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.

六氟环氧丙烷二聚酸（HFPO-DA）是全氟辛酸（PFOA）的替代品，最近在世界范围内的环境水样中被检测到，具有多种毒性。然而，它是否会影响肠道和肠道微生物群尚不清楚。在本研究中，为了评估 HFPO-DA 在哺乳动物中的肠道毒性，雄性小鼠分别口服 0、2、20、200 μg/L HFPO-DA，持续 6 周。我们的结果表明，HFPO-DA 暴露引起结肠炎症，伴随着血清中 TNF-α 水平的增加和TNF-α、p65、TLR4、MCP-1 的mRNA 表达水平的增加。暴露于 200 μg/L HFPO-DA 后小鼠结肠的变化。我们还发现 HFPO-DA 暴露导致 MUC2 和 ZO-1 的 mRNA 表达水平和蛋白质水平降低，这意味着结肠肠道屏障功能障碍。在回肠，我们发现HFPO-DA暴露诱导各种炎症因子mRNA表达水平升高，但未发现屏障功能发生明显变化。此外，HFPO-DA 暴露导致盲肠肠道微生物群失衡和盲肠微生物群多样性变化。总之，所有这些结果表明 HFPO-DA 的潜在肠道毒性，并被认为是影响哺乳动物炎症、肠道屏障功能障碍和肠道微生物群紊乱的主要健康风险问题。