prepared by R&D Department at Pendulum Therapeutics
Akkermansia muciniphila is one of the most abundant single species in the healthy human gut, and is specifically adapted to the gut mucosal environment. A. muciniphila can utilize mucin as a sole source of carbon, nitrogen and energy. In turn, mucin foraging by A. muciniphila releases sugars and short-chain fatty acids, which can support the growth of other health-promoting gut microorganisms. This intimate association with the gut lining renders A. muciniphila poised to interact with the host and modulate host responses. Indeed, across various in vitro and in vivo models, administration of live or pasteurized A. muciniphila cells, as well as A. muciniphila-derived components (e.g. membrane components, secreted proteins) appears to exert significant effects on immune and metabolic regulation. Immunomodulation results from A. muciniphila-mediated decreases in gut barrier leakiness and restoration of the mucin layer, as well as the bacterium’s ability to directly influence innate and adaptive immune responses. Because increased intestinal permeability and chronic inflammation are markers of multiple diseases, A muciniphila supplementation shows promise across numerous health endpoints. In support of this, A. muciniphila is implicated in the regulation of host metabolism, and has been shown to prevent weight and fat mass gain as well as to improve host insulin resistance and counter host glucose and lipid dysregulation. These effects may be partially mediated by the ability of A. muciniphila to affect host endocrine function and signaling molecules (e.g. endocannabinoids). Pendulum has recently confirmed the safety and efficacy of A. muciniphila probiotic administration by a pilot study in overweight/insulin-resistant volunteers, as well as by a second clinical study in patients with type II diabetes, administered a multi-strain synbiotic formulation containing A. muciniphila. This review aims to synthesize mechanisms by which A. muciniphila exerts benefits for the host, and highlight its unique potential as a next-generation probiotic.