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Defining emerging ‘biotics’

By Mary Ellen Sanders PhD

From its inception, ISAPP has been committed to clarity in both the definitions and the contextual use of terms in the fields of probiotics and prebiotics fields. This is reflected in the FAO/WHO probiotic guidelines working group conducted immediately prior to the first ISAPP meeting in 2002, as well as our more recent consensus panels convened on probiotics (2013), and prebiotics (2016). We also have additional panels in progress on synbiotics (convened in May 2019 in Antwerp), fermented foods (scheduled for September) and postbiotics (scheduled for December).

A recently published paper, Emerging Health Concepts in the Probiotics Field: Streamlining the Definitions, addresses definitions of many newer terms in the ‘biotics’ arena, including probiotics, prebiotics, synbiotic, pharmabiotics, postbiotics, probioceuticals, paraprobiotics, oncobiotics, psychobiotics, and live biotherapeutic products. In my opinion, although this paper provides useful discussion of issues surrounding the proliferation of terms in the ‘biotics’ area, it falls short of providing clear direction for the field and indeed may well add to confusion by introducing unnecessary, new and poorly defined terms.

For example, the term ‘symbiotics’ is perpetuated, presumably as a synonym to synbiotic. It was a missed opportunity to clarify that the term ‘synbiotic’ is derived from the Greek root ‘syn’ meaning ‘with’ or ‘together.’ The term ‘symbiotic’ is simply incorrect, adds nothing and should be eliminated altogether.

This paper fails to advance the ISAPP consensus definition of prebiotic, published in 2017, by lead author Glenn Gibson, co-inventor of the terms ‘prebiotic’ and ‘synbiotic’. It is not clear whether the authors disagree with the ISAPP consensus definition, and if so, on what basis. They state that the ISAPP consensus definition is “the most actual definition”, the meaning of which is not clear to me, but then use an outdated definition in their summary box.

Further is the failure to acknowledge the broad scope of the definition of probiotics. Live biotherapeutic products (LBPs), which the paper states is a term that was “recently” introduced by the FDA, has been in use for over at least 15 years by the FDA’s Center for Biologics Evaluation and Research. The authors equate LBPs (which are defined as drugs) with next generation probiotics, yet these do not have to fall under the drug category any more than traditional probiotics are necessarily foods. Next generation probiotics, traditional probiotics or just probiotics can fall under numerous regulatory categories including foods, infant formulas, drugs, supplements, animal feeds, medical foods, foods for special dietary uses, and perhaps even cosmetics or medical devices. Thus, regulatory category is not stipulated by the definition, which is appropriate.

One of the difficulties with sorting through these terms is the lack of any consistent basis for defining them. Some terms, such as pharmabiotics and LBPs, are linked to specific regulatory categories. Others are defined by the nature of how they are comprised: live cells, cell components, or fermentation endproducts. Others are defined by their physiological benefit: psychobiotic, oncobiotic, immunobiotic. Even still, others are defined by their state of innovation: traditional vs. next generation probiotics. This state of affairs makes is impossible to develop a logical framework for categorizing them. Instead, we are left with a long list of substances that might be related, but have little real value. Where does it all stop? Next we will have to sift through thera/metabo/gen/retro/plas/func-biotics or any other pointless terms that can be arbitrarily slapped in front of ‘biotic.’

Certainly, there is nothing to prevent any person from coining a new term for a niche development. The many stakeholders in the broader ‘biotics’ field will, I suppose, determine any given term’s utility. I believe it would have been worthwhile for this paper to make an appeal to scientists to refrain from muddying the water by proposing new terms, and instead use existing terms with appropriate modifiers. For example, use ‘immune-active probiotic’ instead of ‘immunobiotic’, or ‘probiotic drug’ instead of ‘live biotherapeutic product.’ This approach is clearer to regulators and international organizations such as Codex Alimentarius, the US Food and Drug Administration and European Food Safety Authority. To the extent that the definitions of terms need to be clarified, I believe that the ISAPP approach, using groups of 10 or more well-known academic experts in the field reaching a consensus after extensive background search, is preferred over unilateral proclamations as delivered by this paper.

The Art of Interpretation

By Prof. Gregor Reid, BSc Hons PhD MBA ARM CCM Dr HS, Lawson Research Institute, University of Western Ontario, Canada

It takes a certain degree of intelligence to become a scientist, and certainly hard work to be able to fund a lab and students. Yet, is it not bemusing when scientists cannot interpret simple things like definitions and the results of human studies?

I’ve written repeatedly, as have others, about the definition of probiotics (in case you forgot – “Live microorganisms that, (or which) when administered in adequate amounts, confer a health benefit on the host”),1,2 and yet people look at it and must think that ‘dead’ fits, as does ‘consume’, as does ‘colonize’. It beggar’s belief how such a simple definition can be so badly interpreted by intelligent people.

Time after time papers I review mis-write and/or misinterpret the definition. Conference after conference, I hear dieticians, pharmacists, physicians, scientists not only get the definition wrong, but say things like ‘the probiotics in kombucha’ when there are none, ‘we have lots of probiotics in our gut’ when you don’t unless you consumed them, ‘the lactobacilli need to colonize’ when this was never a prerequisite nor does it happen except in rare instances.

The interpretation gets more difficult when people use terms that are completely undefined like ‘psycho-biotics’ and ‘post-biotics’. Even ‘dead probiotics’ have been used in clinical trials – God help us when the authors can’t even define it. Why stop at killing probiotic strains? Why not just kill any bacterial strain? Even the gut-brain axis which is now mentioned everywhere in the literature is undefined and unproven. The vagus nerve links to many body sites as does the nervous system, making it exceedingly difficult to prove that brain responses are only due to the gut microbes.

Everyone can site a manuscript that has been badly analyzed, interpreted or peer-reviewed, or whose findings are overblown. But let’s not excuse this as ‘it’s just science’ or ‘it’s just the way it is.’ No, it is not. When a paper uses a product that is stated to be ‘probiotic’, there is an onus on the authors to make sure the product meets the appropriate criteria. These have been stated over and over again and reiterated this March, 2019.3

If scientists and science writers are really that smart, then how do they keep getting this wrong? How do we let a poorly analyzed paper get published and allow authors to say that Bacteroides fragilis is a probiotic that can treat autism?4,5 And when this leads to companies claiming probiotics can treat autism, why do other scientists convey cynicism for the field instead of against their colleagues and specific companies making the false claims?

Where does opinion cross the line with ignorance or stupidity? Martin Luther King Jr. must have predicted life today when he said, “Nothing in all the world is more dangerous than sincere ignorance and conscientious stupidity.”

Is it envy or anger that drives the anti-probiotic sentiments? It seems to go far beyond a difference of opinion. When the BBC and JAMA fail to comment on two much better and larger studies on the effects of probiotics published6,7 at the same time as the ones in Cell8,9 that were promoted by press releases, what is driving opinion? The science or the press releases? Are the journalists and communications’ people interpreting study results vigorously? One cannot believe they are.

In an era where anyone can write anything at any time and pass it along to the world, what are we recipients to do? Just go with our instincts? Soon, we will not know the difference between fact and fake news. The avatars will be so real, we will act on falsehoods without knowing. When all news is fake, where does that leave us as people, never mind scientists?

Manuscripts are sent for peer-review but how many reviewers are experts in bioinformatics, molecular genetics, clinical medicine, biostatistics and what happens on the front line of products to consumers or patients? Like it or not, poor studies will get out there and it will be the media who will tell the story and interpret the findings or press releases.

One must hope that confirmatory science will continue and if it fails, the writers and readers will stop citing the original incorrect report. But how often does that happen? And what are we left with?

