Perfluorooctanoic acid exposure disrupts gut microbiota and aggravates experimental colitis.

Perfluorooctanoic acid (PFOA), a prevalent and environmentally persistent compound in the per- and polyfluoroalkyl substance (PFAS) family, is ubiquitously detected in the food chain and has been epidemiologically linked to inflammatory bowel disease (IBD). However, the actions and mechanisms by which PFOA exposure influences colonic inflammation under colitis conditions remain incompletely understood. In this study, we investigated the impact of dietary PFOA exposure on colitis severity using a dextran sulfate sodium (DSS)-induced colitis model. Our results suggest that dietary PFOA exposure exacerbated colitis severity, as reflected by increased loss in body weight, colon shortening, and histopathological damage. Notably, PFOA exposure promoted colonic neutrophil infiltration and activation, characterized by increased expression of neutrophil markers, upregulation of neutrophil-recruiting chemokines, and enhanced expression of oxidative enzymes. PFOA also led to goblet cell depletion and reduced E-cadherin expression in colitis mice, indicating compromised integrity of epithelial barrier. Furthermore, fecal microbiome and metabolomic analyses revealed that PFOA exposure altered gut microbial composition and fecal metabolic profiles, which could be associated with the enhanced inflammatory outcomes observed during acute colitis. Collectively, these findings indicate that dietary PFOA exposure aggravates experimental colitis through coordinated neutrophil-mediated inflammation, epithelial barrier disruption, and microbiome-associated alterations. Our results highlight the potential role of PFOA as an environmental exacerbator of IBD and provide mechanistic insight into how its exposure influences host-microbiome interactions.