Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

Abstract

OBJECTIVES:To study the effect of short‐chain fatty‐acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis.INTRODUCTION:Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short‐chain fatty‐acid deficiency in the colon lumen.METHODS:Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short‐chain fatty‐acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post‐operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores.RESULTS:There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022).CONCLUSION:Therapeutic use of short‐chain fatty‐acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy.

Relationship between the Severity of Diversion Colitis and the Composition of Colonic Bacteria: A Prospective Study

“…Thus, SCFA enemas have been used to treat diversion colitis 8-11. Other studies have suggested that oxidative DNA damage and a mutation of p53 can lead to diversion colitis 12-14.…”

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 .…”

“…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 .…”

“…Studies have shown that fecal stream restoration reverts the disease symptoms in most cases, making it the most effective therapy for the prevention of DC 13 .However, fecal traffic recovery is not always possible, which promotes the evaluation of other therapeutic strategies 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 .…”

Pathobiology and Potential Therapeutic Value of Intestinal Short-Chain Fatty Acids in Gut Inflammation and Obesity

“…Several mechanisms for the development of diversion colitis have been proposed, including a nutritional deficiency of SCFA in the colonic lumen [101, 102]. Studies in Wistar rats suggest that the use of SCFA enemas may improve symptoms [102, 103]. Harig et al [101] successfully treated patients with diversion colitis using SCFA enemas.…”