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

Background Sepsis, a life-threatening condition resulting from a dysregulated host response to infection, is a great menace to public health. One of the primary pathological features of sepsis is immunosuppression, which is largely mediated by endotoxin tolerance. Akkermansia muciniphila (AKK), a gut probiotic, is known to modulate host immune responses. There is a pressing need to explore its potential role in addressing sepsis-induced immunosuppression. Methods To assess the abundance of AKK in immunosuppressed and normal immune groups, 16S rRNA sequencing was conducted. This analysis helped to explore the correlation between immunosuppression and decreased AKK levels. Flow cytometry and ELISA were used to probe the effects of AKK on the phenotype of endotoxin-tolerant macrophages and to test its ability to clear Pseudomonas aeruginosa. An endotoxin-tolerant mouse model was employed to validate the role of AKK in alleviating sepsis-induced immunosuppression through its effects on macrophage phenotypes. Results In in vitro experiments, an endotoxin-tolerant macrophage model constructed using RAW 264.7 cells showed that endotoxin-tolerant macrophages tended to be of the M2 phenotype, as evidenced by a decrease in M1-type macrophages and an increase in M2-type macrophages. Further in vitro experiments showed that the addition of AKK preparations was able to reduce M2-type macrophages and increase M1-type macrophages, suggesting that AKK bacteria were able to induce a shift in endotoxin-tolerant macrophages from the M2 to the M1 phenotype. In animal experiments, the endotoxin tolerance model in mice treated with different AKK preparations further confirmed that AKK bacteria alleviated the immunosuppressive state of septic mice by modulating the phenotype of endotoxin-tolerant macrophages. Conclusion Our research underscores the crucial role of AKK in mitigating sepsis-induced immunosuppression by steering the phenotype of endotoxin-tolerant macrophages. This insight positions AKK as a promising candidate for therapeutic intervention, potentially leading to advancements in the management of sepsis.