Transformation of Bisphenols by Gut Microbiota: Insights into Species-Specific Pathways and Toxicity Implications

The widespread use of bisphenols (BPs) in consumer products has raised significant concerns regarding their environmental fate and potential health impacts. The metabolic processes and transformation products (TPs) of BPs in vivo play a crucial role in determining their toxicological effects, with the gut microbiota serving as a key factor. However, studies on transformation of BPs by GM are scarce. In this study, we investigated the transformation of 21 BPs by six human gut bacterial strains in vitro. Among these, bisphenol A-glycerol methacrylate (Bis-GMA) was significantly transformed by different bacteria, and eight species-specific TPs were identified, including acetylated, ester-hydrolyzed, and palmitoylated products. In vivo studies further confirmed that Bis-GMA was converted into bisphenol A bis (2,3-dihydroxypropyl) ether (Bis-HPPP), the same product identified in vitro. Bis-HPPP exhibited a lower cytotoxicity than Bis-GMA in cytotoxicity assays. Furthermore, compared to Bis-HPPP, Bis-GMA induced more severe damage to human intestinal organoid function, including effects on apoptosis, cell proliferation, and the expression of key biomarkers. Overall, our findings provide valuable insights into the species-specific transformation of environmental contaminants by a human GM, highlighting the important role of microbial transformation in modulating toxicity of environmental pollutants.