Lack of genotoxicity and subchronic toxicity in safety assessment studies of Akkermansia muciniphila formulation

A powder formulation of viable <i>Akkermansia muciniphila</i> bacteria (AMUC) was evaluated in a 90-day repeated-dose toxicity study in rats and a battery of genotoxicity studies to evaluate AMUC as a food ingredient. All studies followed Organisation for Economic Co-operation and Development protocols (OECD TG 408, 471 473, 474). AMUC was administered to rats <i>via</i> gavage at 0, 500, 1000, and 2000 mg/kg body weight/day (equivalent to 0, 4.1 × 10¹⁰, 9.2 × 10¹⁰, and 1.64 × 10¹¹ CFU/kg body weight/day). No mortality or treatment-related adverse effects were reported in any endpoints that were attributed to AMUC consumption. No bacterial translocation of viable <i>A. muciniphila</i> from the intestinal tract was found to the liver, mesenteric lymph nodes, or blood. The no-observed-adverse-effect level was concluded to be the highest dose tested (2000 mg/kg body weight/day), approximately 1.64 × 10¹¹ CFU/kg body weight/day. AMUC (nonviable) was not mutagenic when examined in an <i>in vitro</i> bacterial reverse mutation assay and not clastogenic in an <i>in vitro</i> mammalian chromosomal aberration test. Viable AMUC was not genotoxic when evaluated in an <i>in vivo</i> mammalian cell micronucleus assay when administered at up to 1.64 ×10¹¹ CFU/kg body weight/day. These results confirm that AMUC is not toxic under the conditions of these studies.