probiotics Archives - Page 7 of 8 - International Scientific Association for Probiotics and Prebiotics (ISAPP)

2018 Annual Meeting Report Now Available

August 8, 2018/in featured, News /by Mary Ellen Sanders

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.

Probiotics for oral health: start young

July 25, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

By Dr. Mary Ellen Sanders

Prof. Wim Teughels from the Department of Oral Health Sciences, Leuven University, spoke at the 2018 ISAPP meeting on the topic of probiotics and prebiotics for oral health. He embraced the opportunity to speak to this audience in part hoping he could convince researchers to consider incorporating oral health endpoints in their future clinical trials.

He did a spot-on lecture, which precisely summarized available evidence for probiotics and prevention of dental caries, management of periodontal disease and reduction of Streptococcus mutans in the oral cavity. This area of research is gaining traction (see here).

One study he discussed is particularly interesting by Stensson et al. 2014 tracked caries in children at 9 years of age. This single-blinded, placebo-controlled study administered L. reuteri ATCC 55730 to mothers during the last month before their baby’s birth and to the children through age one. The number of children receiving the L. reuteri probiotic without caries was significant higher (82%) than in the placebo group (58%). Although there are studies available that show a larger impact, the interesting aspect of this study is that it tests a very early intervention in life that seems to have an effect up to 9 years later. It is an important paper because it opens up the notion of early interventions in life, during microbial ecology development. The main message here is you don’t need to wait until there are teeth to start working on dental health later in life. In fact, interventions for dental health can start during pregnancy and by this:

The pregnant mother will have less pregnancy gingivitis (Schlagenhauf et al. 2016)
The delivered child will be less susceptible to tooth decay and gingival inflammation (Stensson et al. 2014)

We do not know what would have happened if the probiotics were given during the whole 9 years of life. Dentists who are interested in prevention should be interested in such data.

Several meta-analyses have summarized data for dental caries and management of periodontal disease. These reviews are useful in that they summarize the totality of evidence. But combining data on different strains might not be justified, as different strains may utilize different mechanisms to achieve effects, and therefore should not be considered as the same intervention. See here, here, here and here.

In sum, there appears to be a growing body of evidence that probiotic administration may impact several indicators of oral health: dental caries, gingivitis and periodontitis. More research is needed to understand the impact of probiotic supplementation on the oral microbiota and if clinical benefits are mediated by microbiota changes. It’s also important to understand which strains will deliver the strongest benefits, although L. reuteri has several, positive studies, and the importance of dose and temporal factors with dosing.

Dead bacteria – despite potential for benefit – are not probiotics

July 11, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

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.

Efficacy and Effectiveness Studies

July 7, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

By Michael D. Cabana, MD, MPH

In the world of clinical trials, reproducibility (or consistency) of results across different clinical trials improves clinicians’ confidence in an intervention (Hill, 1965). However, when reviewing the evidence for a probiotic or prebiotic supplement, the results are sometimes conflicting. One study claims an intervention may work. Another study claims that an intervention may not work. So how does the clinician deal with this situation?

To know how much confidence to place in any claim of benefit, clinicians need to consider the totality of the evidence and the quality of the studies. One tool is the systematic review process, which in an unbiased manner searches for all studies for a particular intervention, and when possible, combines results into a meta-analysis. The ‘summary’ of these data point to either an effect or no effect. The best way to combine data is using an individual patient-data meta-analysis (IPDMA). In addition, a clinician should determine whether the clinical trial is an effectiveness study or an efficacy study (Singal 2014).

Efficacy or Effectiveness?

Efficacy studies ask, “does the intervention work in a defined (usually an “ideal”) setting?” In general, the inclusion criteria for study participants will be very selective. Patient adherence tends to be closely monitored. The clinicians conducting the trial may be specially trained in the intervention and its application. The intervention occurs in an ideal setting and the risk of other confounding interventions (e.g., unusual diets, concurrent treatments) will be limited.

On the other hand, effectiveness studies ask, “Does the intervention work in a real-world setting?” The inclusion criteria for study participants tends to be less selective. Patient adherence to the protocol is not necessarily strictly enforced. The clinicians conducting the trial tend to be representative of the typical physicians who would treat this condition. The intervention occurs in a more ‘real-world’ setting where the presence of other confounding factors may be present.

