Unraveling the long-term gastrointestinal impact of perinatal perfluorobutane sulfonate exposure on rat offspring: Intestinal barrier dysfunction and Th17/Treg imbalance.

Per- and polyfluoroalkyl substances (PFAS), especially long-chain perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are increasingly acknowledged as a potential inflammatory bowel diseases (IBD) risk factor. Perfluorobutane sulfonate (PFBS), one kind of shorter chain alternative, has been reported to exhibit similar health hazards to those long-chain PFAS. However, the underlying mechanism underpinning PFBS-induced colonic inflammation has not been sufficiently elucidated. The T-helper-17 (Th17)/regulatory T (Treg) imbalance is a crucial event for the pathogenesis of colonic inflammation. In this study, we aimed to reveal whether and how perinatal PFBS exposure leads to the Th17/Treg imbalance and colonic inflammation in offspring. We firstly demonstrated in vivo that early-life PFBS exposure (0.5 mg/kg, 5 mg/kg) led to increased intestinal permeability and colonic inflammation accompanied by decreased expressions of tight junction protein 1 (Tjp1) and claudin-4 (Cldn4) and increased expressions of interleukin 17A (IL-17A) in colon of rat offspring. Further results indicated that PFBS exposure induces the Th17/Treg imbalance through upregulating the expression of retinoic acid receptor-related orphan receptor gamma t (Ror-γt) and transforming growth factor beta (TGF-β) and downregulating of forkhead box protein 3 (Foxp3) and IL-10 in colon. Moreover, metabolomics analyses indicated that bile secretion metabolism was significantly altered under PFBS exposure. The reduction of lithocholic acid and deoxycholic acid was closely related to the changes of TGF-β and IL-10 in colon, and may contribute to the perturbation of Th17/Treg balance and colonic inflammation. These results provide evidences for the immunotoxicity of PFBS and reveal the potential contribution to colonic inflammation, which raises concern on the health effects and risk assessment of short-chain PFAS.

Duke Scholars

Author Liping Feng Obstetrics and Gynecology, Reproductive Sciences