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芳烃受体的表达有助于小鼠肠道微生物群落结构的建立。

Expression of the aryl hydrocarbon receptor contributes to the establishment of intestinal microbial community structure in mice.

作者信息

Murray Iain A, Nichols Robert G, Zhang Limin, Patterson Andrew D, Perdew Gary H

机构信息

Center for Molecular Toxicology &Carcinogenesis Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA-16802, USA.

Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA-16802, USA.

出版信息

Sci Rep. 2016 Sep 23;6:33969. doi: 10.1038/srep33969.

Abstract

Environmental and genetic factors represent key components in the establishment/maintenance of the intestinal microbiota. The aryl hydrocarbon receptor (AHR) is emerging as a pleiotropic factor, modulating pathways beyond its established role as a xenobiotic sensor. The AHR is known to regulate immune surveillance within the intestine through retention of intraepithelial lymphocytes, functional redistribution of Th17/Treg balance. Consequently, environmental/genetic manipulation of AHR activity likely influences host-microbe homeostasis. Utilizing C57BL6/J Ahr and Ahr co-housed littermates followed by 18 days of genotypic segregation, we examined the influence of AHR expression upon intestinal microbe composition/functionality and host physiology. 16S sequencing/quantitative PCR (qPCR) revealed significant changes in phyla abundance, particularly Verrucomicrobia together with segmented filamentous bacteria, and an increase in species diversity in Ahr mice following genotypic segregation. Metagenomics/metabolomics indicate microbial composition is associated with functional shifts in bacterial metabolism. Analysis identified Ahr-dependent increases in ileal gene expression, indicating increased inflammatory tone. Transfer of Ahr microbiota to wild-type germ-free mice recapitulated the increase Verrucomicrobia and inflammatory tone, indicating Ahr-microbial dependence. These data suggest a role for the AHR in influencing the community structure of the intestinal microbiota.

摘要

环境和遗传因素是肠道微生物群建立/维持的关键组成部分。芳烃受体(AHR)正成为一种多效性因子,其调节途径超出了作为外源性物质传感器的既定作用。已知AHR通过保留上皮内淋巴细胞、Th17/Treg平衡的功能重新分布来调节肠道内的免疫监视。因此,对AHR活性的环境/遗传操纵可能会影响宿主-微生物的稳态。利用C57BL6/J Ahr和Ahr同窝饲养的小鼠,随后进行18天的基因分型分离,我们研究了AHR表达对肠道微生物组成/功能和宿主生理的影响。16S测序/定量PCR(qPCR)显示,门丰度有显著变化,特别是疣微菌门和分节丝状细菌,基因分型分离后Ahr小鼠的物种多样性增加。宏基因组学/代谢组学表明微生物组成与细菌代谢的功能转变有关。分析确定Ahr依赖性回肠基因表达增加,表明炎症状态增加。将Ahr微生物群转移到野生型无菌小鼠中,重现了疣微菌门增加和炎症状态,表明Ahr与微生物的依赖性。这些数据表明AHR在影响肠道微生物群的群落结构中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc46/5034278/2236ddc829a3/srep33969-f1.jpg

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