Proton pump inhibitors alter the composition of the gut microbiota.
Proton pump inhibitors alter the composition of the gut microbiota.
复制标题
DOI：
10.1136/gutjnl-2015-310861
复制
发表时间：
2016-05
期刊：
影响因子：
24.5
通讯作者：
Steves CJ
中科院分区：
文献类型：
--
作者：
Jackson MA;Goodrich JK;Maxan ME;Freedberg DE;Abrams JA;Poole AC;Sutter JL;Welter D;Ley RE;Bell JT;Spector TD;Steves CJ
质子泵抑制剂（PPIs）是用于抑制胃酸分泌以及治疗胃肠道疾病（如消化性溃疡和胃食管反流）的药物。它们一直被认为风险较低，已被广泛使用，并且经常被过度处方。近期研究发现，使用它们会增加肠道及其他感染的风险。一些小型研究已经确定了PPI的使用与胃肠道微生物群之间可能存在关联，但这尚未在基于大规模人群的队列中进行研究。
我们利用1827名健康双胞胎的粪便样本进行16S核糖体RNA扩增，研究了PPI的使用与肠道微生物组之间的关联，并在一项干预性研究的未发表数据中重复了该结果。
我们发现PPI使用者的肠道共生菌丰度显著降低，微生物多样性也更低，同时口腔和上消化道共生菌的丰度显著增加。特别是在链球菌科中观察到显著增加。这些关联在一项独立的干预性研究以及70对在PPI使用上不一致的同卵双胞胎的配对分析中得到了重复验证。我们认为，观察到的变化是由于上消化道细菌和下消化道之间的低pH屏障被消除所致。
我们的研究结果描述了PPI对肠道微生物组的重大影响，应警惕PPI的过度使用，并需要进一步研究其作用机制及其临床后果。
Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort. We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study. We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut. Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences.