基于多组学分析新型PFOA替代品—HFPO低聚体对小鼠肠道菌群的影响

近些年，六氟环氧丙烷低聚体 (HFPO-DA和HFPO-TA) 作为全氟辛酸 (PFOA) 替代品广泛应用于氟聚物制造业中。目前已在多种环境介质、动物及人体中被检出，对动物和人类有潜在的健康风险。长期低剂量暴露于某些环境化合物会导致肠道菌群组成和功能改变, 进而对宿主健康产生影响。目前，HFPO低聚体与肠道菌群之间的相互作用，及该作用是否与其诱导的毒性相关，尚不清楚。本项目拟利用宏基因组学、代谢组学和生物化学等技术手段，阐明HFPO-DA、HFPO-TA及PFOA刺激下小鼠肠道菌群结构及功能的变化，确定肠道菌群代谢产物的差异，并找出与之显著关联的菌株和代谢通路，解析肠道微生物在污染物暴露后诱导小鼠代谢紊乱中的作用，并比较HFPO同系物与PFOA毒性效应的差异。研究成果将为全面评估HFPO同系物的生态安全性提供新的科学证据，为全氟及多氟化合物 (PFASs) 的健康风险评估研究提供新的方向。

As an alternative to perfluorooctanoic acid (PFOA), oligomeric hexafluoropropylene oxide (HFPO-DA and HFPO-TA) has been increasingly used for fluoropolymer manufacture in recent years. Their growing detection in environmental matrices, wildlife and human raises considerable concern about its potential health risks. Numerous studies suggest long-term low-dosage exposure to certain environmental chemicals could change the composition and function of gut microbiota, and then produce different effects on host health. However, the alternation of gut microbiota and its relationship with host disorders after oligomeric HFPO exposure remain largely unknown. In the present study, techniques from metagenomics, metabolomics, and biochemistry are employed to (1) illustrate effects of oligomeric HFPO and PFOA on the composition and function of gut microbiota, (2) determined metabolism in feces that are significantly changed after chemicals exposure, and finding the related isolates and pathway, (3) explore the association between the alteration of gut microbiota and host liquid metabolism and (4) compared the toxic effects of oligomeric HFPO with PFOA. Our results will provide new evidence for fully assess the toxicology of oligomeric HFPO, and new options for studying the relationship between per- and polyfluoroalkyl substance (PFASs) and health risk.