What do we mean by ‘conferring a health benefit on the host’?

By Prof. Colin Hill, University College Cork, Ireland

Four of the Consensus definitions produced by ISAPP in recent years (see 1-4 below) finish with a similar wording, insisting that probiotics, prebiotics, synbiotics and postbiotics must confer a health benefit on the host”. This proviso was included to explicitly reinforce the fact that the raison d’etre for these interventions is that they must demonstrably improve host health. It would perhaps be wise to just stop there and leave the interpretation of what this really means to each individual reader. But that would not make for a very long blog and I am not very wise. Furthermore, it is useful to be more precise for scientific and regulatory purposes. At least two aspects seem to be open to elaboration; what is meant by ‘host’ and what is a ‘health benefit’? I will base my thoughts on the probiotic definition, but the logic should apply equally to all four health-based definitions.

Host. According to the Google dictionary a host is an animal or plant on or in which a parasite or commensal organism lives’. This means there are millions of potential host species on our planet, something that could potentially create confusion. For example, if a well characterised microbe (or microbes) is shown to provide a measurable health benefit when administered in adequate amounts in a murine model (the host) then it clearly meets the stated definition of probiotic. But only for mice! It should not be referred to as a probiotic for other species, including humans, solely based on murine evidence. This creates a situation where the same microbe can clearly meet the criteria to be a probiotic for one host but not for another. This is not simply semantics; it is of vital importance that it should not be assumed that health benefits confirmed in one host will also be realised in another without supporting evidence. Since the majority of discussions of probiotics address human applications, it may serve all stakeholders well – even if not directly mandated by the definition – if the word ‘probiotic’ was only used without qualification for microbes with measurable benefits in humans while all others should be qualified with the target host; ‘equine probiotic’, ‘canine probiotic’, or even ‘plant probiotic’.

Health benefit. Health is of course a continuum from a desirable but almost certainly unattainable state where every organ is performing optimally (something I will term ‘ideal health’) to a point where death is imminent (that I will term ‘poor health’). Of course, health is multidimensional and far more complex than a straight line between ‘ideal’ and ‘poor’ but for simplicity I will treat it as such. If we place ideal health on the left end of our straight line and poor health at the right end, then obviously any shift towards the left can be considered a health benefit. It could even be reasonably argued that if someone is gradually progressing from left to right down our imaginary line (for example, as we age) then halting or slowing down that progression could also be considered a health benefit. From this perspective every individual (not just the unwell) could potentially derive a health benefit from a probiotic, prebiotic, synbiotic or postbiotic.

The issue of cosmetic benefits is more nuanced. If an intervention improves someone’s appearance (or reduces body odour for example) it might not be considered a health benefit per se, but of course it could well have a beneficial effect on an individuals’ mental health. I will leave it to the psychologists and psychiatrists to determine how this could be convincingly demonstrated.

There is also the issue of production characteristics where the host is a food animal or a crop. If a microbial-based intervention leads to faster growth rates and increased yields should this qualify as a health benefit? My own opinion is if the intervention leads to higher productivity by preventing infections it could be considered a health benefit, but not if it simply leads to faster growth rates by improving feed conversion for example.

Can changing the microbiome be considered a health benefit? A trickier question is whether a direct effect on the microbiome could be considered as a health benefit? Every host has a microbiome of a particular configuration, richness, and diversity. I don’t think we are yet at a point where measurable changes in these general indices of microbiome composition can be termed a health benefit in the absence of a link to a more established health outcome. The consequence of any change will be microbiome-specific in any event; a reduction in diversity in the vaginal microbiome might be desirable, whereas an increase in diversity in the gut microbiome might well be considered beneficial. But what if we can measure a reproducible reduction in a specific pathobiont like Clostridioides difficile, or an increase in a microbe that is associated with good health such as Bifidobacterium? In my opinion we are arriving at a point where we can begin to refer to these impacts as a health benefit. This will become more and more relevant as we establish direct causal links between individual commensal microbes and health outcomes. Equally, an intervention that preserves microbiome structure during a disruption (e.g. infection or antibiotic treatment) could also be considered as beneficial. I don’t know if regulators are yet at the point of accepting outcomes such as these as direct health benefits, but I believe a strong case can be made.

