Safety of One of the Most Commonly Used Probiotic Strains: Systematic Review and Meta-analysis of Reported Adverse Events.

Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Probiotics are widely used in everyday foods and supplements but very few studies have thoroughly evaluated safety. We evaluated adverse events (AEs) for one of the most widely used strains, Bifidobacterium animalis subsp. lactis (BB-12). A systematic review (SR) and meta-analysis (MA) were conducted to evaluate adverse events in human trials using BB-12. Two independent reviewers separately searched for randomized controlled trials (RCTs) using the following mesh words for inclusion: English language, double-blinded, randomized or random allocation, and placebo-controlled trial of BB-12. One hundred and eighty-one studies were identified of which 35 qualified for inclusion. All authors of the 35 studies were contacted to perform an individual patient data meta-analysis (IPDMA). Results from the MA studies showed there was no statistical difference in the rates of AE between the probiotic (15.2%) and placebo (14%) groups, odds ratio = 1.10, 95% confidence interval (0.88, 1.36), p = .40. Further, results from the IPDMA showed statistically similar unadjusted (27% vs. 25%) and adjusted rates of AE (43% vs. 41%) between BB-12 and placebo, with the relative risk of AE being 1.05, 95% confidence interval (.94, 1.15). Both meta-analysis approaches showed no difference in the rates of AE for the BB-12 and placebo groups. The data support the safety of wide usage of BB-12. However, half of the RCTs analyzed for the MA did not report AE data. This is a major limitation of published literature. This study has been registered in PROSPERO: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023434556.