It takes effort to object or fight back, but if we don’t then the fake news will become the norm.

Try interpreting that if you will.

 

Literature Cited

  1.  FAO/WHO. 2001. Probiotics in food.  http://www.fao.org/food/food-safety-quality/a-z-index/probiotics/en/
  2. Hill C. et al. 2014. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotics. Nat. Reviews Gastroenterol. Hepatol. 11(8):506-14.
  3. Reid G. et al. 2019. Probiotics: reiterating what they are and what they are not. Front. Microbiol. 10: article 424.
  4. Hsiao et al. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 155(7):1451-63.
  5. Sharon G, et al. 2016. The central nervous system and the gut microbiome. Cell. 167(4):915-932.
  6. Korpela K. et al. 2018. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants. Microbiome. 6(1):182.
  7. De Wolfe, T.J. et al. 2018. Oral probiotic combination of Lactobacillus and Bifidobacterium alters the gastrointestinal microbiota during antibiotic treatment for Clostridium difficile infection. PLoS One. 13(9):e0204253.
  8. Suez J. et al. (2018). Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018 Sep 6;174(6):1406-1423.e16.
  9. Zmora N. et al. 2018. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. Sep 6;174(6):1388-1405.e21.
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.  

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.

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.

 

clinician_guides

Guides for use of probiotics in the clinic – some recent ISAPP initiatives

By Mary Ellen Sanders, PhD

At the ISAPP meeting earlier this month, Prof. Dan Merenstein, MD, presented a summary of recent ISAPP initiatives focused on helping translate the evidence of probiotics and prebiotics into clinical action.

A 2013 paper reported that 87% of hospital formularies surveyed in the United States carried at least one probiotic. Yet when Merenstein looked at the names of the products tested, many were not supported by evidence for such uses. This highlights the need for clinicians to have access to clear, evidence-based probiotic use guidelines.

ISAPP has worked through a variety of avenues to get information into the hands of clinicians. It has supported continuing education credit activities, webinars, collaboration with clinical organizations to develop guidelines, publications in clinical journals, presentations at clinical meetings, and simplified summaries using infographics and videos. Some examples include the following.

 

World Gastroenterology Organisation Global Guidelines – Probiotics and Prebiotics

This document is the most visited and downloaded of all WGO guidelines. In 2017, under the leadership of Prof. Francisco Guarner, MD PhD, this document was updated. Three current ISAPP board members were part of the process and ISAPP provided funding. See here.

 

Petitions

ISAPP petitioned the United States Preventive Services Task Force to examine the role of probiotics in preventing antibiotic-associated diarrhea. They considered the petition, but didn’t feel it fit their mission.

ISAPP petitioned American Academy of Family Physicians to consider reviewing the evidence for probiotics for AAD to include in their evidence-based guidelines. This is under consideration.

After attending 2017 ISAPP, Dr. Claire Merrifield BSc MBBS PhD led an effort to have NICE Clinical Knowledge Summaries mention probiotics for AAD in an effort to get local groups to adopt guidelines. This has met with limited success. See here.

 

CME or CE activities

On April 17, 2018, Merenstein and Mary Ellen Sanders PhD served as faculty for a CME-eligible webinar sponsored by Medscape on “Navigating the World of Probiotics. Helping Patients Make Good Choices”. The activity is available on Medscape’s website here.

In February 2018, Merenstein published a CE activity with the Pharmacy Times titled “The Expanding Health Benefits of Prebiotics and Probiotics”. See here

Upcoming in October 2018, Merenstein will present “Probiotics and the GI Tract. What Should a Busy Clinician Know” at the American Academy of Family Physicians Annual Conference. This conference is attended by over 4,000 physicians and is focused on clinical practice. The event, eligible for CME, will be recorded and made available after the live presentation.

