Exposure to hexafluoropropylene oxide dimer acid (HFPO-DA) disturbs the gut barrier function and gut microbiota in mice

Hexafluoropropylene oxide dimer acid (HFPO-DA) is the substitute for perfluoro octanoic acid (PFOA), and recently it has been detected in environmental water samples worldwide and has multiple toxicities. However, whether it will affect the intestines and gut microbiota remains unclear. In this study, in order to evaluate the gut toxicity of HFPO-DA in mammals, male mice were orally exposed to 0, 2, 20, 200 μg/L HFPO-DA, respectively, for 6 weeks. Our results showed that HFPO-DA exposure caused colonic inflammation which was coupled with increased TNF-α levels in serum and increased mRNA expression levels of TNF-α, p65, TLR4, MCP-1 of the colon in mice after exposure to 200 μg/L HFPO-DA. We also found that HFPO-DA exposure induced the decreased mRNA expression levels and protein levels of MUC2 and ZO-1, which means the dysfunction of gut barrier in the colon. In the ileum, we found that HFPO-DA exposure induced the increased mRNA expression levels of various inflammatory factors, but no obvious changes was found to barrier function. Additionally, HFPO-DA exposure caused the imbalance of cecal gut microbiota and changes of cecal microbiota diversity. Taken together, all these results indicate the potential gut toxicity of HFPO-DA and is perceived as a major problem of health risk that affects the inflammation, gut barrier dysfunction, and gut microbiota disturbance in mammals.