Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5.
Nat Commun. 2016 Nov 23;7:13419. doi: 10.1038/ncomms13419.
Intestinal microbial dysbiosis is associated with Crohn's disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. In this report, we use systems-level approaches to study the interactions between the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms of disease. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. In particular, mitochondrial proteins implicated in HS detoxification are downregulated, while the relative abundance of HS microbial producers is increased. Network correlation analysis reveals that Atopobium parvulum controls the central hub of HS producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the HS scavenger bismuth mitigates A. parvulum-induced colitis in vivo. This study reveals that host-microbiota interactions are disturbed in CD and thus provides mechanistic insights into CD pathogenesis.
肠道微生物失调与克罗恩病（CD）有关。然而，导致这种疾病特征性慢性黏膜炎症的机制仍不清楚。在本报告中，我们使用系统水平的方法来研究新发儿科患者中肠道微生物群和宿主之间的相互作用，以评估疾病的因果关系和机制。我们报告了 CD 患者的宿主蛋白质组发生改变，表明线粒体功能受损。特别是，涉及 HS 解毒的线粒体蛋白下调，而 HS 微生物产生者的相对丰度增加。网络相关分析表明，短小普雷沃菌控制着 HS 产生者的中心枢纽。短小普雷沃菌在结肠炎易感白细胞介素-10 缺陷型小鼠中诱导全结肠炎，这种表型需要肠道微生物群的存在。给予 HS 清除剂铋可减轻体内短小普雷沃菌诱导的结肠炎。这项研究揭示了宿主-微生物群相互作用在 CD 中受到干扰，从而为 CD 的发病机制提供了机制见解。
