Antioxidative and immunomodulatory effects of tributyrin supplementation on experimental colitis

Abstract

Tributyrin (TBT) is a TAG composed of three butyric acids that has beneficial effects on ulcerative colitis due to its trophic, anti-inflammatory, pro-apoptotic and anti-carcinogenic properties. The goal of the present study was to evaluate the efficacy and mechanisms of action of TBT supplementation in the prevention of mucosal damage in experimental colitis. Mice received either a control diet or a TBT-supplemented diet for 15 d. Colitis was induced by dextran sodium sulphate administration during the last 7 d. Mucosal damage and the activation of immune cells and cytokines were determined by histological score, flow cytometry and ELISA. Leucocyte rolling and adhesion were assessed by intravital microscopy. Oxidative stress was determined by monitoring hydroperoxide concentration and evaluating superoxide dismutase (SOD) and catalase activities. Intestinal permeability was analysed using diethylenetriaminepentaacetate acid ( 99mTc DTPA). Compared with the colitis group, the animals in the colitis þ TBT group had reduced mucosal damage and neutrophil and eosinophil mucosal infiltration, which were associated with a higher percentage of regulatory T cells (Treg) and higher levels of transforming growth factor b and IL-10 in the lamina propria. The level of in vivo leucocyte adhesion in the colon microvasculature was reduced after TBT supplementation. A lower level of hydroperoxide and higher levels of SOD and catalase activities were associated with TBT supplementation. TBT-supplemented mice showed reduced intestinal permeability to the levels intermediate between the control and colitis groups. In conclusion, the present results show that TBT has positive effects on colonic restructuring in experimental colitis. Additionally, TBT supplementation changes the immune response by controlling inflammation and regulating the expression of anti-inflammatory cytokines and Treg.

Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor–Dependent Repression of Claudin-2

“…These results further suggest that administration of butyrate (e.g. tributyrin) and/or promoting butyrate-producing bacteria may be of therapeutic benefit (55). …”

Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function

“…The protection afforded by fiber and resistant starch in experimental colitis are thought to be dependent on SCFA production (Ito et al, 2009; Morita et al, 2004; Videla et al, 2001), and administration of exogenous butyrate promotes resistance to experimental colitis (Cresci et al, 2013; Leonel et al, 2013). Studies investigating dysbiosis in inflammatory bowel disease identified reduced abundance of butyrate-producing organisms (e.g., certain Roseburia and Faecalibacterium genera) and lower concentrations of butyrate associated with disease (Machiels et al, 2013; Eeckhaut et al, 2013; Sokol et al, 2009).…”

Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids

“…Microbial dysbiosis observed in many metabolic diseases can alter SCFA production and crossfeeding rates, leading to changes in colonic SCFA concentrations and ratios. Tributyrin, a butyrate produg, has been shown to reduce mucosal damage and intestinal permeability in experimental colitis (29). In addition, tributyrin has been shown to attenuate obesity-associated inflammation and insulin resistance (52).…”