ISAPP co-founder, Prof. Glenn Gibson has or will present 6 lectures over 2017 and 2018 on the topic of “The Learning Curve for Probiotics and Prebiotics.” These lectures are available for CME credit and are targeted to family doctors, gastroenterologists, pediatricians, and dieticians in the UK.

Numerous CME presentations over 2017-2018 have been given by ISAPP board members:

M.D. Cabana:

  • “Probiotics: Friend or Folly?”  American Academy of Pediatrics National Conference and Exhibition. Chicago, IL. September 17, 2017.  The audience was about 450-500 clinicians.
  • “Probiotics in Primary Care Pediatrics: Diarrhea, Colic & Eczema.” American Academy of Pediatrics California Chapter 1 Meeting. 300 clinicians
  • “Probiotics for Colic?” Zuckerberg San Francisco General Hospital. Department of Pediatrics Grand Rounds. San Francisco, CA.
  • “Probiotic Interventions for Colic” UCSF Benioff Children’s Hospital, Oakland.
  1. Reid:
  • “Effects and importance of microbiota on urogenital health in women.” 16th Annual Congress of Gynecology and Obstetrics, Antalya, Turkey. 300 obstetricians and gynecologists.
  • “Probiotics to whom for what?” Health World Ltd International Congress Natural Medicine 2017, Hunter Valley, New South Wales, Australia,.601 healthcare practitioners and naturopaths.
  • “The microbiome and how it relates to maternal/newborn care.” The Graham Chance Lectureship, Perinatal Research Day, London, ON. 100 neonatologists and pediatric experts.
  • “Microbes and the brain.” Integrative Healthcare Symposium, New York City. 500 naturopaths and various specialists.
  • “Probiotics and detoxification.” Environmental Health Symposium, Scottsdale, Arizona, 8th April. 500 naturopaths and various specialists.

 

Webinars

On June 28, ISAPP co-founder, Prof. Glenn Gibson, will present a webinar along with Profs. Ted Dinan and Ian Rowland titled “Why is everybody talking about gut microbiota?” Sponsored by the British Nutrition Foundation, this webinar will target healthcare professionals in the UK and Europe. See here.

 

Publications in clinical journals

Several ISAPP board members

  • Evidence-Based Probiotic Use in Family Medicine. Submitted, Journal of Family Practice. Merenstein/Sanders/Tancredi
  • Probiotics for Human Use. In press, Nutrition Bulletin. Sanders/Merenstein/Hutkins/Merrifield
  • Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Invited review in preparation, Nature Reviews Gastroenterology and Hepatology. Gibson/Reid/Sanders/Merenstein
  • Clinical perspectives of prebiotics and synbiotics. In preparation, Gastroenterology. Gibson/Quigley

 

Featured on ISAPPscience.org

Infographics

 

Videos

  • What is a probiotic?
  • Health benefits of probiotics
  • Are all probiotics the same?
  • How to choose a probiotic

 

General guidelines for choosing probiotics and prebiotics

Some initiatives that Merenstein championed were a direct result of ideas generated during the discussion group he led during the 2017 ISAPP meeting in Chicago.

 

Image courtesy of nursingschoolsnearme.com/
argentina_group

ISAPP board members share expertise in probiotic workshop in Buenos Aires

ISAPP board members, Prof. Seppo Salminen and Dr. Mary Ellen Sanders, along with over a dozen other renowned experts from the Southern Cone, Europe and Canada, participated in a workshop in Buenos Aires organized by Ricardo Weill of Instituto Danone Cono Sur April 26-27, 2018. The purpose of the workshop was two-fold. One goal was to share current science about probiotics with each other and with Codex Alimentarius and regulators from Argentina, to encourage a science-based approach to global probiotic standards that may end up with a draft of guidelines to be considered by the Codex Alimentarius late this year. Secondly, the intent is to convert each of the presentation topics into a chapter for a Spanish and English-language book to be published in the fall.

Two experts, Drs. Gabriel Vinderola and Rocio Martin, who participated in this meeting, will also serve as invited experts to the 2018 ISAPP meeting in Singapore June 5-6.

