Inulin alleviates intestinal changes caused by gestational PFOA and GenX exposure in the offspring of mice through reshaping maternal gut microbiota and vertically inhibiting the TLR4/NF-κB/NLRP3 inflammatory pathway in the pups.

Ammonium perfluoro (2-methyl-3-oxahexanoate) (GenX) is one of short-chain alternatives of perfluorooctanoic acid (PFOA) and has emerged as persistent global environmental pollutant due to its resistance to degradation. Nonetheless, the effects and mechanisms of perinatal exposure to GenX or PFOA on both mothers and offspring enterohepatic system remain poorly understood. In this study, pregnant C57BL/6J mice were administered 1 mg/kg body weight (bw)/day of PFOA or 2 mg/kg bw/day of GenX until the fourth week postpartum, with or without an inulin intervention at 5 g/kg bw/day. The results indicated that GenX or PFOA exposure significantly induced liver injury, gut microbiota imbalance, and intestinal barrier damage in the dams, as well as caused liver function changes, increase in the intestinal permeability, and pyroptosis induction in the pups. Furthermore, inulin intervention mitigated intestinal toxicity in the pups by remodeling the gut microbiota composition in the dams and inhibiting the TLR4/NF-κB/NLRP3 inflammatory pathway in the pups. Taken together, this study elucidated that intestinal homeostasis imbalance induced by the perinatal GenX or PFOA exposure in the dams vertically mediated intestinal toxicity in the pups and highlighted the potential therapeutic role of inulin, contributing to a better understanding and management of environmental pollutant-induced health issue.