Subchronic exposure of environmentally relevant concentrations of F-53B in mice resulted in gut barrier dysfunction and colonic inflammation in a sex-independent manner.

F-53B (6:2 chlorinated polyfluorinated ether sulfonate) is currently recognized as a safe alternative to long-chain PFASs in China. However, an increasing number of studies have recently authenticated its biotoxicological effects. In this study, for evaluating the gut toxicity of F-53B in mammals, both female and male mice were orally exposed to 0, 1, 3, or 10 μg/L F-53B for 10 weeks. Our results showed that F-53B significantly accumulated in the colon, ileum and serum when exposed to 10 μg/L F-53B for 10 weeks. F-53B exposure not only increased the transcriptional levels of ion transport-related genes but could also interact with the CFTR protein directly. Interestingly, subchronic F-53B exposure also increased the transcription of mucus secretion-related genes, but the protein level of Muc2 decreased after F-53B exposure, indicating that there was a compensatory phenomenon after mucus barrier injury. Furthermore, F-53B exposure also induced colonic inflammation associated with gut microbiota dysbiosis in the colon. Taken together, our results indicated that the potential gut toxicity of F-53B and almost all of the changed parameters were significantly affected in both female and male mice, suggesting that F-53B could disturb the gut barrier without sex dependence in mice.