Clostridium scindens attenuates acute kidney injury by producing indole-3-acetic acid.

Abstract

The association between gut microbiota and acute kidney injury (AKI) has garnered increased attention recently. Herein, we investigated the effect of the gut microbiota and its metabolites on regulating AKI-associated kidney injury and inflammation. We observed that Clostridium scindens (CS) can ameliorate ischemia/reperfusion injury/folic acid-induced renal dysfunction, oxidative stress, and inflammation, and enhance intestinal barrier function. Mechanistically, CS can facilitate indole-3-acetic acid (IAA) production via the tryptophan metabolic pathway: tryptophan-indole-3-pyruvic acid-IAA. The increased intestinal IAA activates the aryl hydrocarbon receptor to restore intestinal barrier integrity and decreases interferon-γ influx into the bloodstream, thereby alleviating renal inflammation. The natural product Nobiletin ameliorated AKI by promoting CS growth. Our findings suggest that regulating CS is a promising approach for treating AKI.