Bisphenol M exposure promotes adiposity in mice via disrupting hepatic metabolism and gut microbiota homeostasis

Bisphenol M (BPM), a structural analog of bisphenol A (BPA) commonly used in food packaging and consumer plastics, remains incompletely characterized in terms of its obesogenic potential and underlying molecular mechanisms, posing challenges for evidence-based risk assessment. To address this gap, we investigated the obesogenic effects and metabolic impacts of BPM exposure in male BALB/c mice through integrated liver untargeted metabolomics and gut microbiome analysis. Our results showed that BPM exposure significantly increased body fat percentage, enlarged the epididymal white adipose tissue volume, and induced hepatic steatosis. Untargeted metabolomics revealed that BPM disrupted hepatic metabolic pathways, such as riboflavin metabolism, glycerophospholipid metabolism and fatty acid degradation. Concurrently, BPM altered gut microbiota, increasing the Firmicutes/Bacteroidetes ratio and abundances of Staphylococcus and Jeotgalicoccus . Correlation networks linked these microbial shifts to hepatic lipid metabolites, specifically implicating linoleic acid metabolism as a potential mediator of gut-liver crosstalk in obesity development. These findings indicate that BPM promotes adiposity through liver-gut crosstalk, advancing the understanding of obesogenic risks associated with BPA alternatives.