Emerging per- and polyfluoroalkyl substances (PFAS) cause intestinal toxicity in marine medaka (Oryzias melastigma)

Perfluoroethylcyclohexane sulfonate (PFECHS) and 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA) are emerging per- and polyfluoroalkyl substances (PFAS) of growing concern due to their frequent detection in coastal environments and bioaccumulation in marine biota. Given structural similarities to legacy PFAS, it is hypothesized that these emerging PFAS may induce toxic effects on the digestive system in vivo. This study investigated the bioavailability and potential digestive damage of PFECHS and 6:2 Cl-PFESA using marine medaka (Oryzias melastigma) as a model animal. Fish were chronically exposed (90 days post-fertilization) to PFECHS and 6:2 Cl-PFESA at environmentally relevant concentrations (nominal: 0.1, 0.3, and 1.0 μg/L). Results demonstrated that 6:2 Cl-PFESA had a higher bioconcentration potential than PFECHS, and both emerging PFAS preferred accumulating in liver over intestines. PFECHS exposure caused alterations in intestinal digestive enzyme activities and substantial changes in intestinal microbial community in medaka. Compared with the 6:2 Cl-PFESA-exposure and control groups, PFECHS exposure decreased the relative abundance of beneficial bacteria (e.g., Bacteroides and Pseudomonas), while increased the relative abundance of Alkalimarinus and pathogenic bacteria Vibrio. Co-occurrence network analysis further revealed species interactions were less complex and cooperative in medaka exposed to PFECHS than 6:2 Cl-PFESA. These findings provide critical evidence for the toxic mechanisms of these emerging PFAS regarding their disruption of intestinal homeostasis, enzymatic function, and microbial symbiosis in marine fish.