OBS Interferes with the Recovery of Intestinal Inflammation by Regulating the Gut Microbiota of Mice

Abstract

Per/polyfluoroalkyl substances (PFASs) have been confirmed to have negative health effects in animal models. As a novel alternative to legacy PFASs, sodium ρ-perfluorous nonenoxybenzenesulfonate (OBS) raises growing concerns over environmental exposure and biological toxicity. Herein, colitis models were constructed for exploring the toxicity of OBS in intestinal homeostasis during the recovery period. The results verified the gut toxicity of OBS, which increased serum interleukin-1β/6/17α/22 (IL-1β, IL-6, IL-17α, IL-22) levels, decreased colonic mucus secretion, and changed gut microbiota. During colitis recovery, no statistically significant difference was observed in colonic mucus secretion and related gene expression in dextran sulfate sodium-OBS (DSS-OBS) compared with the DSS; compared with the CON group, the unchanged mucus secretion and gene expression in DSS-OBS ghad still a statistically significant difference. It indicated that the intestinal barrier disruption did not worsen after the OBS exposure, but the recovery might be delayed. Moreover, OBS exposure significantly changed gut microbiota during the recovery period, suggesting that disrupted gut microbiota might be associated with the delay of OBS-mediated inhibition of intestinal barrier repair. Additionally, network toxicology analysis identified the action targets of OBS (including Nuclear Receptor Subfamily 1 Group I Member 2 (NR1I2), Solute Carrier Family 22 Member 5 (SLC22A5), Glutathione S-Transferase Pi 1 (GSTP1), etc.), which mediate gut microbiota disorder and intestinal barrier dysfunction, and serve as potential biomarkers for OBS-induced intestinal-related diseases. Collectively, OBS exhibits definitive gut toxicity. Although short-term OBS exposure did not exacerbate the progression of colitis, it delayed the recovery of intestinal function. Among, multiple target sites, coupled with the gut microbiota, commonly mediate the gut toxicity of OBS. It suggested that the potential health risks of OBS cannot be overlooked, and the relevant departments should strengthen the management and develop next-generation alternatives.