Butyrate utilization by the colonic mucosa in inflammatory bowel diseases

Abstract

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.

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

“…In vivo validation of the preference of butyrate producers to reside in mucus together with better understanding of factors that drive these processes may allow to develop novel therapies. As mucosal butyrate producers release butyrate close to the epithelium, they may enhance butyrate bioavailability for the host, which may be particularly useful for IBD patients where transport of butyrate to colonocytes is impaired (Thibault et al, 2010). The mucosal environment of the M-SHIME prevents wash-out of microbes that disappeared from conventional in vitro models ( Figure 5).…”

Adaptation to High Grain Diets Proceeds Through Minimal Immune System Stimulation and Differences in Extracellular Matrix Protein Expression in A Model of Subacute Ruminal Acidosis in Non-lactating Dairy Cows

“…As a result, lipopolysaccharide (LPS) levels, derived and shed from the cell walls of such bacteria, significantly increase both in the rumen and in the systemic circulation (Motoi et al, 1993). Increases in acidity, coupled with LPS work together to damage the rumen, cause the initial local inflammatory reaction (Gozho et al, 2005) and initiate an immune-mediated cascade that will eventually lead to antigen clearance, ruminal wound healingand the reestablishment of metabolic homeostasis (Thibault et al, 2010).…”

The microbiome in inflammatory bowel disease and its modulation as a therapeutic manoeuvre

“…Butyrate, a SCFA, is derived from microbial fermentation of dietary starches. It is the major energy source for colonocytes and both butyrate and butyrate producing bacteria have been shown to be deficient in the inflamed colon (28)(29)(30) . Butyrate enemas, although not in common clinical use, have been used as a therapy in IBD, highlighting the importance of the microbiota (31) .…”