For example, two relatively recent studies both examined the effect of a probiotic intervention, L. reuteri DSM 17938 for the treatment infant colic. A study conducted by a team in Italy (Savino et al. 2010) noted that the intervention reduced colic symptoms; however, the study conducted by a team in Australia (Sung et al. 2014) showed no effect on colic.

Why the different results? In the Italian study, all the infants were breastfed. In addition, the breastfeeding mothers limited their dairy intake. The infants tended to be younger (mean age 4.4 weeks) and tended not to have other treatments for colic or gastrointestinal symptoms. In contrast, the infants in the Australian study were breastfed or formula fed. The infants were older (median age 7.4 weeks) and were more likely to have been exposed to other treatment for gastrointestinal symptoms (such as histamine-2 blocker or proton pump inhibitors). The infants were recruited from many different settings such as the emergency department.

Although both the Italian and the Australian study evaluated the same probiotic intervention for the same condition, the studies offer different information in terms of efficacy and effectiveness. Describing a study as either an “efficacy” study or an “effectiveness” study is not always dichotomous. Rather, these studies exist on a spectrum, from being more like an efficacy study versus more like an effectiveness study. In the example above, the Italian study had stricter criteria and fewer confounding factors. As a result, it would tend to be classified as an efficacy study. The Australian study enrolled infants with colic who were older and had a greater likelihood to be exposed to other interventions. This study would tend to be classified as more of an effectiveness study. The fact that the Australian study was a null study does not mean that the intervention was not effective in the ‘real world’. Rather, for the patients enrolled, the treatment was not effective when used in that particular setting and context. Perhaps you may encounter infants with colic who have feeding history and medical history more like the infants from the Italian study. Understanding the context of the studies helps identify those characteristics that may or may not apply to the infants with colic who you may treat in your clinic.

Which is better: Efficacy or Effectiveness?

When developing a new or experimental intervention, an efficacy study might be important to increase the likelihood of detecting a positive change. However, “real world” factors may make a difference in how a product is used. Perhaps an intervention might be inconvenient (due to multiple doses throughout the day) or unpalatable for the patient. Perhaps the dosing regimen is complicated and the primary care providers don’t apply the correct dosing for patients. In these cases, an effectiveness study might be a better guide to how useful the intervention will be in clinical practice.

As a final note, it can be tempting to simply read the abstract of a clinical trial to assess the results of a study. However, in many instances the crucial details of the study (e.g., how the study participants were selected, who was included or excluded, what type of clinical setting was used) are buried in the methods section of the study. Patient diet, exposure to other treatments and comorbid conditions are all common confounding factors encountered in trials evaluating supplements. When reading through the literature and understanding if a study is applicable to your practice, be sure to understand the full context and purpose of the study. “Was this study useful for determining clinical efficacy or clinical effectiveness?” is an important question for readers of probiotic and prebiotic clinical trials. Keeping this question in mind may help you better resolve what may appear to be inconsistency among clinical trials.

East meets West at ISAPP’s first meeting in Asia

June 27, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

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.

Welcome Seppo Salminen – ISAPP’s New President

June 19, 2018/in featured, News /by Mary Ellen Sanders

An interview with Prof. Seppo Salminen

ISAPP President 2018-2021

1) What are your goals as the next president of ISAPP?

My goal is to work together with the board and the members to advance excellence in the science of probiotics and prebiotics and to share research and conclusions with as wide an audience as possible. It is also my goal to leverage ISAPP’s scientific expertise to work with organizations to promote evidence-based applications of probiotics and prebiotics to advance health and well-being of people.

2) What do you hope to see the organization accomplish during your tenure?

ISAPP is engaged now in North America, Europe and Asia so maybe we can be really be global and reach out to South America and connect with researchers in Africa as we have done with Professor Reid earlier. I would like to work toward common goals with more industrial, scientific and regulatory experts from different parts of the world.

3) What changes do you foresee in the field of probiotics and prebiotics in the next few years?

I foresee rapid development in probiotics and prebiotics. There will be novel microorganisms developed and novel sources of prebiotics and this direction leads to challenges in safety evaluation and efficacy demonstration as well as communication of the results to larger audiences.

4) How did you originally become involved in ISAPP?

I was originally invited to one ISAPP meeting, then to the next one, then to the third one and at the end was invited to be a member of the board, which I considered a special honour!

5) Which ISAPP meeting was your favorite so far?

