Gastroesophageal Reflux Disease (GERD): Is There More to the Story?

Abstract

Gastroesophageal reflux disease (GERD) affects both men and women worldwide, with the most common symptom of GERD being frequent heartburn. If left untreated, more serious diseases including esophagitis and/or esophageal cancer may result. GERD has been commonly held to be the result of gastric acid refluxing into the esophagus. Recent work, however, has shown that there are acid-producing cells in the upper aerodigestive tract. In addition, acid-producing bacteria located within the upper gastrointestinal tract and oral cavity may also be a contributing factor in the onset of GERD. Proton pump inhibitors (PPIs) are commonly prescribed for treating GERD; these drugs are designed to stop the production of gastric acid by shutting down the H(+)/K(+)-ATPase enzyme located in parietal cells. PPI treatment is systemic and therefore significantly different than traditional antacids. Although a popular treatment choice, PPIs exhibit substantial interpatient variability and commonly fail to provide a complete cure to the disease. Recent studies have shown that H(+)/K(+)-ATPases are expressed in tissues outside the stomach, and the effects of PPIs in these nongastric tissues have not been fully explored. Likewise, acid-producing bacteria containing proton pumps are present in both the oral cavity and esophagus, and PPI use may also adversely affect these bacteria. The use of PPI therapy is further complicated by the two philosophical approaches to treating this disease: to treat only symptoms or to treat continuously. The latter approach frequently results in unwanted side effects which may be due to the PPIs acting on nongastric tissues or the microbes which colonize the upper aerodigestive tract.

The Effect of Proton Pump Inhibitors on the Human Microbiota

“…The H + /K + -ATPase pump is classified as a member of the P-type, or ion-motive-phosphorylating, ATPase family because the ion transport of this particular proton pump is coupled to a cycle of phosphorylation and dephosphorylation. (For a more detailed explanation of the gastric H + /K + -ATPase, and its involvement in acid production and regulation, the reader is again directed to our recent review [7].) P-type ATPases are not restricted to only gastric proton pumps in humans; a number of non-gastric H + /K + -ATPases, Na + /K + -ATPases, and Ca 2+ -ATPases are also members of the P-type family [7,20,21,29].…”

“…Consequently, GERD patients are treated with PPIs on a continuous basis, even when no symptoms are present. While the PPIs are designed to mechanistically shut off the H + /K + -ATPase proton pumps of parietal cells in the stomach, evidence has shown that other human tissues also contain cells possessing the H + /K + -ATPase enzyme [7,[20][21][22][23][24]. Furthermore, commensal acid-producing bacteria have been found in the stomach, upper aerodigestive tract, and oral cavity [25,26].…”

“…1) are designed as weak bases which can react with secreted acid in the parietal cells, resulting in a thiophilic form of the drug which can then bind to the cysteine residues of the proton pump (H + /K + -ATPase), effectively blocking acid transport [5,6]. (For a more thorough discussion of gastric acid secretion and other drugs used to treat GERD, please see our recent review [7]. )…”

Knowledge and Usage Patterns of Folic Acid amongst Physician Assistant Students at the University of Texas Medical Branch at Galveston.

“…In the stomach, gastric acid is produced by the parietal cells located in the lining of the stomach through the action of H + /K + -ATPase, known as the gastric proton pump [10]. Regulation of stomach pH is a complex process that includes stimulation by gastrin, histamine, and acetylcholine ( Figure 1) [10][11][12].…”

“…Regulation of stomach pH is a complex process that includes stimulation by gastrin, histamine, and acetylcholine ( Figure 1) [10][11][12]. Secretion of gastric acid is evoked by a number of physiologic stimuli, including the presence of food in the stomach or intestines, or merely the taste, smell, or thought of food [10][11][12]. Proton pump inhibitors block the last stage of acid production and secretion of acid into the lumen of the stomach by inhibiting the action of the gastric proton pump, causing a rise in the gastric pH ( Figure 1) [12].…”