Butyrate modulates oxidative stress in the colonic mucosa of healthy humans

      Summary

      Background & Aims

      Butyrate, a short-chain fatty acid produced by colonic microbial fermentation of undigested carbohydrates, has been implicated in the maintenance of colonic health. This study evaluates whether butyrate plays a role in oxidative stress in the healthy colonic mucosa.

      Methods

      A randomized, double blind, cross-over study with 16 healthy volunteers was performed. Treatments consisted of daily rectal administration of a 60 ml enema containing 100 mM sodium butyrate or saline for 2 weeks. After each treatment, a blood sample was taken and mucosal biopsies were obtained from the sigmoid colon. In biopsies, the trolox equivalent antioxidant capacity, activity of glutathione-S-transferase, concentration of uric acid, glutathione (GSH), glutathione disulfide and malondialdehyde, and expression of genes involved in GSH and uric acid metabolism was determined. Secondary outcome parameters were CRP, calprotectin and intestinal fatty acid binding protein in plasma and histological inflammatory scores.

      Results

      Butyrate treatment resulted in significantly higher GSH (p < 0.05) and lower uric acid (p < 0.01) concentrations compared to placebo. Changes in GSH and uric acid were accompanied by increased and decreased expression, respectively, of their rate limiting enzymes determined by RT–PCR. No significant differences were found in other parameters.

      Conclusions

      This study demonstrated that butyrate is able to beneficially affect oxidative stress in the healthy human colon.

      Keywords

      Non-standard abbreviations:

      ROS (reactive oxygen species), tGSH (total glutathione), GSH (reduced glutathione), GSSG (glutathione disulfide), TEAC (trolox equivalent antioxidant capacity), GST (glutathione-S-transferase), MDA (malondialdehyde), CANX (calnexin), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), 18SrRNA (18S ribosomal RNA), GPX (glutathione peroxidase), GR (glutathione reductase), GS (glutathione synthetase), GCLC (glutamate–cysteine ligase, catalytic subunit), GCLM (glutamate–cysteine ligase, modifier subunit), XDH (xanthine dehydrogenase)
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