Persistent organic pollutants (POPs) are important environmental chemicals and continued study of their mechanism of action remains a high priority. POPs, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), and polychlorinated biphenyls (PCBs), are widespread environmental contaminants that are agonists for the aryl hydrocarbon receptor (AHR). Activation of the AHR modulates the gut microbiome community structure and function, host immunity, and the host metabolome. In the current study, male C57BL6/J mice were exposed, via the diet, to 5 µg/kg body weight (BW) TCDF or 24 µg/kg BW of TCDF every day for 5 days. The functional and structural changes imparted by TCDF exposure to the gut microbiome and host metabolome were explored via 16S rRNA gene amplicon sequencing, metabolomics, and bacterial metatranscriptomics. Significant changes included increases in lipopolysaccharide (LPS) biosynthesis gene expression after exposure to 24 µg/kg BW of TCDF. Increases in LPS biosynthesis were confirmed with metabolomics and LPS assays using serum obtained from TCDF-treated mice. Significant increases in gene expression within aspartate and glutamate metabolism were noted after exposure to 24 µg/kg BW of TCDF. Together, these results suggest that after exposure to 24 µg/kg BW of TCDF, the gut microbiome increases the production of LPS and glutamate to promote localized gut inflammation, potentially using glutamate as a stress response.

中文翻译：

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小鼠肠道微生物组对持久性有机污染物2,3,7,8-四氯二苯并呋喃的反应的超转录组学分析。

持久性有机污染物（POPs）是重要的环境化学物质，对其作用机理的持续研究仍然是当务之急。持久性有机污染物，例如2,3,7,8-四氯二苯并-对-二恶英（TCDD），2,3,7,8-四氯二苯并呋喃（TCDF）和多氯联苯（PCB），是广泛的环境污染物，是持久性有机污染物的激动剂。芳基烃受体（AHR）。AHR的激活调节肠道微生物组的结构和功能，宿主免疫力和宿主代谢组。在当前的研究中，通过饮食使雄性C57BL6 / J小鼠每天暴露于5 µg / kg体重（BW）TCDF或24 µg / kg BW的TCDF中，持续5天。通过16S rRNA基因扩增子测序，代谢组学，和细菌的转录组学。显着变化包括暴露于24 µg / kg体重的TCDF后脂多糖（LPS）生物合成基因表达的增加。使用从TCDF处理过的小鼠获得的血清，通过代谢组学和LPS分析证实了LPS生物合成的增加。暴露于24 µg / kg体重的TCDF后，发现天冬氨酸和谷氨酸代谢中的基因表达显着增加。总之，这些结果表明，暴露于24 µg / kg体重的TCDF后，肠道微生物组会增加LPS和谷氨酸的产生，从而促进局部肠道炎症，可能利用谷氨酸作为应激反应。使用从TCDF处理过的小鼠获得的血清，通过代谢组学和LPS分析证实了LPS生物合成的增加。暴露于24 µg / kg体重的TCDF后，发现天冬氨酸和谷氨酸代谢中的基因表达显着增加。总之，这些结果表明，暴露于24 µg / kg体重的TCDF后，肠道微生物组会增加LPS和谷氨酸的产生，从而促进局部肠道炎症，可能利用谷氨酸作为应激反应。使用从TCDF处理过的小鼠获得的血清，通过代谢组学和LPS分析证实了LPS生物合成的增加。暴露于24 µg / kg体重的TCDF后，发现天冬氨酸和谷氨酸代谢中的基因表达显着增加。总之，这些结果表明，暴露于24 µg / kg体重的TCDF后，肠道微生物组会增加LPS和谷氨酸的产生，从而促进局部肠道炎症，可能利用谷氨酸作为应激反应。