Short-chain fatty acids augment rat duodenal mucosal barrier function
(English)Manuscript (preprint) (Other academic)
In humans, short-chain fatty acids (SCFAs) are produced by bacterial fermentation in the large intestine, particularly from diets containing fiber and carbohydrates. Additionally, the small intestinal epithelium is exposed to high concentrations of SCFAs derived mainly from oral bacteria or food supplementation. SCFAs and other nutrients play significant roles in the neurohumoral regulation of gastrointestinal functions. However, the role of SCFAs in the regulation of proximal small intestinal mucosal barrier function and motility has not been fully described. The aim of the present study was to study the effects of the two SCFAs acetate and propionate on the regulation of duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30-mm segment of proximal duodenum with an intact blood supply was perfused in situ. The effects on duodenal bicarbonate secretion, blood-to-lumen clearance of 51Cr-EDTA, motility and transepithelial net fluid flux were investigated.
Perfusing the duodenal segment with acetate or propionate significantly decreased the mucosal paracellular permeability and transepithelial net fluid flux and significantly increased mucosal bicarbonate secretion. Acetate or propionate administered by an intravenous (i.v.) infusion decreased the mucosal paracellular permeability without any effect on the net fluid flux. However, it significantly decreased the bicarbonate secretion. Neither luminal nor i.v. administration of SCFAs changed duodenal motility (area under the curve, AUC), although the motility pattern changed from migrating motor complexes to feeding motility. The systemic administration of glucagon-like peptide-2 (GLP-2) induced increases in both bicarbonate secretion and net fluid absorption. An i.v. GLP-2 infusion during a luminal perfusion of SCFAs significantly reduced the duodenal motility.
In conclusion, SCFAs decreased the duodenal paracellular permeability and net fluid flux and increased the mucosal bicarbonate secretion in normal rats. Altered luminal chemosensing and aberrant signaling in response to SCFAs may contribute to the symptoms observed during bacterial overgrowth in the foregut or excessive supplementation of SCFAs in patients with functional dyspepsia or suppressed mucosal barrier function.
barrier function, motility, chemosensing, short chain fatty acids, GLP-2, enteroendocrine cells, functional dyspepsia
IdentifiersURN: urn:nbn:se:uu:diva-264402OAI: oai:DiVA.org:uu-264402DiVA: diva2:860218
Research funders and strategic development areas:
- Emil and Ragna Börjesson Foundation
- Uppsala University
- Ministry of Education of Malaysia
- Universiti Malaysia Sabah, Malaysia2015-10-122015-10-112015-11-10