The Degree of Helicobacter pylori-Triggered Inflammation Is Manipulated by Preinfection Host Microbiota

The Degree of Helicobacter pylori-Triggered Inflammation Is Manipulated by Preinfection Host Microbiota
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DOI:
10.1128/iai.00044-13
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发表时间:
2013-05-01
影响因子:
3.1
通讯作者:
Ottemann, Karen M.
Ottemann, Karen M.
中科院分区:
医学2区
文献类型:
--
作者:
Rolig, Annah S.;Cech, Cynthia;Ottemann, Karen M.

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幽门螺杆菌感染全球超过30亿人,是胃癌的主要危险因素。大多数感染H.幽门螺杆菌感染仅发展为无症状胃炎,然而,有些发展为溃疡或胃腺癌。我们证明了一个以前不受重视的参数影响H。幽门螺杆菌疾病的结果是感染前宿主微生物群的变化。利用小鼠模型,我们通过抗生素治疗改变了微生物群,发现这些改变导致H显着降低。幽门引发的炎症特别是,抗生素预处理降低了H.幽门感染对H.幽门螺杆菌显示出与未处理小鼠中的许多差异,包括显著更多的簇IV和XIVa梭菌属,已知细菌通过调节性T细胞群影响炎症。我们的研究结果表明,微生物群的组成,可能是梭菌属,导致H.通过改变CD4(+)T细胞向胃室的募集来抑制幽门螺杆菌感染。我们的研究结果表明,胃微生物群可用作诊断工具,以确定哪些患者有患严重疾病的风险。
Helicobacter pylori infects over 3 billion people worldwide and is the primary risk factor for gastric cancer. Most individuals infected with H. pylori develop only asymptomatic gastritis; however, some develop ulcers or gastric adenocarcinoma. We demonstrate that one previously unappreciated parameter influencing H. pylori disease outcome is variation in the preinfection host microbiota. Utilizing a mouse model, we altered the microbiota by antibiotic treatment and found that these alterations resulted in significantly lowered H. pylori-triggered inflammation. Specifically, antibiotic pretreatment reduced CD4(+)T-helper cells and Ifn gamma transcript levels in gastric tissue after H. pylori infection. The bacterial communities in mice with a reduced response to H. pylori displayed many differences from those in untreated mice, including significantly more cluster IV and XIVa Clostridium spp., bacteria known to influence inflammation via regulatory T cell populations. Our findings suggest that microbiota composition, perhaps Clostridium spp., contributes to the variable disease outcome of H. pylori infection by altering the recruitment of CD4(+) T cells to the gastric compartment. Our results suggest that gastric microbiota could be used as a diagnostic tool to determine which patients are at risk for developing severe disease.