<i>Bacillus subtilis</i> pb2441 Ameliorates Hepatic Steatosis by Decoupling Liver and Fat Tissue Lipid Accumulation in a High-Fat Diet-Fed Mouse Model

Nonalcoholic fatty liver disease (NAFLD) is a global health issue, often associated with gut dysbiosis. In recent years, probiotics have gained attention as potential therapeutic agents for NAFLD. This study explored the effects of a single strain, <i>Bacillus subtilis</i> with high surfactin secretion, on C57BL/6 mice fed a high-fat diet (HFD), a model for NAFLD, for 13 weeks. We conducted efficacy assays over 13 weeks on liver fat accumulation and gut microbiome modulation. <i>Bacillus</i> supplementation reduced body weight gain and fat accumulation in the liver, but not in adipose tissues. This indicates a decoupling of hepatic and adipose lipid accumulation-meaning that lipid reduction occurred selectively in the liver, independent of changes in peripheral fat storage. Hepatic steatosis and liver enzyme levels were significantly improved. The supplementation largely maintained or amplified the bacterial abundance shifts caused by the HFD. Only seven-including <i>Lactobacillus</i>, <i>Akkermansia</i>, and <i>Romboutsia</i>-out of 53 bacterial genera which were significantly changed by HFD were restored to normal levels by the supplementation. These three genera are commonly regarded as beneficial for human health due to their roles in gut barrier integrity, immune modulation, and metabolic regulation. In contrast, despite these limited changes in bacterial composition, bacterial enzyme analysis suggested significant metabolic modulation by <i>Bacillus</i> supplementation. A single strain of <i>Bacillus subtilis</i>, instead of a mixture of multiple bacterial strains, can prevent hepatic steatosis without affecting fat tissue weight, underscoring its potential as a targeted therapeutic option through microbiome modulation of a few beneficial bacteria.