BACKGROUND Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health. AIM To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease. METHODS A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria. RESULTS Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users). CONCLUSION PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.

中文翻译：

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系统评价：来自下一代测序研究的质子泵抑制剂对消化道证据微生物组的影响。

背景技术质子泵抑制剂（PPI）被广泛用于治疗上消化道的酸相关疾病。但是，大量的观察性研究引起了人们对与PPI相关的不良事件的担忧。近年来，来自下一代测序研究的数据表明，PPI影响肠道菌群的组成，而平衡的肠道微生物组对于维持健康至关重要。目的回顾下一代测序研究中有关PPI对肠道微生物组的作用的可用证据，并讨论PPI引起的营养不良对健康和疾病的潜在影响。方法按照系统评价和荟萃分析的首选报告项目的建议进行系统评价。一个PubMed查询产生197个结果。19个出版物符合预定的资格标准。结果该评价包括12个708个PPI用户的观察性研究队列和11个180个PPI用户的干预性研究队列。在大多数研究中，PPI治疗并没有影响微生物的丰富性和多样性，但与明显的分类学改变有关：在上消化道中，PPI使用者显示口腔衍生细菌的过度生长，主要是链球菌（基于六个独立队列的研究结果，其中126个PPI使用者）。在粪便样本中，PPI增加了芽孢杆菌（例如葡萄球菌科），乳杆菌（例如肠球菌科，乳酸杆菌，链球菌科）和放线菌科（例如放线菌科，微球菌科），巴斯德氏菌科和芽孢杆菌科的顺序中的多个分类。PPI减少的类群包括双歧杆菌科，Ruminococcaceae，Lachnospiraceae和Mollicutes（粪便样品中的发现基于19个独立队列，有790个PPI使用者）。结论PPI的使用与上，远端肠道菌群的适度改变有关。现有数据表明，PPI引起的胃酸过少会促进上消化道微生物群在消化道的更多远端部位定植。