The concepts advanced by ISAPP in its papers on the scope and use of the term ‘probiotic’ and on the concept of core benefits and its regulatory implications were featured at this meeting. “The meeting was organized by Instituto Danone but it was devoid of all commercial content,” said Salminen.

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.

reid probiotics definition

You’d think we’d know probiotics by now

Prof. Gregor Reid, PhD MBA, Lawson Research Institute, University of Western Ontario, Canada

When I took my MBA, it was primarily to understand business and its relationship with science. I thought I learned quite a lot, but some things puzzle me to this day. Marketers know that messages are more effective when repeated. But, a guy called Thomas Smith (maybe related to Scotland’s famous Adam Smith who pioneered political economy, whatever that means!) wrote a guide in 1885 (yes that long ago!) called “Successful Advertising,” that noted:

The 1st time people see or read something, they don’t see it.
The 2nd time, they don’t notice it.
The 3rd time, they are aware that it is there.
The 4th time, they have a fleeting sense that they’ve seen it before.
The 5th time, they actually read the ad.
The 6th time, they thumb their nose at it.
The 7th time, they get a little irritated with it.
The 8th time, they think, “Here’s that confounded ad again.”
The 9th time, they wonder if they’re missing out on something.
The 10th time, they ask their friends or neighbors if they’ve tried it.
The 11th time, they wonder how the company is paying for all these ads.
The 12th time, they start to think that it must be a good product.
The 13th time, they start to feel the product has value.
The 14th time, they start to feel like they’ve wanted a product like this for a long time.

This goes on and on. It made me think about the definition and interpretation of probiotics. The version published in 2001 through two large respected organizations (WHO and UN FAO) has pretty much been universally accepted, and again reiterated in 2014 in a highly prestigious journal. That article is widely cited, so you’d think people would get it, right? They’d know what a probiotic is and what it’s not, right?

Yet, I speak at events around the world, and the same things keep coming back. Whether it is the 6th or 7th response (thumbing noses or being a little irritated) or a speaker confidently talking about probiotics and getting most of it completely wrong, I have scratched my head to the point my hair is falling out (a good research topic if someone would like to investigate this correlation). I even told a first year dentistry class of 55 students three times that the definition of probiotics would be an exam question. Only 8 got it correct!

I went back to the literature, as all scientists do, and asked the question “Why can’t people see what’s right in front of them?” It turns out either they believe you don’t have the answer, or you can’t have the answer, or you can’t have the answer right here and now, or they believe the answer needs to look like something else. This has a name – it’s called a schotoma – which seems appropriate, like people taking a shot at probiotics, or taking a shot at defining it, or providing their version of what it is.

With my hair now almost as thin as Glenn Gibson’s, I’m at a loss. Probiotics are not dead, not undefined/unstudied fermented foods, not in you unless you’ve taken them, not synonymous with “acidophilus”. They don’t typically colonize and they don’t have to be isolated from a human to work for humans. Products with lots of strains or a huge dose are not necessarily better products.

If you want to find the right probiotic for you, too often your doctor or health shop worker doesn’t give the best advice, because they haven’t read the articles. You should go www.usprobioticguide.com or www.probioticchart.ca and find something suitable for your needs. If you want some good general guidance, check out ISAPP infographics and ISAPP videos. If you are a company, don’t call your product a probiotic unless the contents have been tested in humans at the dose you are delivering at end of shelf-life. Call it strains of lactobacilli or something along those lines. Not being on one of these charts might be a sign that you’ve not done the needed work to call your product a probiotic.

But hey, maybe you need to read Thomas Smith’s guide. Probiotics are really quite simple. But, then again it’s only the hundredth time I’ve said that.

As for prebiotics, I’ll let someone else go bald on that one.

probiotics larson photo

Probiotics: the importance of the complete product

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.

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