A condition known as diversion colitis frequently develops in segments of the colorectum after surgical diversion of the fecal stream; it persists indefinitely unless the excluded segment is reanastomosed. The disease is characterized by bleeding from inflamed colonic mucosa that mimics the bleeding of idiopathic inflammatory bowel disease, and it may culminate in stricture formation. We hypothesized that this condition is caused by the absence of luminal short-chain fatty acids, the preferred metabolic substrates of colonic epithelium. We studied four patients with diversion colitis, none of whom had evidence of Crohn's, idiopathic ulcerative, or infectious colitis. The excluded segment of the rectosigmoid contained negligible concentrations of short-chain fatty acids. When D-glucose was instilled, it did not undergo appreciable anaerobic fermentation. Instillation of a solution containing short-chain fatty acids twice daily resulted in the disappearance of symptoms and the inflammatory changes observed at endoscopy, over a period of four to six weeks. Remission has been maintained for up to 14 months (in one patient) by instillation daily to twice weekly. Administering enemas containing isotonic saline, or omitting treatment for periods of two to four weeks during the regimen, by contrast, did not produce any improvement or rapid relapse of the colitis. Histologic observation revealed a distinctive type of mucosal inflammation that resolved more slowly and less completely than the gross appearance of the inflamed mucosa. From these preliminary studies we infer that diversion colitis may represent an inflammatory state resulting from a nutritional deficiency in the lumen of the colonic epithelium, which is effectively treated by local application of short-chain fatty acids, the missing nutrients.

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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-

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