Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut
Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut
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DOI：
10.1111/1462-2920.12934
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发表时间：
2016-05-01
影响因子：
5.1
通讯作者：
Van de Wiele, Tom
中科院分区：
文献类型：
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作者：
Allais, Liesbeth;Kerckhof, Frederiek-Maarten;Van de Wiele, Tom
炎症性肠病(IBD)是一种复杂的多因素疾病，其特征是宿主对改变的共生微生物群和粘液屏障功能障碍的不适当反应。吸烟是IBD最著名的环境风险因素。在这里，我们研究了慢性烟雾暴露对常规小鼠肠道微生物群、粘液层组成和免疫因子的影响。我们比较了烟雾暴露24周后暴露在烟雾中的小鼠和暴露在空气中的小鼠(n=12)。免疫测序法(n=6)和变性梯度凝胶电泳法(n=12)均显示烟雾暴露使结肠细菌活性和群落结构发生明显改变。有趣的是，Lachnospiraceae sp.观察大鼠结肠活动情况。吸烟组小鼠回肠Muc2和Muc3基因表达增加，远端结肠Muc4基因表达增加(n=6)。此外，我们还观察到回肠中Cxcl2的升高和干扰素-γ的降低，近端结肠中IL-6的升高和转化生长因子-β的降低。紧密连接基因表达无明显变化。我们推测，慢性烟雾暴露作为肠道中潜在的危险因素，其调节作用可能是由上皮粘液特征的改变以及微生物组分和免疫因素的变化所驱动的。
Inflammatory bowel diseases (IBD) are complex multifactorial diseases characterized by an inappropriate host response to an altered commensal microbiome and dysfunctional mucus barrier. Cigarette smoking is the best known environmental risk factor in IBD. Here, we studied the influence of chronic smoke exposure on the gut microbiome, mucus layer composition and immune factors in conventional mice. We compared smoke-exposed with air-exposed mice (n = 12) after a smoke exposure of 24 weeks. Both Illumina sequencing (n = 6) and denaturing gradient gel electrophoresis (n = 12) showed that bacterial activity and community structure were significantly altered in the colon due to smoke exposure. Interestingly, an increase of Lachnospiraceae sp. activity in the colon was observed. Also, the mRNA expression of Muc2 and Muc3 increased in the ileum, whereas Muc4 increased in the distal colon of smoke-exposed mice (n = 6). Furthermore, we observed increased Cxcl2 and decreased Ifn-gamma in the ileum, and increased Il-6 and decreased Tgf-beta in the proximal colon. Tight junction gene expression remained unchanged. We infer that the modulating role of chronic smoke exposure as a latently present risk factor in the gut may be driven by the altered epithelial mucus profiles and changes in microbiome composition and immune factors.