Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria.
Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria.
复制标题
质子泵抑制剂会增加小鼠对肠道致病菌口腔感染的易感性。
DOI：
10.1007/s10620-017-4905-3
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Azuma T.
中科院分区：
文献类型：
--
作者：
1Yasutomi E;Hoshi N;Adachi S;Otsuka T;Kong L;Ku Y;Yamairi H;Inoue J;Ishida T;Watanabe D;Ooi M;Yoshida M;Tsukimi T;Fukuda S;Azuma T.
背景和目的质子泵抑制剂（PPI）是最常见的处方药之一。据报道，副作用包括肠道感染风险增加。假设PPI可增加对肠道病原体的易感性;然而，其潜在机制尚不清楚。本研究旨在探讨兰索拉唑（Lansoprazole，Laz）是否能增加小鼠对肠道致病菌的敏感性，并进一步探讨其作用机制。啮齿动物）。通过组织学和定量PCR测量的炎性细胞因子表达水平来评估肠道感染的建立。为了测试是否Laz改变肠道环境，影响易感性，肠道pH值，微生物群，代谢产物和免疫细胞分布进行了评估，通过pH值测量，16 S rRNA基因测序，代谢组学，流式细胞仪分析后Laz administration.ResultsColitis诱导与lessC。与对照组相比，鼠毒素处理的小鼠。我们发现C.给药后，鼠类可到达盲肠。Laz增加了胃的pH值，但没有增加肠道的pH值。它引起了肠道生态失调，改变了小肠的代谢物含量。但这些变化并没有导致免疫细胞分布的改变。啮齿类肿瘤增加的病原体到达感染部位。我们的研究结果表明，这是由于胃pH值的增加，使更多的经口肠道病原体通过胃，而不是因为肠道环境的变化。
Background and AimsProton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it.MethodsMice were administered Laz intraperitoneally once daily and orally infected withCitrobacter rodentium(C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration.ResultsColitis was induced with lessC. rodentiumin Laz-treated mice as compared with the controls. We found that increased numbers ofC. rodentiumcould reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution.ConclusionsLaz raised susceptibility toC. rodentiumas increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.