They all have been excellent, but some I remember (each for different reasons) are the ones in Barcelona, New York, Chicago and Berkeley – and now Singapore. Of course, the one in Turku, Finland as well – when you help organize a meeting like that you certainly remember even on a minute-by-minute basis.

Thank you Prof. Salminen and welcome!

ISAPP’s First Meeting in Asia is a Huge Success

June 8, 2018/in featured, News /by Mary Ellen Sanders

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.

ISAPP’s Outgoing President: Karen Scott

June 7, 2018/in featured, News /by Mary Ellen Sanders

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.

Medscape Webinar on Probiotics – Now Available!

June 4, 2018/in featured, News /by Mary Ellen Sanders

“Navigating the world of probiotics: Helping patients make good choices”

This 30-min CME activity, which took place on April 17th, by Medscape is now available online https://www.medscape.org/viewarticle/897109 The webinar features Prof. Dan Merenstein MD and Mary Ellen Sanders PhD – both ISAPP Board Members.

ISAPP is coming to Asia – the hidden reason

May 19, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

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 Singapore^1,2. 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:

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:

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:

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:

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.

ISAPP Releases 2017 Annual Report

May 3, 2018/in featured, News /by Mary Ellen Sanders

The 2017 Annual Report on ISAPP’s activities to advance scientific excellence in probiotics and prebiotics is now available. The Report covers the 2017 Annual Meeting in Chicago IL, as well as the publications, webinars, meetings and other activities accomplished during the past year. Finally, ISAPP is grateful to the 43 Industry Advisory Committee Members who support ISAPP’s endeavors. See more here.

Continuing Education Opportunity on Probiotics and Prebiotics Now Available for Pharmacists

April 12, 2018/in featured, News /by Mary Ellen Sanders

ISAPP Board member and Professor of Medicine, Dan Merenstein MD, served as faculty for a new continuing education activity on probiotics and prebiotics. “The Expanding Health Benefits of Prebiotics and Probiotics” was developed by Pharmacy Times and is available free of charge here (registration is required to log in to access the materials). This concise, practice-oriented review summarizes evidence for probiotic interventions for clinical conditions and is an excellent summary for all healthcare practitioners.

Medscape Webinar on Probiotics April 17

April 10, 2018/in featured, News /by Mary Ellen Sanders

Prof. Dan Merenstein MD and Mary Ellen Sanders, PhD will present a 30 min webinar titled, “Navigating the World of Probiotics: Helping Patients Make Good Choices” April 17 at 12:30 ET*. Developed by Medscape, the target audience is medical professionals. Dr. Sanders will provide basic information about choosing probiotics and Prof. Merenstein will discuss the strength of evidence for different clinical applications for probiotics. The webinar is free, but you must register with Medscape to sign up. Register here.

*An earlier announcement by Medscape listed the wrong time zone.

Updated Clinical Guide to Probiotics Now Available

April 9, 2018/in featured, News /by Mary Ellen Sanders

Want some guidance on knowing which probiotic products have been tested for which clinical benefits, and understand the level of evidence supporting those benefits? Check out the 2018 versions of Clinical Guide to Probiotic Products Available in USA and Clinical Guide to Probiotic Products Available in Canada. Currently, these are the only 2 geographical regions covered by this initiative, although they are considering expanding to other regions. This guide is updated annually. Some changes for 2018 include addition of new indications ‘Mood and affect’, ‘Liver health’, ‘Weight management’ (Canada) and ‘Seasonal allergies’ and ‘Eczema/Dermatitis-Adult’ (United States). Evidence is reviewed independently by six academic experts and graded as Level I (highest), II or III. A grade of Level I requires evidence from at least one properly designed randomized human trial. This guide is produced by the Alliance for Education on Probiotics, and is an industry funded effort (see industry sponsors for US and Canadian versions).

ISAPP to host live webinar: Microbial metabolism associated with health

March 15, 2018/in featured, News /by Mary Ellen Sanders

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 12^th, 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:

Systemic review of the effects of the intestinal microbiota on selected nutrients and non-nutrients. Colette Shortt et al. 2018.
Gut microbiota functions: metabolism of nutrients and other food components. Ian Roland et al. 2017.
Health benefits of fermented foods: microbiota and beyond. Maria L Marco et al (including Robert Hutkins). 2017.

