Toxicological safety evaluation of pasteurizedAkkermansia muciniphila

Gut microorganisms are vital for many aspects of human health, and the commensal bacteriumAkkermansia muciniphilahas repeatedly been identified as a key component of intestinal microbiota. Reductions inA. muciniphilaabundance are associated with increased prevalence of metabolic disorders such as obesity and type 2 diabetes. It was recently discovered that administration ofA. muciniphilahas beneficial effects and that these are not diminished, but rather enhanced after pasteurization. PasteurizedA. muciniphilais proposed for use as a food ingredient, and was therefore subjected to a nonclinical safety assessment, comprising genotoxicity assays (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day toxicity study. For the latter, Han Wistar rats were administered with the vehicle or pasteurizedA. muciniphilaat doses of 75, 375 or 1500 mg/kg body weight/day (equivalent to 4.8 x 10(9), 2.4 x 10(10), or 9.6 x 10(10)A. muciniphilacells/kg body weight/day) by oral gavage for 90 consecutive days. The study assessed potential effects on clinical observations (including detailed arena observations and a modified Irwin test), body weight, food and water consumption, clinical pathology, organ weights, and macroscopic and microscopic pathology. The results of both in vitro genotoxicity studies were negative. No test item-related adverse effects were observed in the 90-day study; therefore, 1500 mg/kg body weight/day (the highest dose tested, equivalent to 9.6 x 10(10)A. muciniphilacells/kg body weight/day) was established as the no-observed-adverse-effect-level. These results support that pasteurizedA. muciniphilais safe for use as a food ingredient. ; Peer reviewed