Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
Hepatol Int. 2019 Mar;13(2):234-244. doi: 10.1007/s12072-019-09932-9. Epub 2019 Feb 8.
Current knowledge suggests that proton pump inhibitors (PPIs) are associated with an increased risk of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). These conditions and PPI use are related to gut microbiota. The aim of this study is to research the changes in gut microbiota caused by PPI in patients with chronic liver disease.
From 198 Japanese patients, 31 patients in the PPI and non-PPI groups were matched using propensity score matching (PSM) based on age, sex, and Child-Turcotte-Pugh class. We investigated the gut microbial composition of stool samples using the Illumina MiSeq sequencing platform and compared them using linear discriminant analysis effect size and phylogenetic investigation of communities by reconstruction of unobserved states.
Before PSM, Child-Turcotte-Pugh score (p = 0.038), ascites (p = 0.049), encephalopathy (p = 0.023), and esophageal varices (p < 0.01) were significantly higher in the PPI group than in the non-PPI group. After PSM, six genera, consisting of Lactobacillus, Streptococcus, Selenomonas, Veillonella, Campylobacter, and Haemophilus were enriched in the PPI group. Eggerthella, Paraprevotella, Turicibacter, Dorea, Anaerotruncus, and Ruminococcus were less abundant in the PPI group. We identified five types of level 3 KEGG pathways predicted to be significantly different.
Part of microbial changes caused by PPI use was common to the changes by progression of liver cirrhosis. Increases in oral bacterial flora and decreases in autochthonous flora may produce the intestinal environment which tends to make the risk factor for HE or SBP.
目前的知识表明，质子泵抑制剂（PPIs）与肝性脑病（HE）和自发性细菌性腹膜炎（SBP）的风险增加有关。这些情况和 PPI 的使用与肠道微生物群有关。本研究旨在研究 PPI 引起的慢性肝病患者肠道微生物群的变化。
从 198 名日本患者中，通过倾向评分匹配（PSM）基于年龄、性别和 Child-Turcotte-Pugh 分级，将 31 名 PPI 和非 PPI 组患者进行匹配。我们使用 Illumina MiSeq 测序平台研究粪便样本的肠道微生物组成，并使用线性判别分析效应大小和未观察状态重建的群落系统发育分析进行比较。
在 PSM 之前，Child-Turcotte-Pugh 评分（p=0.038）、腹水（p=0.049）、脑病（p=0.023）和食管静脉曲张（p<0.01）在 PPI 组中明显高于非 PPI 组。PSM 后，PPI 组中丰度增加的有乳杆菌属、链球菌属、唾液单胞菌属、韦荣球菌属、弯曲杆菌属和嗜血杆菌属等 6 个属。PPI 组中埃格特氏菌属、副拟杆菌属、瘤胃菌属、多雷亚菌属、厌氧真杆菌属和瘤胃球菌属等 5 个属较少。我们鉴定出 5 种预测为显著不同的水平 3 KEGG 途径。
PPI 使用引起的部分微生物变化与肝硬化进展引起的变化相同。口腔细菌菌群的增加和固有菌群的减少可能产生肠道环境，使 HE 或 SBP 的风险因素更容易发生。
