Gastroduodenal mucosal defense mechanisms

Abstract

Purpose of Review To highlight recent developments in the field of gastroduodenal mucosal defense with emphasis on lumen-gut interactions. Recent Findings There has been a growing interest in the physiological functions of luminal chemosensors present from tongue to colon that detect organic molecules in the luminal content associated with nutrient ingestion, usually associated with specialized cells, in particular the enteroendocrine cells. These receptors transduce the release of peptide hormones, in particular proglucagon-derived products such as the glucagon-like-peptides (GLPs), which have profound effects on gut function and on metabolism. Luminal chemosensors transduce GLP release in response to changes in the cellular environment, as part of the mechanism of nutrient chemosensing. GLP-2 has important trophic effects on the intestinal mucosa, including increasing the proliferation rate of stem cells and reducing transmucosal permeability to ions and small molecules, in addition to increasing the rate of duodenal bicarbonate secretion. GLP-1, although traditionally considered an incretin that enhances the effect of insulin on peripheral tissues, also has trophic effects on the intestinal epithelium. Summary A better understanding of the mechanisms that mediate GLP release can further illuminate the importance of nutrient chemosensing as an important component of the mechanism that mediates the trophic effects of luminal nutrients. GLP-1 and -2 are already in clinical use for the treatment of diabetes and intestinal failure. Improved understanding of the control of their release and their end-organ effects will identify new clinical indications and interventions that enhance their release.

Gene expression and morphological changes in the intestinal mucosa associated with increased permeability induced by short‐term fasting in chickens

“…Heat‐shock protein‐70 expression was not altered in the jejunum and ileum after fasting, similar to another study in which fasting did not change expression of this gene in the liver (Delezie, Swennen, Buyse, & Decuypere, ). Glucagon‐like peptide‐2 produced in the intestine has been shown to reduce intestinal inflammation (Burrin, Stoll, & Guan, ; Richards & McMurtry, ), permeability (Dong et al., ) and bacterial translocation (Burrin et al., ; Said, Kaji, & Kaunitz, ). Glucagon‐like peptide‐2 results are comparable to another study in chickens, in which fasting did not alter GLP‐2 expression in the proventriculus and the duodenum (Richards & McMurtry, ).…”

Eicosanoids in the gastrointestinal tract

“…Duodenal bicarbonate secretion is particularly important for protection of the tissue from high concentrations of gastric acid, and its mechanisms have been well characterized. PGE 2 stimulates duodenal bicarbonate secretion in rats via activation of EP 3 and EP 4 receptors (Takeuchi et al ., ; Said et al ., ).…”

Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways

“…The duodenal mucosa, because of its strategic location between the stomach and the rest of the small intestine, senses luminal nutrients, affects appetite, and regulates duodenal anion secretion, particularly HCO 3 2 secretion, which in turn is important for nutrient absorption and mucosal protection from gastric acid (Kaji et al, 2013). We have been investigating the contributions of enteroendocrine cells (EECs) and afferent sensory nerves that link the duodenal mucosa with mucosal defense mechanisms (Akiba and Kaunitz, 2011;Said et al, 2015). As part of this quest, we hypothesized that xenin, a homolog of amphibian xenopsin and mammalian neurotensin (NT) (Feurle et al, 1992), which is specifically generated in the duodenal mucosa, directly affects duodenal anion secretion.…”