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Laboratory Investigation (2013) 93, 834843 & 2013 USCAP, Inc All rights reserved 0023-6837/13
Butyric acid attenuates intestinal inflammation in murine DSS-induced colitis model via milk fat globule-EGF factor 8
Tsuyoshi Mishiro1, Ryusaku Kusunoki1, Aya Otani1, Md Mesbah Uddin Ansary1, Miki Tongu2, Nanae Harashima3, Takaya Yamada2, Shuichi Sato4, Yuji Amano4, Kazuhito Itoh5, Shunji Ishihara1 and Yoshikazu Kinoshita1
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/) and MFG-E8 / mice. Although the colonic bacterial compositions in wild-type (WT) and MFG-E8 / 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 anti-inflammatory effects partly via MFG-E8 on DSS-induced murine experimental colitis.
Laboratory Investigation (2013) 93, 834843; doi:http://dx.doi.org/10.1038/labinvest.2013.70
Web End =10.1038/labinvest.2013.70 ; published online 10 June 2013
KEYWORDS: apoptosis; butyric acid; intestinal inflammation; milk fat globule-epidermal growth factor 8; 16S rRNA sequence
The cells of hundreds of different kinds of microbes far exceeding the total number of cells that comprise human tissues exist in the gastrointestinal tract, where they shape enteric microflora (gut microbiota) and build an original metabolism system. It...