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二恶英类多氯联苯 126(PCB126)通过激活芳香烃受体破坏小鼠肠道微生物群-宿主代谢功能障碍。

Dioxin-like polychlorinated biphenyl 126 (PCB126) disrupts gut microbiota-host metabolic dysfunction in mice via aryl hydrocarbon receptor activation.

机构信息

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Ecotoxicol Environ Saf. 2022 May 1;236:113448. doi: 10.1016/j.ecoenv.2022.113448. Epub 2022 Mar 31.

DOI:10.1016/j.ecoenv.2022.113448
PMID:35367886
Abstract

Exposure to environmental pollutants, including dioxin-like pollutants, can cause numerous health issues. A common exposure route to pollutants is through contaminated foods, and thus the gastrointestinal system and gut microbiota are often exposed to high amounts of pollutants. Multiple studies have focused on the imbalance in intestinal microbiota composition caused by dioxin-like pollutants. Here, we examined the effects of polychlorinated biphenyl 126 (PCB126) on the composition and functions of gut microbes through metagenomic sequencing, and explored the correlations between microflora dysbiosis and aryl hydrocarbon receptor (AHR) signaling. Adult male wild-type and Ahr mice with a C57BL/6 background were weekly exposed to 50 μg/kg body weight of PCB126 for 8 weeks. Results showed that PCB126 had the opposite effect on gut microbiota composition and diversity in the wild-type and Ahr mice. Functional prediction found that PCB126 exposure mainly altered carbon metabolism and signal regulatory pathways in wild-type mice but impacted DNA replication and lipopolysaccharide biosynthesis in Ahr mice. In wild-type mice, PCB126 exposure induced liver injury, decreased serum lipid content, and delayed gastrointestinal motility, which were significantly correlated to several specific bacterial taxa, such as Helicobacter. Following AHR knockout, however, the holistic effects of PCB126 on the host were lessened or abolished. These results suggest that PCB126 may disrupt host metabolism and gut microbiota dynamics via AHR activation. Overall, our findings provide new insight into the complex interactions between host metabolism and gut microbiota, which may contribute to grouped assessment of environmental pollutants in the future.

摘要

暴露于环境污染物,包括类二恶英污染物,会导致许多健康问题。污染物的常见暴露途径是通过受污染的食物,因此胃肠道系统和肠道微生物群经常暴露于大量的污染物中。多项研究集中在类二恶英污染物引起的肠道微生物群落组成失衡上。在这里,我们通过宏基因组测序研究了多氯联苯 126(PCB126)对肠道微生物组成和功能的影响,并探索了微生物群落失调与芳烃受体(AHR)信号之间的相关性。具有 C57BL/6 背景的成年雄性野生型和 Ahr 小鼠每周接受 50μg/kg 体重的 PCB126 处理 8 周。结果表明,PCB126 对野生型和 Ahr 小鼠的肠道微生物群落组成和多样性有相反的影响。功能预测发现,PCB126 暴露主要改变了野生型小鼠的碳代谢和信号调节途径,但影响了 Ahr 小鼠的 DNA 复制和脂多糖生物合成。在野生型小鼠中,PCB126 暴露诱导肝损伤、降低血清脂质含量并延迟胃肠道蠕动,这与几种特定细菌类群(如 Helicobacter)显著相关。然而,在 AHR 敲除后,PCB126 对宿主的整体影响减轻或消除。这些结果表明,PCB126 可能通过 AHR 激活破坏宿主代谢和肠道微生物群动力学。总的来说,我们的发现提供了宿主代谢和肠道微生物群之间复杂相互作用的新见解,这可能有助于未来对环境污染物进行分组评估。

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