Clinical Trials and Research Unit, Changi General Hospital, Singapore.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Singapore Med J. 2019 Oct;60(10):512-521. doi: 10.11622/smedj.2018152. Epub 2018 Nov 29.
The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome.
Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses.
The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively.
The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.
本研究旨在探讨种族、性别和质子泵抑制剂(PPI)奥美拉唑对人类肠道微生物组的影响。PPI 常用于治疗与酸相关的疾病。我们假设 PPI 治疗可能会扰乱微生物群落并改变肠道微生物组。
本研究纳入了 12 名中国裔、12 名马来裔和 10 名印度裔健康受试者,年龄在 21-37 岁之间。他们提供了基线粪便样本(第 1 天),然后接受了为期 7 天的奥美拉唑治疗剂量(每天 20 毫克)。在第 7 天和第 14 天(停止奥美拉唑一周后)再次采集粪便样本。从粪便样本中提取微生物 DNA,然后进行聚合酶链反应、文库构建、Illumina MiSeq 测序 16S rRNA,并进行统计和生物信息学分析。
研究结果显示,奥美拉唑摄入后第 7 天物种丰富度增加(p = 0.018),第 14 天恢复到基线水平。第 7 天,前庭链球菌(p = 0.0001)和差异韦荣球菌(p = 0.0001)的相对丰度显著增加,第 14 天减少。普雷沃氏菌属、粪拟杆菌和拟杆菌 denticanum 分别是中国人、马来人和印度人的特征菌。乳杆菌科和黄杆菌属 xylanisolvens 分别是男性和女性受试者的特征分类群。
本研究表明奥美拉唑治疗后肠道微生物组发生了改变。这可能解释了与奥美拉唑治疗相关的艰难梭菌感染风险增加的潜在病理机制。