Effects of Short-Chain Fatty Acids on the Inflamed Colonic Mucosa

Abstract

Selected inflammatory conditions of the distal alimentary tract may respond to topical SCFA treatment. The rationale for using SCFA enemas is based on Roediger's (1980) observation that butyrate is the preferred fuel of colonocytes and that SCFA deficiency could lead, in the short term, to mucosal hypoplasia and, in the long term, to colitis. The absence of luminal nutrients is especially evident in the excluded rectum after complete diversion of the faecal stream. Harig et al. (1989) were the first to treat successfully diversion colitis with SCFA irrigation (acetate 60 mM, propionate 30 mM, n-butyrate 40 mM). However, subsequent studies could not reproduce the initial positive data. In distal ulcerative colitis an impaired mucosal oxidation of SCFAs has been described despite their luminal abundance. Pilot studies using either the SCFA mixture or butyrate monotherapy have yielded promising results. However, extended confirmatory studies with a larger sample size have not yet been performed. Preliminary data are also available for the use of SCFA in pouchitis and radiation proctitis. In summary, SCFA topical therapy seems to be a promising option in distinct forms of inflammatory bowel disease; however, the routine use of SCFAs cannot be recommended until their efficacy has been confirmed in larger trials.

Evaluation of topical n-acetylcysteine in diversion colitis

“…The application of SCFAs in the excluded colon was experimentally demonstrated to improve the inflammatory process, while the interrupted application promoted the disease dissemination 10 . The deficient supply of SCFAs as a factor that triggers DC was confirmed with the results of clinical and experimental studies showing that the restoration of fecal stream or the application of butyrate-rich solutions, the main subtype of SCFAs metabolized by colonocytes, reverted the clinical symptoms and the characteristic endoscopic and histological alterations of the disease [11][12][13][14][15][16][17][18][19] . However, despite these evidences, the molecular mechanisms through which the deficient supply of SCFAs determines the tissue inflammation, have not been fully explained 20 .…”

“…As the pathogenesis of DC is related to deficient supply of SCFAs, the most obvious strategy is to apply enemas with SCFAs in the segment without fecal stream 18,19,33,34 . A series of studies confirmed that the irrigation of segments without fecal stream with SCFAs-rich solutions, particularly butyrate, can revert endoscopic and histological alterations related to the disease and reduce the levels of tissue oxidative stress [9][10][11][12][13]15,17,18,33,34 . The main action of SCFAs in the segment without fecal stream would be to restore homeostasis in the reactions that promote energy production by the cells, preventing the excessive formation of OFRs and, consequently, the tissue oxidative stress 34 .…”

“…DC is a chronic inflammatory disease developed in 100% of the patients 36 months after the intestinal stream interruption 5,6,[9][10][11][12][13][14][15][16][17][18][19][20] . Recent studies have demonstrated that the increased OFRs production by epithelial cells with deficient SCFAs supply and the recognized deficiency of colonic mucosa in antioxidant enzymatic systems, which makes the intestinal epithelium particularly vulnerable to oxidative stress, are mechanisms related to the pathogenesis of DC 20,27 .…”

Late rectal complications after prostate brachytherapy for localized prostate cancer

“…53 Several studies of SCFA enemas to promote healing of postradiation mucosal lesions have yielded conflicting results. Initial studies indicated a decrease in rectal bleeding and endoscopic improvements with SCFA use, [54][55][56] but those findings were not reproduced in a subsequent prospective, randomized, double-blind study.…”

The importance of oxygen free radicals in the etiopathogenesis of diversion colitis in rats

“…Various theories regarding the pathogenesis of DC have been proposed but most of authors believe that DC arises due to the absence of short chain fattyacids (SCFAs) in the intestinal lumen due to the diversion of the fecal stream 2,3,4,5 . However, the molecular mechanism by which SCFAs deficiency causes epithelial aggression has been not been studied in experimental models of DC.…”