Abstract
BackgroundFermentation of dietary fiber in the colon results in the production of short chain fatty acids (mainly propionate, butyrate and acetate). Butyrate modulates a wide range of processes, but its mechanism of action is mostly unknown. This study aimed to determine the effects of butyrate on the transcriptional regulation of human colonic mucosa in vivo.Methodology/Principal FindingsFive hundred genes were found to be differentially expressed after a two week daily butyrate administration with enemas. Pathway analysis showed that the butyrate intervention mainly resulted in an increased transcriptional regulation of the pathways representing fatty acid oxidation, electron transport chain and oxidative stress. In addition, several genes associated with epithelial integrity and apoptosis, were found to be differentially expressed after the butyrate intervention.Conclusions/SignificanceColonic administration of butyrate in concentrations that can be achieved by consumption of a high-fiber diet enhances the maintenance of colonic homeostasis in healthy subjects, by regulating fatty acid metabolism, electron transport and oxidative stress pathways on the transcriptional level and provide for the first time, detailed molecular insight in the transcriptional response of gut mucosa to butyrate.
Highlights
Short-chain fatty acids (SCFAs) are derived from the microbial fermentation of undigested dietary fibers in the colon
Local administration of butyrate in the distal colon resulted in an increased transcription of genes, which were mainly associated with energy metabolism, fatty acid metabolism and oxidative stress
We showed for the first time that these processes are significantly regulated on the transcriptional level by intraluminal butyrate in healthy humans
Summary
Short-chain fatty acids (SCFAs) are derived from the microbial fermentation of undigested dietary fibers in the colon. Depletion of carbohydrate sources in the distal colon leads to a switch from saccharolytic to proteolytic fermentation, which is less favorable due to the formation of potentially toxic products. Both these toxic products and the lower availability of SCFAs in the distal colon are hypothesized to be involved in the pathogenesis of gastro-intestinal disorders such as ulcerative colitis (UC) and cancer [1,2,3]. Among the different SCFAs, butyrate is known to modulate numerous processes. Fermentation of dietary fiber in the colon results in the production of short chain fatty acids (mainly propionate, butyrate and acetate). This study aimed to determine the effects of butyrate on the transcriptional regulation of human colonic mucosa in vivo
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