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

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

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

/in featured, News /by Mary Ellen Sanders

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

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

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

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

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

/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.

probiotics larson photo

 

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