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ISAPP’s Guiding Principles for the Definitions of ‘Biotics’

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

Articulating a definition for a scientific concept is a significant challenge. Inevitably, scientists have different perspectives on what falls inside and outside the bounds of a term. Prof. Glenn Gibson, ISAPP co-founder and longtime board member, recently published a paper that describes his path to coining the word ‘prebiotic’, with this observation: “One thing I have learned about definitions is that if you propose one, then be ready for it to be changed, dismissed or ignored!”

Mary Ellen Sanders with Glenn Gibson

Members of the ISAPP board, however, have remained steadfast in their belief that such definitions are worth creating. They are the basis for shared understanding and coordinated progress across a scientific field.

Developing the consensus definition papers on probiotics, prebiotics, synbiotics, postbiotics and fermented foods was demanding on the part of all involved. The objective of the panels that met to discuss these definitions was clear – to provide common ground for consistent use of this growing body of terms for all stakeholders. Although some disagreement among the broader scientific community exists about some of the definitions, ISAPP’s approach relied on important, underlying principles:

  • Don’t unnecessarily limit future innovation
  • Don’t unnecessarily limit mechanisms of action
  • Don’t unnecessarily limit scope (host, regulatory category, mechanism, site of action, etc.)
  • Require a health benefit on a target host to be demonstrated – otherwise, what is the value of these biotic substances? (Of course, fermented foods were the exception in this criterion, because the value of consuming fermented foods even in the absence of an established health benefit is evident.)
  • Limit to preparations that are administered, not substances produced by in situ activities

In my opinion, many published definitions, including previous ones for postbiotics (see supplementary table here), are untenable because they don’t recognize these principles. There may also be a tendency to rely on historical use of terms, rather than to describe what is justified by current scientific knowledge. A good example of this is provided by the first definition of probiotics, published in 1965. It was “substances secreted by one microorganism that stimulate another microorganism” (Lily and Stillwell, 1965), which is far from the current definition of “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (Hill et al. 2014).

If you’re looking for a concise summary of the five published ISAPP definitions, see here for our definitions infographic.

Additional reflections: I noted with a smile Glenn’s views on ISAPP, specifically on the appropriate pronunciation of the abbreviation ‘ISAPP’. “My only negative is that everyone involved in the organisation aside from 2 or 3 of us pronounce its acronym wrongly.” Most board members, including myself, have always pronounced this as ‘eye-sap’. Glenn opines, “The abbreviation is not eye-SAPP, it is ISAPP (with the ‘I’ – remarkably enough – being spoken as it is in the word ‘International’).” I wonder how he pronounces IBM?

 

 

 

 

ISAPP’s 2021 year in review

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

The upcoming year-end naturally leads us to reflect about what has transpired over the past 12 months. From my perspective working with ISAPP, I witnessed ISAPP board members and the broader ISAPP community working creatively and diligently to find solutions to scientific challenges in probiotics, prebiotics and related fields. Let’s look back together at some of the key developments of 2021.

ISAPP published outcomes from two consensus panels this year, one on fermented foods and one on postbiotics. The popularity of these articles astounds me, with 49K and 29K accesses respectively, as of this writing. I think this reflects recognition on the part of the scientific community of the value – for all stakeholders – of concise, well-considered scientific definitions of terms that we deal with on a daily basis. If we can all agree on what we mean when we use a term, confusion is abated and progress is facilitated. The postbiotics definition was greeted with some resistance, however, and it will remain to be seen how this is resolved. But I think ISAPP’s response about this objection makes it clear that productive definitions are difficult to generate. Even if the field ultimately embraces another definition, it is heartening to engage in scientific debate about ideas and try to find alignment.

Keeping with the idea of postbiotics, a noteworthy development this year was the opinion from the European Food Safety Authority that the postbiotic made from heat-treated Akkermansia muciniphila is safe for use as a novel food in the EU. Undoubtedly, this development is a bellwether for likely future developments in this emerging area as some technological advantages to postbiotics will make these substances an attractive alternative to probiotics IF the scientific evidence for health benefits becomes available.

Recognizing the existing need for translational information for clinicians, ISAPP developed a continuing education course for dietitians. Published in March, it has currently reached close to 6000 dietitians. This course focused on probiotics, prebiotics and fermented foods: what they and how they might be applied in dietetic practice. It is a freely available, self-study course and completion provides two continuing education credits for dietitians.

On a sad note, in March of this year, ISAPP suffered the loss of Prof. Todd Klaenhammer. Todd was a founding ISAPP board member, and directed many of our activities over the course of his 18-year term on the board. He was also my dear friend and major advisor for my graduate degrees at NC State many years ago.  As one former collaborator put it, “I was not prepared to finish enjoying his friendship and mentorship.” See here for a tribute to Prof. Klaenhammer on the ISAPP blog: In Memoriam: Todd Klaenhammer.