To finish, I believe that it is a very exciting time for all of us in the field of probiotics, prebiotics, synbiotics and postbiotics, but it is really important that all of this important science is not compromised by loose language or by literal interpretations that adhere to the letter of the definitions but not to the intent. If you want to fully understand the intent of the definitions, I encourage you to read the full text of the consensus papers.



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.

Probiotics: Money Well-Spent For Some Indications

Eamonn M M Quigley MD, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA; Hania Szajewska MD, The Medical Univesrity of Warsaw, Department of Paediatrics, Poland; Dan Merenstein MD, Department of Family Medicine, Georgetown University

We read with interest and some concern the Medical News and Perspectives article by Jennifer Abbasi titled “Are Probiotics Money Down the Toilet? Or Worse?” (Abbasi 2019).  As researchers committed to the study of fecal microbiota transplant, prebiotics and probiotics, we find the title overly sensationalist for an article that ultimately provides a more nuanced view. It is unfortunate that the author focused on studies which either did not report on any clinical outcome and hence provide limited insight on the effectiveness of probiotics, or, whose null results likely reflect the late timing of the intervention while failing to refer to many high-quality studies that illustrate the subtlety of commensal and probiotic bacterial actions or clinical efficacy. Tanoue and colleagues provide a reminder that commensal engagement with the immune system is selective and precise (Tanoue et al. 2019). As Dr Knight points out, it would be surprising to witness the same response to any intervention in all individuals (Abbasi 2019). Efforts to individualize medical interventions, including probiotics, are worthwhile, but not yet realized. Until then, available evidence must be critically considered, but not ignored.  We wholeheartedly agree with the call for high quality clinical studies of probiotics but assert that it is also important to stress the challenges of performing clinical studies that seek to demonstrate clinical benefits in healthy human subjects; they require large study populations and are consequently very expensive. That clinical studies have been performed and demonstrated robust and clinically meaningful outcomes was illustrated by the study of Panigrahi where they demonstrated that an intervention comprising a probiotic plus prebiotic reduced sepsis among high-risk infants in rural India (Panigrahi et al. 2017). In the meantime, meta-analyses of smaller studies can provide insights into clinical benefit or harm. For example, systematic reviews and meta-analyses have consistently supported a role for probiotics in the prevention of Clostridium difficile–related illness, leading a JAMA review to state: “moderate-quality evidence suggests that probiotics are associated with a lower risk of C. difficile infection” (Goldenberg et al. 2018). Balanced with the low number needed to harm, probiotic interventions are attractive clinical options. We also question Abbasi’s focus on colonization as there is little, if any, evidence that this is necessary for probiotic activity.

We stress the obligation to provide a balanced view of the field which provides equal emphasis on successes as well as failures. No two probiotics (or probiotic cocktails) are alike; we should not expect they all have the same clinical impact.



  1. Abbasi J. Are probiotics money down the toilet? Or worse. JAMA 321(7):633-635. doi:10.1001/jama.2018.20798
  2. Tanoue T, Morita S, Plichta DR, et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019;565:600-605.
  3. Panigrahi P, Parida S, Nanda NC, et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017;548:407-412.
  4. Goldenberg JZ, Mertz D, Johnston BC. Probiotics to prevent Clostridium difficile infection in patients receiving antibiotics. JAMA 2018;320:499-450. 



Conflicts of interest:

All three authors are members of the Board of Directors of ISAPP

Eamonn M M Quigley holds equity in Alimentary Health and has served as a consultant to Alimentary Health, Allergan, Axon Pharma, Biocodex, Glycyx, Menarini, Pharmasierra, Salix and Vibrant.

Hania Szajewska reports no conflicts

Dan Merenstein has served as a consultant to Bayer, Debevoise & Plimpton, Pharmavite and Reckitt Benckiser