FFA2 activation combined with ulcerogenic COX inhibition induces duodenal mucosal injury via the 5-HT pathway in rats

Luminal free fatty acid receptor 2 agonists stimulate enterochromaffin cells and release serotonin, which enhances mucosal defenses in rat duodenum. However, overdriving serotonin release with high luminal concentrations of free fatty acid 2 ligands such as short-chain fatty acids injures the mucosa by decreasing mucosal blood flow. These results are likely implicated in serotonin-related dyspeptic symptom generation because of small intestinal bacterial overgrowth, which is hypothesized to generate excess short-chain fatty acids in the foregut, overdriving serotonin release from enterochromaffin cells.