Academics working with industry

March 12, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

by Dr. Colin Hill, APC Microbiome Ireland & School of Microbiology, University College Cork, Ireland

Many scientists have reservations about working with industry. While characterising it as going over to the dark side might be an overstatement, there is a certain wariness that principles may have to be compromised (in terms of the ambition of the work and the freedom to follow your nose that is the supposed hallmark of ‘pure’ research), dull routine work may have to be performed, and publication in the best journals will be unlikely. There may also be concerns that students or post-docs working on ‘industry’ projects may suffer from these constraints, which will restrict their career development. There can also be a perception that the ‘best’ scientists work on fundamental problems, unfettered by the demands of industrial partners or short-term commercial goals. Some of you reading this opening paragraph may be amused at the simplicity of this stereotyping – “no one really thinks like that” – but I can assure you that some do, including a younger version of myself.

I have only really worked closely with industry in the last decade. Before that, I wrote grants which assured potential funding agencies that what I wanted to investigate was incredibly relevant and important, would represent good value for the taxpayers’ investment, but was just a ‘little bit too early’ for industry to take on. I genuinely believed this for the most part, although part of getting older is learning that fooling myself has always been a much easier task than fooling anyone else. Nonetheless, I managed to forge a career in science. I had a reasonable success rate of about one in four or five applications, which still seemed a poor return for the effort involved. I would take my hard-earned funding and do my best to deliver on the promises I had made. On occasion, the grants were successful, and we ended up filing a patent or developing a prototype or a process and essentially delivering on the promises made in the grant application. But all too often I discovered that what we had achieved, or the problem we had solved, was not really the burning issue I had thought it to be, or at least could not be translated for the benefit of society without suitable industry partners. In essence, we had self-tasked ourselves to solve a problem that no one really needed to be solved (or, at least not yet, or not in the precise manner we had solved it).

Of course, on occasion I was successful in getting truly ‘fundamental’ or ‘basic’ grants which were simply aimed at generating knowledge, and these were absolutely vital in developing new skills and opening up new research areas and possibilities. However, over the past decade or more, I have begun to work closely with industry partners. At first, this was driven by changes in funding policy in Ireland which linked scientific excellence to industry relevance – grants had to pass rigorous peer-reviewed scientific assessment, but also had to be validated by an industry partner willing to put skin in the game in the form of co-funding. This necessitated finding industry partners and identifying a research problem together, before developing a solution. I hope that now I have a perspective on both aspects of scientific research – often simplistically referred to as basic versus applied research – and I have good news. Working with industry can be just as scientifically rewarding as not working with industry.

As I have experienced it, working with industry has several obvious advantages.

Relevance. You know the research problem posed is one that genuinely needs solving, and the industrial partner for any solution you may develop is already engaged.
Funding. Once you begin to work with an industry partner, the prospect of getting funding is much higher than in most competitive grant applications and the amount available may be defined by the extent of the problem, not the limit of a particular funding call.
Intellectual capital. Most of the industry people you will be dealing with are also scientists, and they are just as clever, or far cleverer, than you (or me). They will have defined goals but also have the same scientific curiosity which can be harnessed within the project.
Flexibility. If you have embarked on the project and you find you have gone down a blind alley, it is usually possible to have a discussion with your partners and change the project design. You don’t have to go back to the funders for permission to adjust the dreaded Gantt chart and ‘deliverables’, or have to justify to grant reviewers why you have gone off track. If a project extension is required you can often simply argue for it, no need to write a new grant and experience the inevitable downtime ‘between funding’.
Urgency. Working with a student or a post-doc on a problem can be exciting, but sometimes a good or a bad result seems important only to the two of you. It really adds urgency when an industry meeting is looming on the horizon, when you know the funders are directly invested in the outcomes of the experiments, and when the pressure really builds on the team. In these moments some intense brainstorming and problem-solving can be required, which can create a real sense of excitement within the project and which can be a tremendous learning experience for junior members of the team.
Career development. Most of the students and postdocs in the lab will not end up in academia, nor should they. It is valuable training for young scientists to have a first-hand exposure to industry-based science so that they can make an informed choice on their next step in their career.

Are there negatives? Well, honestly, not all industry sponsored research involves cutting edge science. But if you are completely uninterested in the outcomes then don’t take it on. What about bias? Does industry funding create a bias towards positive outcomes? I genuinely have not found this to be the case. Reputable industry partners have no interest in biased results, since the company’s reputation is at stake and of course, no one is more invested in the scientific validity of their product than the industry partner. And given that science is ultimately self-correcting no reputable scientist wants to be associated with misleading outcomes. Individuals on either side can make mistakes or display bias, but that is no less true in the basic sciences.

