Weissella viridescens Attenuates Hepatic Injury, Oxidative Stress, and Inflammation in a Rat Model of High-Fat Diet-Induced MASLD

<b>Background:</b> Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder globally. Probiotic supplementation has shown promise in its prevention and treatment. Although <i>Weissella viridescens</i>, a lactic acid bacterium with immunomodulatory effects, has antibacterial and anti-inflammatory activities, there is a lack of direct evidence for its role in alleviating MASLD. This study aimed to investigate the protective effects of <i>W. viridescens</i> strain Wv2365, isolated from healthy human feces, in a high-fat diet (HFD)-induced rat model of MASLD. <b>Methods:</b> Rats were randomly assigned to a normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with <i>W. viridescens</i> Wv2365 (Wv2365) groups. All groups were fed their respective diets for 8 weeks. During this period, the NC and HFD groups received a daily oral gavage of PBS, while the Wv2365 group received a daily oral gavage of Wv2365. <b>Results:</b> Wv2365 supplementation significantly reduced HFD-induced body weight gain, improved NAFLD activity scores, alleviated hepatic injury, and restored lipid metabolism. A liver transcriptomic analysis revealed the downregulation of inflammation-related pathways, along with decreased serum levels of TNF-α, IL-1β, IL-6, MCP-1, and LPS. Wv2365 also activated the Nrf2/HO-1 antioxidant pathway, enhanced hepatic antioxidant enzyme activities and reduced malondialdehyde levels. A gut microbiota analysis showed the enrichment of beneficial genera, including <i>Butyricicoccus</i>, <i>Akkermansia</i>, and <i>Blautia</i>. Serum metabolomic profiling revealed increased levels of metabolites including indole-3-propionic acid, indoleacrylic acid, and glycolithocholic acid. <b>Conclusions:</b> Wv2365 attenuates hepatic injury, oxidative stress, and inflammation in a rat model of high-fat-diet-induced MASLD, supporting its potential as a probiotic candidate for the modulation of MASLD.