Butyrate in ulcerative colitis and pouchitis: friend or foe?

It is widely known that the short chain fatty acid (SFA) butyrate, generated mainly through fermentation of dietary fibre by anaerobic bacteria, has beneficial effects on health. Less widely known is that butyrate, at the concentration (c20 mM) typically found in the healthy colonic lumen, is toxic to colon epithelial cells. It is probably the presence of the continuous adherent mucus layer in the healthy colon that ensures that butyrate concentrations in contact with the epithelium fall below the levels (c > 3 mM) that are consistently toxic in in vitro or ex vivo studies. In active ulcerative colitis, the adherent mucus layer is commonly weakened or absent. In this situation, it is likely that the luminal butyrate concentration will be toxic to the epithelium. It follows that butyrate at concentrations typically present in the colon lumen is probably beneficial when colitis is in remission but harmful when colitis has relapsed. This may explain the largely negative results of butyrate therapy in ulcerative colitis and could also account for the recently reported benefit from total enteral nutrition. It also suggests that butyrate should be regarded as a target for therapy in active ulcerative colitis rather than a solution.