Alistipes putredinis Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease in Rats via Gut Microbiota Remodeling and Inflammatory Suppression
Shuwei Zhang, Ruoshi Wang, R. Zhao, Yao Lu, Mingchao Xu, Xiaoying Lin, Ruiting Lan, Suping Zhang, Huijing Tang, Qianhua Fan, Jing Yang, Liyun Liu, Jianguo Xu
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver condition linked to obesity and metabolic imbalance. Alterations in the gut microbiota are increasingly recognized as contributors to its progression. Alistipes putredinis, a core member of the human gut microbiota, has been linked with metabolic health, but its functional role in MASLD remains unclear. Methods: This study evaluated the potential of A. putredinis strain Ap77, isolated from the stool of a healthy adult, to mitigate MASLD-related alterations in a high-fat diet (HFD)-induced rat model. Animals were divided into normal chow (NC), HFD, and HFD plus Ap77 groups and received daily oral gavage of Ap77 or PBS for 8 weeks. Results: Ap77 supplementation attenuated the body weight increase associated with high-fat diet consumption. It also reduced hepatic triglyceride levels and fat mass and improved liver histology. Transcriptomic analysis revealed suppression of inflammation-associated pathways. Correspondingly, the concentrations of IL-1β, IL-6, and TNF-α in both the liver and serum were reduced. Ap77 supplementation was associated with an increased abundance of health-associated bacterial genera, such as Lachnospiraceae UCG_010, Akkermansia, and Flavonifractor, as well as elevated serum levels of butyrate, indole-3-propionic acid, and indoleacrylic acid. Notably, correlation analysis revealed that Lachnospiraceae UCG_010 was positively associated with these metabolites. Conclusions: A. putredinis Ap77 alleviates hepatic steatosis and inflammation in MASLD, potentially by reshaping gut microbiota and suppressing inflammation-related signaling pathways.