Influence of bisphenol A and its analogues on human gut microbiota composition and metabolic activity: Insights from an in vitro model.

Food contamination is a primary route of human exposure to bisphenols (BPs), which are known to affect gut microbiota (GM) and intestinal health. This study comprehensively assessed the impact of bisphenol A (BPA) and three of its substitutes-bisphenol S (BPS), bisphenol F (BPF), and tetramethyl bisphenol F (TMBPF, the monomer of valPure V70) - on the taxonomic and functional profile of human GM using an in vitro model. Human GM was acutely exposed to 1 mM concentrations of these BPs during a 48 h anaerobic cultivation. We first examined the effects of BPA, BPS, BPF, and TMBPF on GM taxonomic and metabolic profiles, mainly focusing on short-chain fatty acids (SCFAs) production. We then evaluated the degradation potential of these BPs by GM and its influence on their estrogenic activity. Finally, we assessed the impact of GM metabolites from BPs-exposed cultures on the viability of intestinal epithelial cells (Caco-2). BPA, BPS, and BPF severely disrupted GM taxonomic composition and metabolite profiles, significantly reducing SCFAs production. In contrast, TMBPF exhibited the least disruptive effects, suggesting it may be a safer alternative. Although the GM did not biotransform the BPs, bioadsorption occurred, with affinity correlating to hydrophobicity in the order of TMBPF > BPA > BPF > BPS. GM reduced the estrogenic activity of BPs primarily through bioadsorption. However, exposure of gut epithelial cells to Post-Culture Supernatants of BPA, BPF, and TMBPF significantly reduced Caco-2 cell viability, indicating the potential formation of harmful GM-derived metabolites and/or a depletion of beneficial GM metabolites.