Akkermansia muciniphila Alleviates Persistent Inflammation, Immunosuppression, and Catabolism Syndrome in Mice

Many patients in intensive care units, especially the elderly, suffer from chronic critical illness and exhibit a new pathophysiological phenotype: persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Most patients with PICS have a constellation of digestive-system symptoms and gut failure. Akkermansia muciniphila (Akk) is a commensal gut bacterium that reduces inflammation, balances immune responses, modulates energy metabolism, and supports gut health. This study investigated the protective effects and underlying mechanisms of live and pasteurized Akk in treating PICS in a mouse model. PICS was induced on day 14 after performing cecal ligation and puncture (CLP) on day 1 and administrating lipopolysaccharide on day 11. Pasteurized or live Akk, or phosphate-buffered saline was administered twice daily by oral gavage for 7 days. Both live and pasteurized Akk attenuated PICS, as evidenced by reduced weight loss, and a reduction in symptoms and serum cytokine/chemokine levels. Liver and intestinal injuries were mitigated, and intestinal barrier integrity improved with Akk administration. Analysis of 16S rRNA amplicon sequences showed that Akk induced significant intestinal microbiota alterations, including increased abundance of Akk, Muribaculaceae, Parabacterbides goldsteinii, and decreased abundance of Escherichia_Shigella and Enterobacteriaceae. Collectively, Akk alleviates PICS by enhancing gut barrier function and reshaped the microbial community.