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An Assessment of Human Gastric Fluid Composition as a Function of PPI Usage

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An Assessment of Human Gastric Fluid Composition as a Function of PPI Usage

Emily Foltz et al. Physiol Rep.

Abstract

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 × 10(6) -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.

Keywords: Bile; gastric fluid; gastricsin; proton pump inhibitors; trypsin.

Figures

Figure 1.
Figure 1.
(A) Concentrations of pepsin (n = 42) and gastricsin (n = 36) in human gastric fluid. Concentrations are expressed in arbitrary units and were determined as described in the Methods. The data are normalized such that the mean concentration of each enzyme is 1.0. (ND = Not Detectable) (B) Concentration of Pepsin graphed against concentration of gastricsin in gastric fluid (n = 35). The single coordinate (ND, ND) corresponds to 11 data points. Samples with one or more concentrations that were not detected are not included in the regression statistics. The means and standard errors are indicated by the bars.
Figure 2.
Figure 2.
(A) Bile concentration graphed against trypsin concentration (n = 64). Bile concentration is expressed in micromoles per liter and was determined by an enzymatic method as described in the Methods. Trypsin concentration is expressed in micrograms per liter and was determined by ELISA as described in the Methods. (B) Trypsin concentrations graphed against pepsin concentrations (n = 41). Samples with a pepsin concentration that was not detected are not included in the regression statistics.
Figure 3.
Figure 3.
Linear regression between log Trypsin concentration versus pH. Open circles and the dashed line represent samples from patients not on PPIs (n = 39) and corresponding best fit linear regression line. Closed circles and the solid line represent samples from patients on PPIs (n = 24) and the best fit linear regression line for those data.
Figure 4.
Figure 4.
(A) pH of gastric fluid versus PPI usage (No PPI, n = 10; PPI, n = 11). (B) Relative viscosity of gastric fluid versus PPI usage (No PPI, n = 39; PPI, n = 25). Relative viscosity was calculated using a sucrose standard curve. The means and standard errors are indicated by the bars.
Figure 5.
Figure 5.
(A) Representative flow cytometry data for a gastric fluid sample. Data were collected as described above and size gates were used to separate live bacteria (top right section indicated by the lines) from bacterial cell fragments (top left section indicated by the lines). (B) Counts of live and dead bacteria versus PPI usage (No PPI, n = 16; PPI, n = 10). The count for a given parameter on each sample is represented by a circle on the graph, closed circle representing live bacteria and open circle representing dead bacteria (particles). Total particle count is represented by an X. The means and standard errors are indicated by the bars.
Figure 6.
Figure 6.
(A) Pepsin concentration in gastric fluid as a function of PPI usage (No PPI, n = 8; PPI, n = 7). (B) Gastricsin concentration in gastric fluid as a function of PPI usage (No PPI, n = 8; PPI, n = 5). (C) Trypsin concentration in gastric fluid as a function of PPI usage (No PPI, n = 25; PPI, n = 17). (D) Bile concentration in gastric fluid as a function of PPI usage (No PPI, n = 24; PPI, n = 17). Samples from patients on PPIs with a pH less than 3.0 and samples from patients not taking PPIs with a pH greater than 3.0 was excluded from the analysis (n = 21 samples excluded). The means and standard errors are indicated by the bars.

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