Prenatal exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts the maternal gut microbiome and fecal metabolome homeostasis
Prenatal exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts the maternal gut microbiome and fecal metabolome homeostasis
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DOI：
10.1016/j.scitotenv.2023.169330
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发表时间：
2023-12-26
影响因子：
9.8
通讯作者：
Sheng，Nan
中科院分区：
文献类型：
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作者：
Shi，Guohui;Zhu，Bao;Sheng，Nan
六氟环氧丙烷三聚酸（HFPO-TA）最初被认为是全氟辛酸（PFOA）的“安全”替代品，多年来已广泛用于含氟聚合物的生产，导致其在环境中无处不在，随后发现其显著的生物累积特性和毒理学效应。然而，HFPO-TA对女性，特别是怀孕女性的具体影响仍不清楚。在本研究中，妊娠小鼠从妊娠第2天（GD）至GD 18天暴露于0.63 mg/kg/天HFPO-TA。然后，我们确定了GD 12（妊娠中期）和GD 18（妊娠晚期）暴露对肠道微生物群和粪便代谢物的潜在影响。我们的研究结果表明，除了肝损伤外，在指定窗口期间暴露于HFPO-TA还改变了盲肠肠道微生物群的结构和功能。值得注意的是，这些变化在GD 12和GD 18显示出相反的趋势。具体而言，在GD 12，HFPO-TA暴露主要导致拟杆菌门和变形菌门属内相对丰度的下调，以及相关的京都基因和基因组百科全书（KEGG）途径。随着暴露时间的延长，Proteobacteria中下调的属变得显著上调，伴随着人类疾病和炎症相关途径的相应上调，这表明HFPO-TA暴露可诱导肠道炎症并增加妊娠后期感染的风险。Pearson相关分析显示，肠道微生物群的紊乱伴随着异常的粪便代谢物。此外，与类固醇激素生物合成途径相关的激素在两个处死时间的变化表明，HFPO-TA暴露可能会改变孕鼠的类固醇激素水平，但需要进一步研究。总之，这项研究为HFPO-TA诱导的不良反应的机制提供了新的见解，并提高了对孕妇潜在持续健康风险的认识。
Initially considered a “safe” substitute for perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been extensively used in the production of fluoropolymers for several years, leading to its environmental ubiquity and subsequent discovery of its significant bio-accumulative properties and toxicological effects. However, the specific impact of HFPO-TA on females, particularly those who are pregnant, remains unclear. In the present study, pregnant mice were exposed to 0.63 mg/kg/day HFPO-TA from gestational day (GD) 2 to GD 18. We then determined the potential effects of exposure on gut microbiota and fecal metabolites at GD 12 (mid-pregnancy) and GD 18 (late pregnancy). Our results revealed that, in addition to liver damage, HFPO-TA exposure during the specified window altered the structure and function of cecal gut microbiota. Notably, these changes showed the opposite trends at GD 12 and GD 18. Specifically, at GD 12, HFPO-TA exposure primarily resulted in the down-regulation of relative abundances within genera from the Bacteroidetes and Proteobacteria phyla, as well as associated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. With extended exposure time, the down-regulated genera within Proteobacteria became significantly up-regulated, accompanied by corresponding up-regulation of human disease- and inflammation-associated pathways, suggesting that HFPO-TA exposure can induce intestinal inflammation and elevate the risk of infection during late pregnancy. Pearson correlation analysis revealed that disturbances in the gut microbiota were accompanied by abnormal fecal metabolite. Additionally, alterations in hormones related to the steroid hormone biosynthesis pathway at both sacrifice time indicated that HFPO-TA exposure might change the steroid hormone level of pregnant mice, but need further study. In conclusion, this study provides new insights into the mechanisms underlying HFPO-TA-induced adverse effects and increases awareness of potential persistent health risks to pregnant females.