Perfluorooctane sulfonate (PFOS) is a persistent environmental chemical whose biological effects are mediated by multiple mechanisms. Recent evidence suggests that the gut microbiome may be directly impacted by and/or alter the fate and effects of environmental chemicals in the host. Thus, the aim of this study was to determine whether PFOS influences the gut microbiome and its metabolism, and the host metabolome. Four groups of male C57BL/6 J mice were fed a diet with or without 0.003 %, 0.006 %, or 0.012 % PFOS, respectively. 16S rRNA gene sequencing, metabolomic, and molecular analyses were used to examine the gut microbiota of mice after dietary PFOS exposure. Dietary PFOS exposure caused a marked change in the gut microbiome compared to controls. Dietary PFOS also caused dose-dependent changes in hepatic metabolic pathways including those involved in lipid metabolism, oxidative stress, inflammation, TCA cycle, glucose, and amino acid metabolism. Changes in the metabolome correlated with changes in genes that regulate these pathways. Integrative analyses also demonstrated a strong correlation between the alterations in microbiota composition and host metabolic profiles induced by PFOS. Further, using isolated mouse cecal contents, PFOS exposure directly affected the gut microbiota metabolism. Results from these studies demonstrate that the molecular and biochemical changes induced by PFOS are mediated in part by the gut microbiome, which alters gene expression and the host metabolome in mice.

中文翻译：

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全氟辛烷磺酸改变小鼠肠道微生物群-宿主代谢稳态。


全氟辛烷磺酸 (PFOS) 是一种持久性环境化学物质，其生物效应由多种机制介导。最近的证据表明，肠道微生物组可能直接受到环境化学物质在宿主体内的影响和/或改变其命运和影响。因此，本研究的目的是确定 PFOS 是否影响肠道微生物组及其代谢以及宿主代谢组。四组雄性 C57BL/6 J 小鼠分别喂食含有或不含 0.003%、0.006% 或 0.012% PFOS 的饮食。使用 16S rRNA 基因测序、代谢组学和分子分析来检查饮食中 PFOS 暴露后小鼠的肠道微生物群。与对照组相比，饮食中的全氟辛烷磺酸暴露导致肠道微生物群发生显着变化。膳食中的全氟辛烷磺酸还会引起肝脏代谢途径的剂量依赖性变化，包括涉及脂质代谢、氧化应激、炎症、TCA循环、葡萄糖和氨基酸代谢的途径。代谢组的变化与调节这些途径的基因的变化相关。综合分析还表明，全氟辛烷磺酸引起的微生物群组成的变化与宿主代谢特征之间存在很强的相关性。此外，使用分离的小鼠盲肠内容物，PFOS 暴露直接影响肠道微生物群代谢。这些研究的结果表明，全氟辛烷磺酸诱导的分子和生化变化部分是由肠道微生物组介导的，肠道微生物组改变了小鼠的基因表达和宿主代谢组。