So where will 2022 lead ISAPP? The organization has now published five consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods – extending its purview beyond where it started, with probiotics and prebiotics. Through the year ahead, ISAPP is committed to providing science-based information on the whole ‘biotics’ family of substances as well as fermented foods. Our Students and Fellows Association is growing, supported by the opportunity for young scientists to compete for the Glenn Gibson Early Career Researcher Prize. We continue to see our industry membership expand. Through our new Instagram account and other online platforms, our overall community is increasing. The ISAPP board of directors continues to evolve as well, with several long-term members leaving the board to make room for younger leaders in the field who will direct the future of the organization. This applies to me as well, as I have made the difficult decision to depart ISAPP in June of 2023. Thus, hiring a new executive director/executive science officer is an important priority for ISAPP in 2022. My 20 years with ISAPP have seen the organization evolve tremendously, through the hard work of incredible board members as well as many external contributors. We will strive to make 2022 – our 20th anniversary – ISAPP’s best year yet.

A roundup of the ISAPP consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods

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

ISAPP has long recognized the importance of precise definitions of the ‘biotic’ family of terms. As a scientific organization working to advance global knowledge about probiotics, prebiotics, synbiotics, postbiotics and fermented foods, we believe carrying out rigorous scientific studies—and comparing one result to another—is more difficult if we do not start with a clear definition of what we are studying.

Over the past 8 years, ISAPP has endeavored to bring clarity to these definitions for scientists and other stakeholders. ISAPP board members have met with other top experts representing multiple perspectives and specialties in the field to develop precise, useful and appropriate definitions of the terms probiotics, prebiotics, synbiotics, postbiotics and fermented foods. The definitions of these first four terms have all entailed the requirement that the substance be shown to confer a health benefit in the target host. Fermented foods have multitudes of sensorial, nutritional and technological benefits, which drive their utility. A health benefit is not required.

The problem with health benefits

The definitions provide significant advantages for the scientific community in terms of clarity but complexity arises when the same definitions are accepted by regulatory agencies. This requirement for a health benefit as part of the probiotic definition has been rigorously implemented in the European Union. Currently, with the exception of a few member states, the term probiotic is prohibited. The logic is that since a health benefit is inherent to the term probiotic and since there are no approved health claims for probiotics in the EU*, the term ‘probiotic’ is seen to be acting as a proxy for a health claim. This has frustrated probiotic product companies who believe they have met the scientific criteria for probiotics, yet cannot identify their product as a probiotic in the marketplace because they have not received endorsement of their claims by the EU. This is not an issue resulting from an unclear definition, since probiotics surely should provide a health benefit, but rather from a lack of agreement as to what level of evidence is sufficient to substantiate a health benefit.

ISAPP remains committed to the importance of requiring a health benefit for the ‘biotic’ family of terms (outlined in the table below). It’s clear that all of these definitions are meaningless unless the requirement that they confer a health benefit is considered as essential by all stakeholders. One could reasonably discuss whether the required levels of evidence for foods and supplements are too high in some regulatory jurisdictions, but the value of these substances collapses in the absence of a health benefit.

Summary of ISAPP consensus definitions

With the publication of the most recent ISAPP consensus paper, this one on postbiotics, I offer a summary below of the five consensus definitions published by ISAPP. Each definition is part of a comprehensive paper resulting from focused discussions among experts in the field and published in Nature Reviews Gastroenterology and Hepatology (NRGH). These papers are among the top most viewed of all time on the NRGH website and are increasingly cited by scientists and regulators.

Table. Summary of ISAPP Consensus Definitions of the ‘Biotics’ Family of Substances. Probiotics, prebiotics, synbiotics and postbiotics have in common the requirement for a health benefit. They may apply to any target host, any regulatory category and must be safe for their intended use. Fermented foods fall only under the foods category and no health benefit is required.

Definition Key features of the definition Reference
Probiotics Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Grammatical correction of the 2001 FAO/WHO definition.

No mechanism is stipulated by the definition.

 

Hill et al. 2014
Prebiotics A substrate that is selectively utilized by host microorganisms conferring a health benefit Prebiotics are distinct from fiber. Beneficial impact on resident microbiota and demonstration of health benefit required in same study. Gibson et al. 2017
Synbiotics A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host Two types of synbiotics defined: complementary and synergistic. Complementary synbiotics comprise probiotic(s) plus prebiotic(s), meeting requirements for criteria for each. Synergistic synbiotics comprise substrate(s) selectively utilized by co-administered live microbe(s), but independently, the components do not have to meet criteria for prebiotic or probiotic. Swanson et al. 2020
Postbiotics Preparation of inanimate microorganisms and/or their components that confers a health benefit on the host Postbiotics are prepared from live microbes that undergo inactivation and the cells or cellular structures must be retained. Filtrates or isolated components from the growth of live microbes are not postbiotics. A probiotic that is killed is not automatically a postbiotic; the preparation must be shown to confer a health benefit, as well as meet all other criteria for a postbiotic. Salminen et al. 2021
Fermented Foods Foods made through desired microbial growth and enzymatic conversions of food components Fermented foods are not the same as probiotics. They are not required to have live microbes characterized to the strain level nor have evidence of a health benefit. Types of fermented foods are many and are specific to geographic regions. Compared to the raw foods they are made from, they may have improved taste, digestibility, safety, and nutritional value. Marco et al. 2021

 

 

*Actually, there is one approved health claim in the EU for a probiotic: Scientific Opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

 

Further reading: Defining emerging ‘biotics’

definition

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

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

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

The webinar is now available here.