Abstract. Background-Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. Aims-To assess the efficacy of topical SCFA treatment in ulcerative colitis. Patients and Methods-103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial. Results-Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p=0 14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (<6 months, n=42), more responded to SCFA than to placebo (48% v 18%, p=003). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p=0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p<0.02) in their clinical and histological activity scores. Conclusions-Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit. (Gut 1997; 40: 485-491) Keywords: short chain fatty acids, distal ulcerative colitis.Treatment of distal ulcerative colitis consists mainly of topical or oral 5-aminosalicylic acid (5-ASA) compounds or corticosteroids, or both. These compounds alter the inflammatory response by decreasing oxygen free radical activity and proinflammatory cytokine release, and by modifying the lipo-and cyclooxygenase pathways of arachidonic acid metabolism.' They are relatively expensive, not uniformly effective, are not free of undesired systemic effects even in their new formula-

Colon cells from patients with ulcerative colitis utilize short-chain fatty acids inefficiently and may be exposed to decreased concentrations of these compounds. To test whether irrigation of the inflamed mucosa with short-chain fatty acids is useful, we conducted a six-week preliminary trial in 12 patients with distal colitis. Each patient used twice daily rectal irrigations with 100 ml of a solution containing acetate (80 mM), propionate (30 mM), and butyrate (40 mM). Two patients stopped at three weeks, one because of no improvement and the other because of complete resolution of symptoms. Of the 10 who completed the trial, nine were judged to be at least much improved and showed a change in a mean disease activity index score from 7.9 +/- 0.3 (SE) to 1.8 +/- 0.6 (SE) (P less than or equal to 0.002) and in a mucosal histology score from 7.7 +/- 0.7 (SE) to 2.6 +/- 0.7 (SE) (P less than or equal to 0.002). Thus, ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates.