Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin

Abstract

Secretion of bicarbonate into the adherent layer of mucus gel creates a pH gradient with a near-neutral pH at the epithelial surfaces in stomach and duodenum, providing the first line of mucosal protection against luminal acid. The continuous adherent mucus layer is also a barrier to luminal pepsin, thereby protecting the underlying mucosa from proteolytic digestion. In this article we review the present state of the gastroduodenal mucus bicarbonate barrier two decades after the first supporting experimental evidence appeared. The primary function of the adherent mucus gel layer is a structural one to create a stable, unstirred layer to support surface neutralization of acid and act as a protective physical barrier against luminal pepsin. Therefore, the emphasis on mucus in this review is on the form and role of the adherent mucus gel layer. The primary function of the mucosal bicarbonate secretion is to neutralize acid diffusing into the mucus gel layer and to be quantitatively sufficient to maintain a near-neutral pH at the mucus-mucosal surface interface. The emphasis on mucosal bicarbonate in this review is on the mechanisms and control of its secretion and the establishment of a surface pH gradient. Evidence suggests that under normal physiological conditions, the mucus bicarbonate barrier is sufficient for protection of the gastric mucosa against acid and pepsin and is even more so for the duodenum.

A biliary HCO3−umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes

“…29 HCO À 3 molecules are effectively trapped in the bile-acid-resistant 30 mucus gel layer of the gastric mucosa, thus establishing a local environment with a relatively high pH of $6-7 at the cell surface, whereas the bulk pH of gastric juice hovers around 1-2. [31][32][33] A similar function may be attributed to a glycocalyx of the biliary tree. However, an apical glycocalyx on cholangiocytes has never been described.…”

Helicobacter pylori moves through mucus by reducing mucin viscoelasticity

“…This feature of mucin is believed to play a crucial role in its protective function in the stomach in that by forming a gel at low pH, it forms a viscoelastic barrier protecting the lining of the stomach from damage by its own acidic secretions and other insults (28). Moreover, bicarbonate secretion maintains a gradient from pH 2 in the gastric lumen to approximately neutral pH at the epithelial surface (29,30). H. pylori, has been shown to exhibit a pH tactic response toward elevated pH (31), consistent with the established picture of a bacterium swimming through the mucus layer toward the epithelial surface and away from the highly acidic lumen.…”

The distribution and expression of CFTR restricts electrogenic anion secretion to the ileum of the brushtail possum, Trichosurus vulpecula

“…However, an important function of HCO 3 -secretion in the duodenum is protection of the duodenal epithelium from the acidic chyme delivered from the stomach into the small intestine (Allen and Flemstrom, 2005 of the eutherian duodenum are SLC26A3 and SLC26A6 (Jacob et al, 2002;Singh et al, 2008;Tuo et al, 2006;Walker et al, 2009). However, SLC26A6 contributes little to HCO 3 -secretion (Wang et al, 2005) whereas SLC26A3 is responsible for ~60% of the spontaneous HCO 3 -secretion and ~50% of the cAMP-stimulated secretion, CFTR and a small paracellular leak accounting for the remainder (Walker et al, 2009).…”

“…In addition to Cl -secretion, HCO 3 -secretion occurs in the eutherian intestinal tract, particularly in the duodenum , where HCO 3 -has an important role in the protection of the duodenal epithelium from the acidic chyme delivered from the stomach (Allen and Flemstrom, 2005). Interestingly, even in the duodenum, where the rates of HCO 3 -secretion are relatively high compared with other regions of the intestinal tract , the rate of HCO 3 -secretion is markedly less than Cl -secretion (Seidler et al, 1997).…”