Lactobacillus gasseri LG-G12 Alleviates High-Fat Diet-induced Obesity through Gut Microbiota-Bile Acid Axis

Abstract The role of probiotics in weight management remains controversial. In this study, we found that Lactobacillus gasseri LG-G12 exhibits gut colonization capacity and metabolic regulation potential in vitro. In vivo, LG-G12 alleviated high-fat diet-induced weight gain and visceral fat accumulation in mice. Fecal targeted metabolomics identified bile acid metabolism as a key pathway. Furthermore, LG-G12 might exhibit bile salt hydrolase and hydroxysteroid dehydrogenase activities, contributing to a bile acid profile characterized by low cholic acid and high ursodeoxycholic acid levels. Additionally, LG-G12 increased the abundance of deoxycholic acid-producing Eubacterium spp., leading to elevated DCA levels. This distinct bile acid profile activated FXR and TGR5, reducing lipid accumulation and adipocyte differentiation in the liver and epididymal adipose tissue, and promoting thermogenesis in brown adipose tissue. Collectively, these findings demonstrate that LG-G12 ameliorates high-fat diet-induced obesity via the gut microbiota-bile acid axis, positioning LG-G12 as a promising candidate for weight management.