Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency.
The short-chain fatty acid butyrate, which is mainly produced in the lumen of the large intestine by the fermentation of dietary fibers, plays a major role in the physiology of the colonic mucosa. It is also the major energy source for the colonocyte. Numerous studies have reported that butyrate metabolism is impaired in intestinal inflamed mucosa of patients with inflammatory bowel disease (IBD). The data of butyrate oxidation in normal and inflamed colonic tissues depend on several factors, such as the methodology or the models used or the intensity of inflammation. The putative mechanisms involved in butyrate oxidation impairment may include a defect in beta oxidation, luminal compounds interfering with butyrate metabolism, changes in luminal butyrate concentrations or pH, and a defect in butyrate transport. Recent data show that butyrate deficiency results from the reduction of butyrate uptake by the inflamed mucosa through downregulation of the monocarboxylate transporter MCT1. The concomitant induction of the glucose transporter GLUT1 suggests that inflammation could induce a metabolic switch from butyrate to glucose oxidation. Butyrate transport deficiency is expected to have clinical consequences. Particularly, the reduction of the intracellular availability of butyrate in colonocytes may decrease its protective effects toward cancer in IBD patients.
Thibault
Ronan
R
UMR 1280 Physiologie des Adaptations Nutritionnelles, INRA, Université de Nantes, CHU Nantes, Nantes, France. ronan.thibault@chu-nantes.fr
Blachier
François
F
Darcy-Vrillon
Béatrice
B
de Coppet
Pierre
P
Bourreille
Arnaud
A
Segain
Jean-Pierre
JP
D000818:Animals; D001692:Biological Transport; D002087:Butyrates / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology
D002087:Butyrates