The ideal academic-industry relationship recognises that there have to be rewards for both partners. For both it is really important that the experiments be conducted to the highest possible standards with appropriate controls. For the academic the right to publish the results in a timely fashion is particularly important when junior scientists are involved and a clear understanding of how results will be disseminated must be reached before the collaboration gets underway. For the industry partner, it is important that the work stay focused on the agreed goals of the project and not veer off into the ‘nice to know’ rather than ‘need to know’ areas of the research problem. As in most things, problems can be avoided by having a clear agreement on the goals, methods and publication strategy and having transparent reporting structures. Further, both sides must put effort into maintaining a good working relationship.

Finally, it is not a binary choice – working with industry obviously does not close off any other type of research you may want to perform. You can still write grants and get funding from other sources. In fact, I would propose that the ideal research mix requires an element of exploratory science to keep the laboratory fresh and industry-funded science to ensure relevance. And when in doubt always defer to the great Louis Pasteur, who said “There are no such things as applied sciences, only applications of science”.

Two Free Webinars on Probiotics!

March 12, 2018/in featured, News /by Mary Ellen Sanders

Both webinars – eligible for continuing education credit – on probiotics involving ISAPP board members are scheduled. The first is scheduled for Thursday, March 15th 11am-noon CST. It features Mary Ellen Sanders, PhD on the topic of “Be a Pre and Probiotic Pro” and is sponsored by General Mills Bell Institute of Health and Nutrition. Register here.

The second, “Navigating the World of Probiotics: Helping Patients Make Good Choices,” is under development by Medscape. Both Prof. Dan Merenstein MD and Mary Ellen Sanders, PhD will speak during this 30 min webinar. It will take place April 17. Register here.

ISAPP Goes to India

February 28, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

By Mary Ellen Sanders PhD and Dan Merenstein MD

ISAPP sent two key-note speakers to the Probiotics Association of India meeting, held Feb 16-17 in New Delhi. Prof. Dan Merenstein MD spoke on “Evidence for clinical indications: how do probiotics measure up?” and Dr. Mary Ellen Sanders addressed “Is it time for live cultures to be included in official dietary recommendations?” Dr. Merenstein also gave a second talk on an ISAPP-supported project: the evidence that probiotic consumption can reduce antibiotic utilization. This is the 3^rd PAi meeting that ISAPP has supported through speaker sponsorship.

The meeting featured talks on synbiotics to prevent late-term sepsis (Pinaki Panigrahi), the impact of diet on the Indian gut microbiome (Yogesh Shouche), autism (Sheffali Gulati) and 10 selected student/young investigator presentations on diverse microbiota/probiotic studies. Because of the high quality student presentations, judges were unable to choose the best to award prizes. The solution: all 10 presentations were awarded 5000 INR, supported by Prof. Pinaki Panigrahi’s Center for Global Health and Development. A poster session and original probiotic-themed drawings (see below for one submission) were also presented.

Dr. Sanders also spoke on “The contribution of probiotics to health” in an event held February 15 sponsored by the Gut Microbiota and Probiotic Science Foundation (India). This event was attended by ~150 professionals in nutrition, medicine and microbiota/probiotic research.

Of course, the trip was not all work. Below, Mary Ellen takes a selfie with her new elephant friend, Sampa.

Probiotics and Good Gut Health. An artistic interpretation by a student, Simranjeet Singh.

Mary Ellen Sanders takes selfie with Sampa, a 62-year old Asian elephant.

Probiotics: the importance of the complete product

February 11, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

February 11, 2018. By Dr. Olaf F.A. Larsen, Assistant Professor (0.2 FTE) at Athena Institute, VU University Amsterdam, The Netherlands, and Science Manager at Yakult Netherlands.

