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Abstract：
Segmented filamentous bacteria (SFB) and Bacteroides fragilis are known to interact with the host immune response through the aryl hydrocarbon receptor (Ahr). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental toxicant and a high-affinity Ahr ligand has the potential to modify the effect of SFB and B. fragilis. MicroRNAs (miRNA) with their role in regulating gene expression post-transcriptionally, may potentially be used to observe such interactions between SFB, B. fragilis, and TCDD. However, little is known regarding the impact of gut microbial members on miRNA expression or its modulation in the presence of an environmental toxicant. This information is important in understanding toxicant-mediated dysbiosis in gut microbiome and the resulting human health impacts. In this study, C57BL/6 germ-free (GF) mice were colonized with SFB and B. fragilis and administered 30 μg/kg TCDD every 4 d for 28 d and miRNA were measured. Compared to GF mice, colonization with SFB resulted in an increase in up- and down-regulated Ileal miRNAs. TCDD treatment of this group decreased the number of upregulated miRNA and increased the number of down-regulated miRNAs. Association with SFB and B. fragilis together had a similar but less pronounced effect in response to TCDD treatment. TCDD treatment of GF mice had no miRNA expression response. Immune and inflammatory responses and T-cell differentiation were the key functions impacted by these miRNAs. Overall, these results reveal that the host response to toxicants may also depend on the presence of specific gut microbial populations.
摘要：
已知分段丝状细菌(SFB)和脆弱拟杆菌通过芳香烃受体(Ahr)与宿主免疫应答相互作用。2,3,7,8-四氯二苯并-对二恶英(TCDD)，环境毒物和高亲和力Ahr配体具有改变SFB和脆弱芽孢杆菌的作用的潜力。microRNAs（miRNA）在转录后调控基因表达中的作用，可能会被用来观察SFB之间的这种相互作用，B.脆弱，还有TCDD.然而,关于在环境毒物存在下肠道微生物成员对miRNA表达或其调节的影响知之甚少。这些信息对于了解肠道微生物组中有毒物质介导的菌群失调以及由此产生的人类健康影响非常重要。在这项研究中,用SFB和脆弱芽孢杆菌定植C57BL/6无菌（GF）小鼠，每4天施用30μg/kgTCDD，持续28天，并测量miRNA。与GF小鼠相比，用SFB定殖导致上调和下调回肠miRNA的增加。该组的TCDD处理减少了上调的miRNA的数量并增加了下调的miRNA的数量。与SFB和脆弱芽孢杆菌的联合在对TCDD治疗的反应中具有相似但不太明显的效果。TCDD处置GF小鼠无miRNA表达反响。免疫和炎症反应以及T细胞分化是受这些miRNA影响的关键功能。总的来说,这些结果表明，宿主对有毒物质的反应也可能取决于特定肠道微生物种群的存在。
