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Clostridium scindens attenuates acute kidney injury by producing indole-3-acetic acid
Yi-Zhi Cao1,2, Jiang-Yi Li1, Jun-Ming Hu1
1Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, China.
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.
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