Probiotics are, according to the WHO and later updated by a consensus panel convened by ISAPP, defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. Most scientific literature ties probiotic properties to individual strains, although evidence suggests that some health benefits may generalize to the species or genus level. Another important factor in how a probiotic performs is the type of matrix (e.g., a milk drink) that carries the probiotic. Indeed, many successful commercial probiotic products are largely defined by both the probiotic contained and the final product format. A plethora of probiotic products are available, ranging from fermented milks/yogurts, cereal products, juices and freeze-dried products (powders and pills). Some products claim to be probiotic but lack substantiation, such as “probiotic” pizzas and mattresses. It is likely that the probiotic properties are not solely determined by the probiotic strain itself, but also by the harbouring matrix. Hence, in order to fully understand the parameters that drive functionality of a specific probiotic, the total product should be evaluated.

Recently, the influence of the matrix on measures of probiotic functionality was reviewed. The data suggest that the matrix impacts several parameters, including number of viable probiotic microorganisms present in the product through shelf life and survival of the probiotic through the gastrointestinal tract. As an example, the number of viable microorganisms in the product as a function storage time can be profoundly different depending on the combination of probiotic strains and matrices used. Some products in which lyophilized probiotics are incorporated into a peanut butter matrix can have storage times up to 50 weeks. Whey proteins present in milk may improve gastrointestinal tract survival. Therefore, one should be aware that it is likely that viability of the probiotic will be impacted by the carrier matrix.

Another way that matrix can be important is through delivery of additional beneficial substances. For example, milk products contain various vitamins, calcium and high quality protein. In the case of a fermented probiotic product, the fermentation process may yield functional substances such as antihypertensive peptides. These effects can be considered as “additional benefits” of the matrix, beyond the impact of matrix on probiotic survival both in the product and in your body.

The body of scientific evidence falls short, however, of proving the importance of matrix on health endpoints. For a given amount of probiotics delivered, we lack comparative studies that prove that the end-benefit of one carrier matrix is better than another. Many supportive studies suggest that this will be the case, but until head-to-head human studies are conducted, we don’t know for sure.

Given the impact the matrix exerts on probiotic survival, and the possible effect on probiotic effectiveness, keep in mind the importance of efficacy studies conducted on the complete probiotic product. We need more research to fully understand the role of matrix on probiotic effectiveness, but the strongest evidence comes from studies conducted on the complete probiotic product.

Figure: Determinants of probiotic product parameters (adapted from Flach et al. 2017). Mark B. van der Waal is gratefully acknowledged for producing the artwork.

For another perspective see Does the delivery format affect probiotic efficacy?, March 28, 2018 by Mary Ellen Sanders.

ISAPP BOARD MEMBERS TO PARTICIPATE IN PEDIATRIC PROBIOTIC CONFERENCE IN ITALY

February 7, 2018/in featured, News /by Mary Ellen Sanders

ISAPP Board Members, Professors Michael Cabana MD MPH and Seppo Salminen PhD, will be participating in the 4th Annual Prebiotics and Probiotics in Pediatrics conference in Bari, Italy April 12-14, 2018. Prof. Cabana will be chairing a panel on colic and will discuss findings from a meta-analysis of L. reuteri as an intervention for colic. This meta-analysis, published December 2017, was the outcome of discussion groups convened at the 2014 and 2016 ISAPP meetings, both led by Prof. Cabana of University of California, San Francisco.

Prof. Salminen will share his decades of knowledge of probiotics, colonizing microbiota and pediatric applications in his presentation titled “Bacteriome and Friends.”

Don’t miss the 4th Annual Prebiotics and Probiotics in Pediatrics conference, which is a unique opportunity to meet major experts in the field while learning the most updated basic and clinical research on prebiotics and probiotics for the developing human. The three-day meeting will cover the major novelties in pediatric gastroenterology, obesity, allergy, nephrology, neonatology and the new scenario on gut-brain communication.

Talking Science with ISAPP’s Science Translation Committee

January 31, 2018/in Consumer Blog, featured, ISAPP Science Blog /by Mary Ellen Sanders

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!

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

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.

ISAPP RELEASES NEW INFOGRAPHIC: “PROBIOTICS: DISPELLING MYTHS”

January 22, 2018/in featured, News /by Mary Ellen Sanders

How often do you hear information about probiotics that is just plain wrong? Too often write-ups on probiotics in blogs, websites, articles written by the lay press, and even sometimes in scientific journals is not true to the science. The latest ISAPP infographic corrects several common misconceptions about probiotic dose, sweetened probiotic yogurts, fermented foods, and more. In doing so, this infographic furthers ISAPP’s core values of stewardship, advancing the science and education.

This resource was developed by ISAPP’s Science Translation Committee and approved by the ISAPP board of directors.

