Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease. human gut metagenome

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.

肠道微生物群失调与克罗恩病（Crohn's Disease, CD）密切相关，但目前尚未明确引发该病标志性慢性黏膜炎症的具体机制。本研究采用系统级研究方法，针对新发儿科克罗恩病患者的肠道菌群与宿主间的相互作用展开探究，以解析该病的致病因果关系与潜在机制。研究发现，克罗恩病患者的宿主蛋白质组发生显著改变，提示线粒体功能受损；其中，参与硫化氢（H₂S）解毒过程的线粒体蛋白表达下调，而产硫化氢微生物的相对丰度则显著升高。网络关联分析结果显示，细小阿托波菌（Atopobium parvulum）是产硫化氢菌群的核心调控枢纽。进一步实验表明，细小阿托波菌可在结肠炎易感的白细胞介素-10缺陷型小鼠体内诱发全结肠炎，且该表型的出现依赖于肠道菌群的存在；给予硫化氢清除剂铋剂可在体内有效缓解细小阿托波菌诱导的结肠炎。本研究揭示了克罗恩病中宿主与菌群的相互作用紊乱现象，为克罗恩病的发病机制提供了深入的机制性见解。