Prenatal exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts the maternal gut microbiome and fecal metabolome homeostasis,Science of the Total Environment

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Prenatal exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts the maternal gut microbiome and fecal metabolome homeostasis
Science of the Total Environment ( IF 8.2 ) Pub Date : 2023-12-20 , DOI: 10.1016/j.scitotenv.2023.169330
Guohui Shi ₁ , Bao Zhu ₂ , Qi Wu ₁ , Jiayin Dai ₂ , Nan Sheng ₂

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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.

中文翻译：

产前接触六氟环氧丙烷三聚酸 (HFPO-TA) 会破坏母体肠道微生物组和粪便代谢组稳态

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，并随后发现其具有显着的生物累积性。性质和毒理学作用。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，怀孕小鼠从妊娠第 2 天到第 18 天暴露于 0.63 毫克/公斤/天的 HFPO-TA。然后我们确定了在第 12 天（妊娠第 12 天）时暴露对肠道微生物群和粪便代谢物的潜在影响。妊娠）和 GD 18（妊娠晚期）。我们的结果表明，除了肝脏损伤之外，特定窗口期间的 HFPO-TA 暴露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 时表现出相反的趋势。具体而言，在 GD 12 时，HFPO-TA 暴露主要导致拟杆菌门和变形菌门以及相关京都百科全书属内的相对丰度下调基因和基因组 (KEGG) 途径。随着暴露时间的延长，变形菌门内下调的属显着上调，并伴随着人类疾病和炎症相关途径的相应上调，这表明 HFPO-TA 暴露可诱发肠道炎症并增加感染风险怀孕后期。皮尔逊相关分析显示，肠道微生物群的紊乱伴随着异常的粪便代谢物。此外，两次处死时与类固醇激素生物合成途径相关的激素的变化表明，HFPO-TA暴露可能会改变怀孕小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 引起的不良反应的机制提供了新的见解，并提高了对怀孕女性潜在的持续健康风险的认识。

更新日期：2023-12-20

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