Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
Tokyo R&D Center, Miyarisan Pharmaceutical Co. Ltd., Saitama, Japan.
J Gastroenterol Hepatol. 2018 May;33(5):1059-1066. doi: 10.1111/jgh.14040. Epub 2018 Feb 14.
Acid suppressive agents including proton pump inhibitors (PPIs) are used as first-line treatment for various acid-related gastrointestinal disorders. Although known to profoundly reduce gastric acid production, their influence on inhibition of acid secretion as part of the function of the gastrointestinal tract microbiome remains to be elucidated. The aim of the present study was to examine the effects of PPI usage on oral and gut microbiota in healthy volunteers.
Ten healthy adult volunteers receiving no medications were enrolled. We obtained fecal, saliva, and periodontal pocket fluid samples from the subjects before and after 4 weeks of once daily administrations of 20-mg esomeprazole. The effects of PPI administration on bacterial communities were investigated using a 16S rRNA gene sequencing method.
Species richness (alpha diversity) was significantly different among the salivary, periodontal pocket, and fecal samples. Furthermore, the measurements for UniFrac distances, despite inter-individual variations (beta diversity), of the microbiota structure of saliva and periodontal pocket and feces samples were clearly separated from each other. The salivary samples showed significant differences between alpha and beta diversity measurements before and after administration of the PPI for 4 weeks. Meanwhile, taxon-based analysis indicated that PPI administration raised the ratio of Streptococcus organisms in fecal samples, suggesting a potentially unfavorable effect leading to gut microbiota alteration. Moreover, alterations of the microbiota in the oral carriage microbiome along with bacterial overgrowth (Streptococcus) and decreases in distinct bacterial species (Neisseria and Veillonella) were observed.
These results suggest that PPIs cause both oral and gut microbiota alterations.
质子泵抑制剂(PPIs)等抑酸剂被用作各种酸相关胃肠道疾病的一线治疗药物。尽管已知它们能显著减少胃酸的产生,但它们对胃肠道微生物组功能中胃酸分泌抑制的影响仍有待阐明。本研究旨在检查 PPI 使用对健康志愿者口腔和肠道微生物群的影响。
招募了 10 名未服用任何药物的健康成年志愿者。我们在这些志愿者接受每日一次 20mg 埃索美拉唑治疗 4 周前后,从他们身上获得粪便、唾液和牙周袋液样本。使用 16S rRNA 基因测序方法研究 PPI 给药对细菌群落的影响。
唾液、牙周袋和粪便样本之间的物种丰富度(alpha 多样性)存在显著差异。此外,尽管存在个体间变异(beta 多样性),但唾液和牙周袋及粪便样本的微生物结构的 UniFrac 距离测量值明显彼此分离。在接受 PPI 治疗 4 周前后,唾液样本的 alpha 和 beta 多样性测量值之间存在显著差异。同时,基于分类群的分析表明,PPI 给药增加了粪便样本中链球菌属生物体的比例,表明可能存在不利影响,导致肠道微生物群的改变。此外,观察到口腔携带微生物组中的微生物群发生改变,同时出现细菌过度生长(链球菌)和特定细菌物种(奈瑟菌和韦荣球菌)减少。
这些结果表明,PPIs 会引起口腔和肠道微生物群的改变。