Resilience as a measure of health: implications for health claims for foods

January 16, 2018/in featured, ISAPP Science Blog /by Mary Ellen Sanders

January 16, 2018. By Mary Ellen Sanders PhD, Sylvie Binda PhD, Seppo Salminen PhD, Karen Scott PhD

Demonstrating health benefits for healthy people is a challenge faced by those attempting to communicate claims on a health promoting food. Foods, in many global regulatory frameworks, are intended for the general population. Therefore, any benefits ascribed to them, the logic goes, must be demonstrated in the generally healthy population.

An old concept has new-found notoriety in the context of offering an approach for establishing health benefits for healthy people. It is the concept of resilience. In an ecological sense, resilience refers to the ability of an ecosystem to withstand perturbation and continue normal function, i.e. maintain homeostasis. In the context of human physiology, resilience enables a host to remain healthy even when exposed to a stress, or to recover from a stress faster. A variety of external challenges such as drugs, pathogens, emotional stress, poor diet among others, may perturb normal physiological function or disrupt the gut ecosystem. Individuals more able to maintain stability of physiological functions when exposed to such challenges would be healthier than those who cannot maintain stability. Thus, a food would be considered to have a beneficial effect if it could increase the resilience of the consumer to a challenge.

This concept was described in an EFSA guidance document on biological relevance of data in scientific assessments:

“When subject to a disturbance, a biological system enters in a transient state: a process variable has been changed and the system has not yet reached steady state. Some systems, including humans, have the capacity to regulate their internal environment and to maintain a stable, relatively constant condition of properties; it is called ‘homeostatic capacity’. Resilience represents the amount of disturbance that can be absorbed by a system before the system changes or loses its normal function, or the time taken to return to a stable state, within the normal operation range following the disturbance…” [Reducing] “homeostatic capacity … might be detrimental, whereas increasing the capacity could be beneficial.”

This concept aligns with the definition of ‘health’, which includes the ability to adapt to the environment.

Resilience of gut microbiota

This concept of resilience can be applied to the human microbiota as an ecosystem. Once established in early childhood, our colonizing microbiota reaches a relatively stable state. Although brief fluctuations occur, especially in relation to daily diet and medicines used, the microbial ecosystem of a healthy adult provides relatively stable functionality. Disruption of the microbiota by repeated stressors can be associated with poorer health. There seems to be a solid rationale that the ability of the colonizing microbiota to resist, or recover quickly from, perturbations reflects a person’s ability to remain healthy. The microbiota stability may be indicated in either populations of bacteria or their metabolic output.

Homeostasis and health: a statistical approach

“A statistical approach to measuring improved health was proposed by Dr. Dan Tancredi at the 2010 ISAPP meeting. It is reprinted here from: Sanders, et al. 2011. Health claims substantiation for probiotic and prebiotic products. Gut Microbes 2:3, 1-7.

An approach to measuring improved health may be to measure homeostasis, as suggested by D. Tancredi. From a statistical point of view, if an intervention were able to minimize the variation around the mean for a specific measure (even in the absence of changing the mean; Fig. 1), it could be a reflection of improved health, assuming a biological rationale exists that tighter control of the parameter is physiologically advantageous. In other words, lessening the fluctuation around an individual’s biomarker could be interpreted as contributing to improving health. This novel idea emphasizes the importance of homeostasis as a focus of studies on health, and provides a rationale based in solid statistical theory as a way to measure this.

One challenge to demonstrating the value of this approach is to identify appropriate biomarkers that could be studied. The following properties would be important to a relevant biomarker for homeostasis:

maintaining moderate levels of the biomarker is associated with good health;
high or low values are associated with ill health;
biomarker levels in the same person can fluctuate over time; and
reducing the magnitude or duration of such fluctuations in healthy people is considered desirable (Fig. 2).

Such a biomarker could be an individual endpoint or be formed as a ratio of two other biomarkers, when maintaining the same relative amounts of the two component biomarkers would be desirable.

Assuming a biomarker with the above properties is available, it could be used as the outcome measure in a randomized controlled trial to provide evidence that the experimental food is able to improve the maintenance of health in humans. Statistically, the trial would be set up to address the hypothesis that the experimental substance is associated with lower variation in biomarker levels, compared to the control arm, in subjects who were healthy at baseline. Such a trial would be able to use information on within-person variations in biomarker levels, even those who did not become ill. Partly as a result of the more efficient use of study data, such a trial would require far fewer subjects than an intervention that instead addressed the hypothesis that treatment is associated with fewer healthy persons becoming ill.

