Butyric acid attenuates intestinal inflammation in murine DSS-induced colitis model via milk fat globule-EGF factor 8

Abstract

Butyric acid, a short-chain fatty acid and one of the main metabolites of intestinal microbial fermentation of dietary fiber, has been shown to have an important role in maintaining the integrity of the intestinal mucosa, while it also has been shown to exert potent anti-inflammatory effects both in vitro and in vivo. However, the precise mechanisms underlying those effects have not been fully identified. We exposed colonic epithelial cells to butyric acid, then extracted total RNA samples, and subsequently hybridized them to microarray chips. Among the upregulated genes, milk fat globuleepidermal growth factor 8 (MFG-E8) was elevated by approximately fivefold. We previously reported that the potential therapeutic benefits of MFG-E8 in intestinal tissue injury were dependent not only on enhanced clearance of apoptotic cells but also required diverse cellular events for maintaining epithelial integrity. The influence of butyric acid on cell function is often attributed to its inhibition of histone deacetylases (HDACs). We found that acetylation on histone 3 lysine 9 (acetyl-H3K9) around the MFG-E8 promoter was significantly increased with butyric acid exposure. Experimental colitis was induced by administration of dextran sodium sulfate (DSS) in C57BL/6N (MFG-E8 þ / þ ) and MFG-E8 À / À mice. Although the colonic bacterial compositions in wild-type (WT) and MFG-E8 À / À mice were not significantly different, intrarectal administration of butyric acid during an acute phase of colitis attenuated intestinal inflammatory parameters and inhibited body weight loss in the WT mice. Our novel findings suggest that butyric acid has significant antiinflammatory effects partly via MFG-E8 on DSS-induced murine experimental colitis.

The definition of neutrophil extracellular traps and the concentration of short-chain fatty acids in salmonella-induced inflammation of the intestine against the background of vancomycin and Bacteroides fragilis

“…In the studies on different experimental models (dextran sulfate-sodium colitis [46], T-cell-dependent colitis [47,48], thioglycollate-induced peritonitis [49], acute renal failure [50]), the researchers determined that activation of SCFA reduces the restructuring of the neutrophil cytoskeleton and the intensity of inflammatory responses. This fact is confirmed by the investigation of Mishiro (2013) that was conducted on mouse models with dextran sulfate-sodium colitis and rectal administration of butyrate in which the weakening of the rearrangement of the cytoskeleton of neutrophils and reduction in inflammation were also observed [51]. The results obtained by Kim (2013), likewise show a reduction in inflammatory responses due to the interaction of neutrophils with SCFA and epithelial cells of the intestine (GPR41), when C. rodentium mice are infected with the subsequent introduction of acetate.…”

Butyric acid in irritable bowel syndrome

“…The ability of butyrate to decrease concentrations of pro-inflammatory cytokines such as interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α) has been documented [26]. In mice, the intrarectal administration of butyric acid during an acute phase of experimental colitis attenuated intestinal inflammatory parameters [27]. Some anti-inflammatory effects of butyrate in the treatment of ulcerative colitis and radiation proctitis were also observed [28, 29].…”

Differential Responses of Cecal Microbiota to Fishmeal, Eimeria and Clostridium perfringens in a Necrotic Enteritis Challenge Model in Chickens

“…Interestingly SCFAs, especially butyrate, are also reduced in human colitis patients [9], [10]. Butyrate aids mucosal immunity and differentiation of colonic regulatory T cells [11] and it has the ability to attenuate symptoms of colitis [12].…”