concerning health claims, would benefit from predictive in vitro tests. These appear to predict more technological properties than safety and efficacy or health benefits.

New standardized systems need to be developed along with detailed sequencing information to be able to predict novel probiotic properties before they are tested in expensive human intervention studies. If the predictive capacity of in vitro tests fails, many potential probiotics will be left on the way from the laboratory to the application in humans and animals.

The lack of standardized protocols for in vitro and in vivo studies hampers comparison of the potential of new species and strains. There is thus a need to conduct selection of potential probiotics in a more robust manner and to focus on well-defined in vitro and in vivo (animal) studies able to predict health benefits that must still be confirmed in human interventions studies with the smallest possible error margin.

For additional perspective on this issue, see blog by Dr. Mary Ellen Sanders: Probiotic Screening: Are in vitro Tests Informative?

 

 

Reference: Vinderola G, Gueimonde M, Gomez-Gallego C, Delfredico L, Salminen S. Correlation between in vitro and in vivo assays in selection of probiotics from traditional species of bacteria. Trends in Food Sci Tech 2017: 68:83-90.

ISAPP to host live webinar: Microbial metabolism associated with health

Update April 16, 2018:  Recording and slides from the webinar available here.

The International Scientific Association for Probiotics and Prebiotics (ISAPP), in partnership with the International Life Sciences Institute (ILSI) Europe’s Prebiotics and Functional Foods Task Forces, has jointly organized a free webinar, titled Microbial Metabolism Associated with Health. The webinar runs April 12th, 2018 at 15:00 CET, and will highlight recent activities of both ISAPP and ILSI on the beneficial aspects of gut microbial fermentation. The specific focus will be on gut microbiota functions, the effects of the intestinal microbiota on selected nutrients and non-nutrients, and the health benefits of fermented foods. Scientists from both academia and industry may find the webinar of interest. Sign up here.

Webinar participants will learn the status of the science making the links between live microorganisms in the diet and host health. The host gut microbiota is a key factor in determining gut function, nutritional status, biochemical transformations of food and the overall impact on health. This diverse microbial community inhabiting the human gut assists in food metabolism and contributes to the bio-availability of nutrients and non-nutrients; it also has an extensive metabolic repertoire that complements mammalian enzymes in the liver and gut mucosa. Microbial metabolism is an important factor to consider when discussing the management of host health and conditions such as obesity and metabolic syndrome.

The enhanced nutritional and functional properties of fermented foods are being increasingly recognized; not only do microbes transform the substrates and form bioactive or bioavailable end-products, but also, fermented foods contain live microorganisms genetically similar to the strains found in probiotics. The webinar will cover the possible interactions of fermented foods and beverages with the gut microbiota, and potential links to health.

The 90-minute live webinar will be hosted on StreamGo, and will include a question and answer period at the end. There is no cost; however, participants are required to register online beforehand.

Speakers:

  • Effects of the Intestinal Microbiota on Selected Dietary Components
    a) Introduction and Background to the Activity (Dr. Colette Shortt, Johnson & Johnson, UK)
    b) Impact of Intestinal Metabolism and Findings (Prof. Ian Rowland, University of Reading, UK)
  • Health Benefits of Fermented Foods: Microbiota and Beyond (Prof. Robert Hutkins, University of Nebraska, USA)

 

Publications from ISAPP and ILSI-Europe related to the webinar topics:

Talking Science with ISAPP’s Science Translation Committee

By Christopher Cifelli, PhD, VP of Nutrition Research, National Dairy Council.

Communicating with others is an essential part of everyday life. We are constantly sharing information about a variety of topics with friends, family, and even strangers. Most of the time the interaction is easy and natural – and sometimes even fun. But, have you ever talked to a scientist or asked a scientist a question?

Scientists love to talk about their research. And, other scientists want other to know about their research. They enjoy expounding on the minute details of their work and can spend hours on the littlest detail. That is one trait that makes a scientist effective – the attention to detail needed to posit hypotheses and then experimentally test them in controlled, thought-out manners. Scientists can talk to other scientists easily – but, ask some of them to explain their work to the average person and it doesn’t always go so well.

ISAPP is composed of scientists that are world-renowned experts on probiotics, prebiotics, and fermented foods. And, like other scientists, ISAPP wants others to know and understand these complex topics so that they can make informed decisions that may benefit their health. The question was – how does ISAPP do that? The answer: focusing on effectively translating the science. I offered ISAPP my leadership of a new committee to take on this task. ISAPP formed the Science Translation Committee nearly 3 years ago with a goal of taking complex scientific topics and making them easy to understand for consumers and health professionals. The result of this effort has been the development of numerous infographics, blog posts, and informational videos that translate years of research into easily digestible nuggets of information that people can use. The most recent infographic focused on dispelling some common myths about probiotics – because, who doesn’t like some myth busting!

Effective science communication is essential – essential because it can help people understand the complex and enable them to make choices that can benefit their overall health. ISAPP – which is grounded in science – will continue to be the voice of probiotic and prebiotic science and work to help people understand these fun and interesting topics. So, check out our website and our resources and start learning!

blog reid elderly

Do dietary effects on gut microbiota promote health in older individuals? Reid and colleagues gain insights into microbiota composition across the lifespan

January 22, 2018. By Dr. Gregor Reid

ISAPP Board of Directors member Dr. Gregor Reid recently co-authored a cross-sectional study in a cohort of over 1000 very healthy Chinese participants from 3 to over 100 years of age in order to gain insights on ‘healthy’ microbiota composition and whether this changes with age. Using next-generation sequencing (Illumina MiSeq platform) and large-scale compositional data analysis techniques, the study demonstrated that there was very little difference in the fecal microbiota composition of individuals between the around 30 years of age and around 100—as long as the individuals were extremely healthy.

The concept of consuming live microorganisms that offer a benefit to the host (probiotics), or a substrate that is selectively utilized by host microorganisms conferring a health benefit (prebiotics), to promote health in aging populations is becoming more popular. However, it is not currently known what constitutes a ‘healthy’ gut microbiota composition, or what specific prebiotic/probiotic might help establish it.

Discussing the study results in a Reddit Ask Me Anything session, Reid explains, “It is hard to pin down outcomes to one factor such as food, and which components of those foods are critical, but seeing the super-healthy elderly having the same microbiota profile as the super-healthy young adult might make us see if some food practices from 75 years ago have returned.”

Although the study design (cross-sectional) does not allow for a cause and effect relationship to be established, the results may signify that the similarity of gut microbes across ages is a consequence of an active lifestyle and good diet—in contrast with previous hypotheses that aging per se affected gut microbiota composition. Based on these findings, it is reasonable to hypothesize that reestablishing a dysbiotic microbiota composition in older adults, to mirror that of a 30-year-old, may promote health. Moreover, the results offer an established baseline microbiota composition by which other cohorts with chronic or acute disease may be compared.