Alistipes putredinis Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease in Rats via Gut Microbiota Remodeling and Inflammatory Suppression

<b>Background:</b> 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. <i>Alistipes putredinis</i>, a core member of the human gut microbiota, has been linked with metabolic health, but its functional role in MASLD remains unclear. <b>Methods:</b> This study evaluated the potential of <i>A. putredinis</i> 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. <b>Results:</b> 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 <i>Lachnospiraceae UCG_010</i>, <i>Akkermansia</i>, and <i>Flavonifractor</i>, as well as elevated serum levels of butyrate, indole-3-propionic acid, and indoleacrylic acid. Notably, correlation analysis revealed that <i>Lachnospiraceae UCG_010</i> was positively associated with these metabolites. <b>Conclusions:</b><i>A. putredinis</i> Ap77 alleviates hepatic steatosis and inflammation in MASLD, potentially by reshaping gut microbiota and suppressing inflammation-related signaling pathways.