Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina; Department of Microbiology and Immunology, Chapel Hill, North Carolina.
Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina.
Cell Mol Gastroenterol Hepatol. 2021;12(4):1373-1389. doi: 10.1016/j.jcmgh.2021.06.017. Epub 2021 Jul 8.
BACKGROUND & AIMS: The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are caused in part by aberrant immune responses to resident intestinal bacteria. Certain dietary components, including carbohydrates, are associated with IBDs and alter intestinal bacterial composition. However, the effects of luminal carbohydrates on the composition and colitogenic potential of intestinal bacteria are incompletely understood. We hypothesize that carbohydrate metabolism by resident proinflammatory intestinal bacteria enhances their growth and worsens intestinal inflammation.
We colonized germ-free, wild-type, and colitis-susceptible interleukin-10 knockout mice (Il10) with a consortium of resident intestinal bacterial strains and quantified colon inflammation using blinded histologic scoring and spontaneous secretion of IL12/23p40 by colon explants. We measured luminal bacterial composition using real-time 16S polymerase chain reaction, bacterial gene expression using RNA sequencing and real-time polymerase chain reaction, and luminal glucosamine levels using gas chromatography-mass spectrometry.
We show that a consortium of 8 bacterial strains induces severe colitis in Il10 mice and up-regulates genes associated with carbohydrate metabolism during colitis. Specifically, Enterococcus faecalis strain OG1RF is proinflammatory and strongly up-regulates OG1RF_11616-11610, an operon that encodes genes of a previously undescribed phosphotransferase system that we show imports glucosamine. Experimental colitis is associated with increased levels of luminal glucosamine and OG1RF_11616 causes worse colitis, not by increasing E faecalis numbers, but rather by mechanisms that require the presence of complex microbiota.
Further studies of luminal carbohydrate levels and bacterial carbohydrate metabolism during intestinal inflammation will improve our understanding of the pathogenesis of IBDs and may lead to the development of novel therapies for these diseases.
炎症性肠病（IBD），包括克罗恩病和溃疡性结肠炎，部分是由对常驻肠道细菌的异常免疫反应引起的。某些膳食成分，包括碳水化合物，与 IBD 有关，并改变肠道细菌组成。然而，肠道内碳水化合物对肠道细菌的组成和致结肠炎潜力的影响尚不完全清楚。我们假设常驻炎症性肠道细菌的碳水化合物代谢增强了它们的生长并加重了肠道炎症。
我们用一组常驻肠道细菌菌株定植无菌、野生型和易患结肠炎的白细胞介素 10 基因敲除（Il10）小鼠，并使用盲法组织学评分和结肠外植体自发分泌白细胞介素 12/23p40 来量化结肠炎症。我们使用实时 16S 聚合酶链反应测量腔内细菌组成，使用 RNA 测序和实时聚合酶链反应测量细菌基因表达，使用气相色谱-质谱法测量腔内氨基葡萄糖水平。
我们表明，由 8 种细菌组成的联合体在 Il10 小鼠中引起严重的结肠炎，并在结肠炎期间上调与碳水化合物代谢相关的基因。具体而言，粪肠球菌 OG1RF 株是促炎的，并强烈上调 OG1RF_11616-11610，该操纵子编码一个以前未描述的磷酸转移酶系统的基因，我们表明该系统导入氨基葡萄糖。实验性结肠炎与腔内氨基葡萄糖水平升高有关，OG1RF_11616 导致更严重的结肠炎，不是通过增加粪肠球菌数量，而是通过需要复杂微生物群存在的机制。
进一步研究肠道炎症期间腔内碳水化合物水平和细菌碳水化合物代谢将提高我们对 IBD 发病机制的理解，并可能为这些疾病的新疗法的发展提供依据。
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