Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease.
Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease.
复制标题
DOI：
10.1038/ncomms13419
复制
发表时间：
2016-11-23
影响因子：
16.6
通讯作者：
Stintzi, Alain
中科院分区：
文献类型：
--
作者：
Mottawea, Walid;Chiang, Cheng-Kang;Muelbauer, Marcus;Starr, Amanda E.;Butcher, James;Abujamel, Turki;Deeke, Shelley A.;Brandel, Annette;Zhou, Hu;Shokralla, Shadi;Hajibabaei, Mehrdad;Singleton, Ruth;Benchimol, Eric I.;Jobin, Christian;Mack, David R.;Figeys, Daniel;Stintzi, Alain
肠道微生物失调与克罗恩病(CD)有关。然而，导致慢性粘膜炎症的机制尚不清楚，这种炎症是该病的特征。在这份报告中，我们使用系统水平的方法来研究新发儿科患者肠道微生物区系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CD患者的宿主蛋白质组改变，表明线粒体功能受损。特别是，与硫化氢解毒有关的线粒体蛋白下调，而硫化氢微生物产生菌的相对丰度增加。网络相关分析表明，短杆拟青霉控制着硫化氢产生菌的中心枢纽。微小艾美耳球虫能诱导易患结肠炎的白介素10缺陷小鼠患上结肠炎，而这种表型需要肠道微生物区系的存在。给予硫化氢清除剂铋可减轻微小弧菌诱导的活体结肠炎。这项研究揭示了CD中宿主-微生物区系的相互作用受到干扰，从而为CD的发病机制提供了机制上的见解。克罗恩病与肠道微生物区系改变有关。在这里，作者证明了微生物微小顶杆菌与克罗恩病患者有关，在小鼠模型中引发结肠炎，并且清除微生物诱导的硫化氢改善了小鼠的症状。
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 H2S detoxification are downregulated, while the relative abundance of H2S microbial producers is increased. Network correlation analysis reveals that Atopobium parvulum controls the central hub of H2S producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the H2S 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. Crohn's disease is associated with altered intestinal microbiota. Here, the authors show that the microbe Atopobium parvulum is associated with Crohn's disease patients, triggers colitis in a mouse model, and that scavenging microbe-induced hydrogen sulfide improved symptoms in mice.
登录
查看更多内容
影响因子：
2.1
作者：
Hippe, Berit;Zwielehner, Jutta;Haslberger, Alexander G.
通讯作者：
Haslberger, Alexander G.
影响因子：
4.3
作者：
Faust K;Sathirapongsasuti JF;Izard J;Segata N;Gevers D;Raes J;Huttenhower C
通讯作者：
Huttenhower C
影响因子：
9.8
作者：
Kolho, Kaija-Leena;Korpela, Katri;de Vos, Willem M.
通讯作者：
de Vos, Willem M.
影响因子：
14.9
作者：
Cole JR;Wang Q;Cardenas E;Fish J;Chai B;Farris RJ;Kulam-Syed-Mohideen AS;McGarrell DM;Marsh T;Garrity GM;Tiedje JM
通讯作者：
Tiedje JM
DOI：
10.1126/science.1224820
发表时间：
2012-10-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arthur JC;Perez-Chanona E;Mühlbauer M;Tomkovich S;Uronis JM;Fan TJ;Campbell BJ;Abujamel T;Dogan B;Rogers AB;Rhodes JM;Stintzi A;Simpson KW;Hansen JJ;Keku TO;Fodor AA;Jobin C
通讯作者：
Jobin C