Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function
Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function
复制标题
DOI：
10.1152/ajpgi.00268.2014
复制
发表时间：
2014-11-15
影响因子：
4.5
通讯作者：
Gillevet, Patrick M.
中科院分区：
文献类型：
--
作者：
Bajaj, Jasmohan S.;Cox, I. Jane;Gillevet, Patrick M.
质子泵抑制剂（PPI）与肝硬化的感染性并发症有关，但其对远端肠道微生物群组成和功能的影响尚不清楚。我们的目的是评估奥美拉唑治疗后肝硬化患者和健康对照者粪便微生物群组成和功能的变化。15名代偿性腹泻患者和15名年龄匹配的对照者均接受了血清胃泌素测量、粪便微生物群分析（多标记焦磷酸测序）和尿代谢分析（NMR光谱），以评估在恒定饮食条件下接受40 mg/天奥美拉唑14天疗程之前/之后的微生物彗星试验。采用系统生物学技术比较两组PPI治疗前和治疗后的结果。在研究期间，在饮食或MELD（终末期肝病模型）评分没有变化的情况下，依从性>95%。肝硬化患者PPI治疗后血清胃泌素浓度显著升高（治疗前38.3 +/- 35.8 vs. 115.6 +/- 79.3 pg/ml，P < 0.0001），对照组患者PPI治疗后血清胃泌素浓度显著升高（治疗前29.9 +/- 14.5 vs. 116.0 +/- 74.0 pg/ml，P = 0.001）。在对照组和奥美拉唑后肝硬化组中均观察到显著的微生物群变化（QIIME P < 0.0001）。相对链球菌科丰度，通常丰富的唾液中，显着增加对照组（1对5%）和肝硬化（0对9%），并与血清胃泌素水平（r = 0.4，P = 0.005）。我们发现，肝硬化患者的马尿酸盐在术前和术后均显著低于对照组，而两组患者的乳酸盐在术后均高于术前奥美拉唑组，而二甲胺（DMA）仅在肝硬化患者中降低。在相关网络分析，显着的变化，细菌与代谢产物（马尿酸/DMA/乳酸）的联系，发现postmortality，与前PPI肝硬化患者。总之，奥美拉唑与代偿性肝硬化患者远端肠道微生物群转移和功能变化相关，这可能为细菌过度生长奠定基础。
Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions. Results before (pre) and after PPI were compared in both groups, compared with baseline by systems biology techniques. Adherence was >95% without changes in diet or MELD (model for end-stage liver disease) score during the study. Serum gastrin concentrations significantly increased after PPI in cirrhosis (pre 38.3 +/- 35.8 vs. 115.6 +/- 79.3 pg/ml P < 0.0001) and controls (pre 29.9 +/- 14.5 vs. 116.0 +/- 74.0 pg/ml, P = 0.001). A significant microbiota change was seen in both controls and cirrhosis after omeprazole (QIIME P < 0.0001). Relative Streptococcaceae abundance, normally abundant in saliva, significantly increased postomeprazole in controls (1 vs. 5%) and cirrhosis (0 vs. 9%) and was correlated with serum gastrin levels (r = 0.4, P = 0.005). We found significantly reduced hippurate in cirrhosis vs. controls both pre- and postomeprazole and increased lactate in both groups post vs. preomeprazole, whereas dimethylamine (DMA) decreased in cirrhosis only. On correlation network analysis, significant changes in linkages of bacteria with metabolites (hippurate/DMA/lactate) were found postomeprazole, compared with pre-PPI in cirrhosis patients. In conclusion, omeprazole is associated with a microbiota shift and functional change in the distal gut in patients with compensated cirrhosis that could set the stage for bacterial overgrowth.