Akkermansia muciniphila attenuates sepsis-induced immunosuppression by shaping endotoxin-tolerant macrophage phenotypes

Abstract Sepsis is a life-threatening condition characterized by immunosuppression, largely mediated by endotoxin tolerance. Akkermansia muciniphila (AKK), a gut probiotic, has been shown to modulate immune responses. In this study, 16S rRNA sequencing revealed decreased AKK levels in immunosuppressed individuals. In vitro experiments using RAW 264.7 macrophages demonstrated that endotoxin tolerance induced an M2 phenotype, which was reversed by AKK treatment, promoting an M1 phenotype. Additionally, AKK enhanced bacterial clearance of Pseudomonas aeruginosa. In vivo, AKK administration alleviated immunosuppression in an endotoxin-tolerant mouse model by modulating macrophage phenotypes. These findings highlight AKK as a potential therapeutic candidate for sepsis-induced immunosuppression.