Per- and polyfluoroalkyl substances (PFAS) disrupt gut microbiome composition and metabolism in metabolic syndrome: Evidence from a host-free in vitro colonic model

Metabolic syndrome (MetS) is a global health concern linked to metabolic abnormalities and increased risk of type 2 diabetes and cardiovascular disease. Recent studies suggest that exposure to per- and polyfluoroalkyl substances (PFAS) may contribute to MetS through alterations in gut microbiota and metabolism, but the underlying mechanisms remain unclear. This study aimed to investigate the effects of PFAS exposure on gut microbiota composition and metabolism in MetS using a three-stage, automated, computer-controlled in vitro Human Colonic Model (HCM) system. We introduced PFAS exposure to the gut microbiome in vitro at two concentrations (100 ng/mL and 1000 ng/mL) and analyzed microbial community structure using microbiome analysis, while changes in gut microbial metabolism were assessed through targeted and untargeted metabolomics. Our results showed that PFAS exposure significantly altered gut microbiota composition, with notable changes in key genera such as Morganella and Bilophila. Metabolomics analysis revealed an increase in short-chain fatty acid (SCFA) production at 1000 ng/mL of PFAS exposure, as well as significant alterations in other metabolites, including decreased acetophenone and taurocholic acid in both concentrations. These findings suggest that PFAS exposure may disrupt gut microbiota homeostasis and contribute to metabolic disturbances associated with MetS. This study highlights the need for further investigation into the mechanisms underlying PFAS-induced alterations in gut microbiota and their potential impact on human health.