A mounting understanding of the value of stability of the colonizing microbial communities makes this endpoint an attractive one to consider. Perturbation of gut microbiota is associated with intestinal dysfunction, as illustrated during antibiotic treatment. Specific probiotics have been shown to promote a quicker rebound from antibiotic-induced microbiota disruption, including a study on Lactobacillus rhamnosus GG (LGG) (Cox et al. 2000). This paper concludes ‘…that a key mechanism for the protective effect of LGG supplementation on the subsequent development of allergic disease is through the promotion of a stable, even and functionally redundant infant gastrointestinal community.’

However, it would be useful to define additional biomarkers that would be appropriate targets for this type of investigation.

In pediatric nutrition, the measurement of metabolic homeostasis has become a standard approach when developing infant formulas (Heird, 2005). The concept of homeostasis as a model to distinguish between foods (including food supplements) and medicinal products was explored by the Council of Europe (2011), and is an interesting correlate to the above hypothesis.”

Conclusions

The recent recognition by EFSA that maintenance of homeostasis is a valid measure of health provides an opportunity to apply this concept to validate health benefits of specific foods and food ingredients. Stability of microbial populations, microbial metabolism or host physiological readouts could be measured to reflect the concept of resilience. Since there is no definitive composition of a ‘healthy human microbiota’, a more reasonable target for measuring positive impacts of a probiotic on the microbiota would be reflected not in absolute levels of specific microbes but in the ability of a specific probiotic or prebiotic to bolster the resilience of the microbiota.

References:

Council of Europe. Homeostasis, a model to distinguish between foods (including nutritional supplements) and medicinal products 2008; (Accessed February 24, 2011, at http://www.coe.int/t/e/social_cohesion/soc-sp/homeostasis%20%282%29.pdf ).

Cox MJ, Huang YJ, Fujimura KE, Liu JT, McKean M, Boushey HA, et al. Lactobacillus casei abundance is associated with profound shifts in theGunderson LH, 2000. Ecological resilience: in theory and application. Annual Review of Ecology and Systematics, 31, 425–439.

EFSA guidance document: Guidance on the assessment of the biological relevance of data in scientific assessments; July 12, 2017; EFSA Journal 2017;15(8):4970

Heird WC. Biochemical homeostasis and body growth are reliable end points in clinical nutrition trials. Proceedings of the Nutrition Society 2005; 64:297-303.

Huber M, Knottnerus JA, Green L, van der Horst H, Jadad AR, Kromhout D, Leonard B, Lorig K, Loureiro MI, van der Meer JW, Schnabel P, Smith R, van Weel C, Smid H (2011). “How should we define health?” BMJ. 343:d4163.

Sanders, et al. 2011. Health claims substantiation for probiotic and prebiotic products. Gut Microbes 2:3, 1-7; May/June 2011

ISAPP works to have evidence-based usage of probiotics to prevent antibiotic-associated diarrheoa implemented in UK

January 12, 2018/in featured, News /by Mary Ellen Sanders

January 12, 2018. Antibiotics are amongst the most commonly prescribed drugs in UK hospitals. However, as well as treating infection they can cause disruption to the gastrointestinal microbiota. This can lead to the relatively common side-effect of antibiotic-associated diarrhoea (AAD) which often delays discharge. More concerning is that a disruption to the normal gut microbiota can lead to reduced resistance to opportunistic pathogens such as Clostridium difficile, leading to C. difficile infection, a potentially severe or fatal infection. Based on the available evidence, probiotics are a safe and effective adjunct to antibiotics to reduce the risk of developing AAD and for the primary prevention of CDAD. The International Scientific Association of Prebiotics and Probiotics has reviewed available data and supports several published assessments, which recommend probiotics as adjunctive therapy for prevention of AAD and CDAD.

This effort was led by Dr. Claire Merrifield BSc MBBS PhD, Speciality Registrar in General Practice, St. Mary’s Hospital, Imperial College Healthcare Trust, Imperial College London and Prof. Daniel Merenstein, MD, Department of Family Medicine, Georgetown University Medical Center and ISAPP Board Member and Treasurer.

Read full recommendation here, which will be sent to NICE and Public Health England.

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