Institut National de la Recherche Agronomique (INRA), UR454 Microbiologie, Saint-Genès-Champanelle, France.
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Sci Rep. 2016 Dec 16;6:39399. doi: 10.1038/srep39399.
The intestinal microbiota of patients with constipated-predominant irritable bowel syndrome (C-IBS) displays chronic dysbiosis. Our aim was to determine whether this microbial imbalance instigates perturbation of the host intestinal mucosal immune response, using a model of human microbiota-associated rats (HMAR) and dextran sulfate sodium (DSS)-induced experimental colitis. The analysis of the microbiota composition revealed a decrease of the relative abundance of Bacteroides, Roseburia-Eubacterium rectale and Bifidobacterium and an increase of Enterobacteriaceae, Desulfovibrio sp., and mainly Akkermansia muciniphila in C-IBS patients compared to healthy individuals. The bacterial diversity of the gut microbiota of healthy individuals or C-IBS patients was maintained in corresponding HMAR. Animals harboring a C-IBS microbiota had reduced DSS colitis with a decreased expression of pro-inflammatory cytokines from innate, Th1, and Th17 responses. The pre-treatment of conventional C57BL/6 mice or HMAR with A. muciniphila, but not with Escherichia coli, prior exposure to DSS also resulted in a reduction of colitis severity, highlighting that the anti-inflammatory effect of the gut microbiota of C-IBS patients is mediated, in part, by A. muciniphila. This work highlights a novel aspect of the crosstalk between the gut microbiota of C-IBS patients and host intestinal homeostasis.
便秘型肠易激综合征(C-IBS)患者的肠道微生物群显示出慢性失调。我们的目的是使用人类微生物相关大鼠(HMAR)和葡聚糖硫酸钠(DSS)诱导的实验性结肠炎模型,确定这种微生物失衡是否会引发宿主肠道黏膜免疫反应的紊乱。对微生物群落组成的分析显示,与健康个体相比,C-IBS 患者中拟杆菌、罗斯伯里氏菌-真杆菌和双歧杆菌的相对丰度降低,肠杆菌科、脱硫弧菌属和主要的阿克曼氏菌属的相对丰度增加。健康个体或 C-IBS 患者的肠道微生物群的细菌多样性在相应的 HMAR 中得以维持。携带 C-IBS 微生物群的动物的 DSS 结肠炎减轻,固有免疫、Th1 和 Th17 反应的促炎细胞因子表达减少。在 DSS 暴露之前,用 A. muciniphila 预处理而非用大肠杆菌预处理常规 C57BL/6 小鼠或 HMAR,也会导致结肠炎严重程度降低,这突出表明 C-IBS 患者肠道微生物群的抗炎作用部分是由 A. muciniphila 介导的。这项工作强调了 C-IBS 患者的肠道微生物群与宿主肠道内稳态之间相互作用的一个新方面。