International Scientific Association for Probiotics and Prebiotics releases statement about misleading conclusions from two studies published in the journal Cell

Two scientific papers were published last month in the high-impact journal Cell (here and here). The first one addressed the ability of particular strains of live microorganisms to colonize in both the mucosal microbiome and stool microbiome of mice and humans; the second focused on the ‘reconstitution’ of the microbiome and transcriptome after antibiotic treatment by particular probiotics and autologous fecal microbiome transplantation.

The board members of the International Scientific Association for Probiotics and Prebiotics (ISAPP), along with Drs. Francisco Guarner MD PhD and Bruno Pot PhD, have responded to these two papers and the accompanying press coverage with a critique recently published on the ISAPP website. The press coverage, including the Cell press release, came to conclusions regarding probiotic safety and efficacy in the absence of any human clinical endpoints. However, it is clinical endpoints, not microbiota outcomes, that drive the value of any probiotic product. By using such clinical endpoints, many well-conducted human studies (including those that comprise gold-standard evidence) have shown the efficacy and safety of different probiotic strains.

The clinical applicability of the findings is also called into question because, unlike how probiotics are typically used, the subjects in the study started taking the probiotics seven days after the antibiotic treatment began. Such a delay in probiotic dosing does not reflect clinical practice, does not mimic clinical trials, and may prevent the probiotic from having the intended effect.

Further concerns about the studies included:

  • The microbiome data analysis does not use a consistent method; nor is there an explanation about why they chose each method of analysis in each situation.
  • Why the authors chose to study the particular combination of strains is unclear, since there is no published evidence that the chosen probiotic has a clinical benefit for those taking antibiotics.
  • The authors suggest the novelty of their finding that probiotics may not colonize, when this is already well known in the scientific field.

On the other hand, the underlying question the Suez et al. study sought to address was a good one; we have scarce data on the impact of probiotics on a perturbed microbiota. One hypothesis of probiotic functionality is that probiotics promote gut homeostasis, a hypothesis that the Suez et al. study does not support. Further, the study is notable as the authors went beyond fecal samples, which most microbiome studies rely on, and collected mucosal and luminal samples from colonoscopy and deep endoscopy procedures from human subjects.

ISAPP recently put out a press release highlighting problems with the two papers and the attendant media coverage, as media organizations around the world published articles that erroneously took the two scientific studies to mean that probiotics are ‘useless’. The study authors also made misleading statements via the media, generalizing about probiotics as a class and extrapolating their results to probiotic efficacy, rather than restricting comment to the live microorganisms studied in the paper and their impact on the microbiome.

The ISAPP Board of Directors that released the statement includes: Prof. Seppo Salminen, PhD; Prof. Daniel Merenstein, MD; Prof. Robert Hutkins, PhD; Prof. Michael Cabana, MD MPH; Dr. Karen Scott, PhD; Prof. Colin Hill, PhD; Prof. Glenn Gibson, PhD; Prof Eamonn Quigley, MD; Prof. Gregor Reid, PhD, MBA; Prof. Sarah Lebeer, PhD; and a non-voting Executive Science Officer, Dr. Mary Ellen Sanders, PhD.

Read the ISAPP statement.

This article was prepared with files from science writer Kristina Campbell.

Mary Ellen Sanders
Mary Ellen Sanders
Mary Ellen Sanders is a consultant in the area of probiotic microbiology, with special expertise on paths to scientific substantiation of probiotic product label claims. Dr. Sanders served as the founding president of the International Scientific Association for Probiotics and Prebiotics (ISAPP) and is currently the organization’s Director of Scientific Affairs/ Executive Officer. This international, non-profit association of academic and industrial scientists is dedicated to advancing the science of probiotics and prebiotics (www.isapp.net). Through numerous written, oral and video pieces, including a website, www.usprobiotics.org, she strives to provide objective, evidence-based information on probiotics for consumers and professionals. Key activities include: Panels to determine GRAS status of probiotic strains ; member of the American Gastroenterological Association Scientific Advisory Board for AGA Center for Gut Microbiome Research and Education ; World Gastroenterology Organisation Committee preparing practice guidelines for the use of probiotics and prebiotics for GI indications (2008, 2011, 2014) ; working group convened by the FAO/WHO that developed guidelines for probiotics (2002).