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.