肠道菌群与宿主线粒体互作决定克罗恩病

Title：
Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease

DOI：
10.1038/ncomms13419

Abstract：
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.

All Authors：
Walid Mottawea,Cheng-Kang Chiang,Marcus Mühlbauer,Amanda E Starr,James Butcher,Turki Abujamel,Shelley A Deeke,Annette Brandel,Hu Zhou,Shadi Shokralla,Mehrdad Hajibabaei,Ruth Singleton,Eric I Benchimol,Christian Jobin,David R Mack,Daniel Figeys,Alain Stintzi

First Authors：
Walid Mottawea, Cheng-Kang Chiang, Marcus Mühlbauer

Correspondence：
Christian Jobin, David R Mack, Daniel Figeys & Alain Stintzi

内容要点：

1、系统水平研究肠道菌群与宿主的互作以阐释克罗恩病（CD）的发病原因和机制；

2、首次对新发儿科IBD患者开展肠粘膜-肠腔交界面肠道微生物菌群研究；

3、宿主蛋白质组的改变揭示线粒体功能受到损害；

4、发现Atopobium parvulum为CD严重程度的主要调节者；

5、揭示患者线粒体产生H2S与宿主对H2S的解毒之间平衡的改变。