An assessment of human gastric fluid composition as a function of PPI usage.
An assessment of human gastric fluid composition as a function of PPI usage.
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DOI：
10.14814/phy2.12269
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发表时间：
2015-01-01
影响因子：
2.5
通讯作者：
Lin SS
中科院分区：
文献类型：
--
作者：
Foltz E;Azad S;Everett ML;Holzknecht ZE;Sanders NL;Thompson JW;Dubois LG;Parker W;Keshavjee S;Palmer SM;Davis RD;Lin SS
慢性胃食管反流病（GERD）影响高达40%的人群，其标准治疗是使用质子泵抑制剂（PPI）等药物来阻断胃酸的产生。尽管PPI广泛使用，但其对胃液的影响仍不明确。在本研究中，采集了未（n = 40）或正在（n = 25）积极服用PPI的心脏手术患者的胃液。利用各种酶和免疫测定法以及质谱法分析胃液中胆汁、胃蛋白酶、胰蛋白酶和胃蛋白酶的浓度。通过质谱法进行的蛋白质组学分析表明，胰蛋白酶在低pH值下的降解可能至少部分地解释了观察结果，即服用PPI的患者更有可能在其胃液中具有高浓度的胰蛋白酶。一般而言，评价的所有分析物的浓度在几个数量级上变化，最小范围为2000倍（胃泌素），最大范围为1 × 106倍（胰蛋白酶）。此外，样品中各种分析物的浓度彼此之间的相关性很差。例如，胰蛋白酶和胆汁浓度显示出显著（P < 0.0001）但不强的相关性（r = 0.54）。最后，通过流式细胞术对细菌浓度的直接评估显示，PPI不会导致胃液中微生物负荷的显著增加。这些结果进一步阐明了PPI使用对胃生理学的深远影响。为了进一步描述PPI使用对胃生理学的深远影响，从接受心脏手术的患者中收集了胃液，这些患者未（n = 40）或正在（n = 25）积极服用PPI。通过质谱法进行的蛋白质组学分析表明，胰蛋白酶在低pH值下的降解可能至少部分地解释了观察结果，即服用PPI的患者更有可能在其胃液中具有高浓度的胰蛋白酶。通过流式细胞术对细菌浓度的直接评估显示，PPI不会导致胃液中微生物负荷的显著增加，这与先前使用培养依赖性方法获得的结果相反。
The standard of care for chronic gastro‐esophageal reflux disease (GERD), which affects up to 40% of the population, is the use of drugs such as proton pump inhibitors (PPIs) that block the production of stomach acid. Despite widespread use, the effects of PPIs on gastric fluid remain poorly characterized. In this study, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Various enzymatic and immunoassays as well as mass spectrometry were utilized to analyze the concentrations of bile, gastricsin, trypsin, and pepsin in the gastric fluid. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. In general, the concentrations of all analytes evaluated varied over several orders of magnitude, covering a minimum of a 2000‐fold range (gastricsin) and a maximum of a 1 × 106 –fold range (trypsin). Furthermore, the concentrations of various analytes were poorly correlated with one another in the samples. For example, trypsin and bile concentrations showed a significant (P < 0.0001) but not strong correlation (r = 0.54). Finally, direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid. These results further delineate the profound effects that PPI usage has on the physiology of the stomach. Further delineating the profound effects that PPI usage has on the physiology of the stomach, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. Direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid, contrary with results previously obtained using culture‐dependent methods.