Bacillus subtilis pb2441 partially attenuates hepatic steatosis with transcriptomic changes broadly similar to dapagliflozin in a Western diet mouse model.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation accompanied by inflammation and fibrosis. While pharmacological interventions such as SGLT2 inhibitors have demonstrated clinical benefits, the potential of probiotic-based approaches remains under investigation. In this study, we evaluated the effects of Bacillus subtilis pb2441 in a Western diet (WD)-induced mouse model of NAFLD and compared its effects with dapagliflozin. WD feeding resulted in increased body weight, liver weight, hepatic lipid accumulation, and expression of inflammation-, fibrosis-, and lipid metabolism-related genes, including increased lipogenesis and reduced β-oxidation. Transcriptomic analyses showed that pb2441 reduced lipogenesis-related gene expression while restoring β-oxidation-associated genes relative to the WD group, albeit to a lesser extent than dapagliflozin. H&E and Oil Red O staining demonstrated WD-induced hepatic steatosis and lipid accumulation, both of which were partially attenuated by pb2441 and dapagliflozin. Hepatic triglyceride levels were also reduced in both treatment groups, with a statistically significant decrease observed in the dapagliflozin group. Integrative analyses demonstrated that hepatic lipid accumulation was positively associated with inflammation scores, fibrosis-related gene expression, and serum ALT levels. Together, these findings indicate that pb2441 partially attenuates WD-induced hepatic steatosis and associated transcriptional changes, with broadly similar effects to dapagliflozin.