Akkermansia muciniphila attenuates LPS-induced acute kidney injury by inhibiting TLR4/NF-κB pathway

Abstract

Acute kidney injury (AKI) is a global public health hazard with high morbidity and mortality. Sepsis accounts for nearly half of all causes of AKI. Scientists have made a great effort to explore effective therapeutic agents with limited side effects in the treatment of AKI, but have had little success. With the development of gut flora study, Akkermansia muciniphila (A. muciniphila) has been proven to prevent different organs by regulating the inflammatory response. However, the reno-protective function is still unknown. Here, the AKI model was induced using lipopolysaccharide (LPS) in mice with or without pretreatment of A. muciniphila. Renal function and histological change were measured. Inflammatory factors were detected by ELISA and rt-PCR. TLR4/NF-κB signaling factors and NLRP3 inflammasome were tested by western blot and immunohistochemistry. Pretreatment of A. muciniphila markedly inhibited inflammatory response and ameliorated kidney histopathological changes. Furthermore, the TLR4, p-NF-κB p65, and downstream IκBα were notably activated in the model group and inhibited by A. muciniphila. A similar effect was found in the regulation of NLRP3 inflammasome. In conclusion, pretreatment with A. muciniphila could protect against LPS-induced AKI by inhibition of the TLR4/NF-κB pathway and NLRP3 inflammasome activation. It may be a new therapeutic strategy for AKI prevention and treatment in the future.

Keywords: Akkermansia muciniphila; NLRP3 inflammasome; TLR4/NF-κB pathway; acute kidney injury; gut-kidney axis; lipopolysaccharide.