S2150 Variable Adherence to the Accepted Definition of a Probiotic and Recommended Criteria for Probiotic Characterization in Highly Cited Clinical Trials

Introduction: Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host (ISAPP 2014), highlighting 3 essential components: the organism must remain viable, be administered in a dose that provides the desired benefit, and confer a measurable health benefit. To promote robust, uniform and reproducible standards in randomized clinical trials (RCTs) the following additional criteria for characterization have been proposed: genome level identification, quality control, demonstrated survival in the GI tract, safety, and biological plausibility (ISAPP 2018). We evaluated the level of adherence of highly cited clinical studies on probiotics to both the ISAPP definition and additional criteria. Methods: The Scopus library was searched for RCTs published between 2019-2024 using the keywords: probiotic, clinical trial, humans. The term “probiotic(s)” had to be included in the title/abstract. No restrictions on language, journal or country of origin. Studies on fecal microbiota transplantation, non-viable or engineered bacteria and fermented foods were excluded. Two independent reviewers evaluated all abstracts. In the event of disagreement, the full text was reviewed. Included publications (2006) were then ranked based on total citation count and the top 100 were analyzed. Results: The agreement between reviewers was good (Kappa 0.71). The number of citations ranged from 34-251. Eighty-seven percent of studies were on adults; 68% employed multi-strain preparations. Lactobacillus and Bifidobacterium spp. were the most studied. Twenty-three percent of products included prebiotics. While 97% of these probiotic studies provided evidence of a health benefit, only 76% defined the included bacterial strains at genome level, 77% included information on shelf-life/viability, and 79% provided information on the derivation of the dose employed. Of greatest concern, only 46% of the studies reported data on quality control and manufacturing steps to ensure absence of contaminants. All probiotics had been demonstrated to survive in the GI tract (human studies or animal models). While all probiotics used were considered safe, in most cases data were not available for the specific strains studied. Only 63% of the studies met all 3 ISAPP criteria. Conclusion: While international organizations have established essential criteria for defining probiotics, these are not uniformly adhered to in clinical trials, highlighting the need for a comprehensive assessment of these standards.