EFFECTS OF BUTYRATE IN PATIENTS WITH AN ILEOANAL POUCH

Abstract

228 Pouchitis might develop in up to 46% of patients with an ileoanal pouch. The etiology of pouchitis is unknown, but it has been associated with decreased levels of short-chain fatty acids (SCFA) in the lumen of the pouch. Inulin, a dietary fiber, is fermented by intestinal bacteria into SCFA.Aim: To investigate the clinical effects of enteral inulin in patients with an ileal pouch-anal anastomosis. In addition, pouch mucosal functioning was investigated by studying epithelial gene expression.Methods: Nineteen patients with a pouch received 24 g of inulin daily for three weeks, and a placebo for three weeks, with a four weeks wash-out period in between. It was a randomized, double blind, cross-over study. Biopsies were taken after each test period. The recently proposed Pouchitis Disease Activity Index (PDAI) [Sandborn et al, Mayo Clin Proc 1994; 69:409-415] was used to investigate the potential beneficial clinical effects of enteral inulin. SCFA in stools were quantified by gas chromatography. Pouch morphology and the localization of expression of the enterocyte-specific intestinal-fatty acid binding protein (i-FABP), and goblet cells-specific mucin (MUC2) were scored histologically. i-FABP is involved in fatty acid transport and MUC2 in epithelial protection. A high iron diamine (HID) staining was performed to discriminate between sialo- and sulfomucins. Expression of i-FABP and MUC2 was quantified by Western blotting of biopsy homogenates. Results: Inulin supplementation led to a significantly increased level of butyrate (62% increase) in faeces and clinically led to a decreased PDAI (from 4.39±0.62 to 3.05±0.44; P=0.002). However, inulin supplementation did not improve pouch morphology, nor did it alter the number of MUC2-producing goblet cells or the total amount of mucin MUC2. In addition, the ratio between sialo- and sulfomucins as detected by HID also was not altered by inulin supplementation. However, the expression of the enterocyte-specific i-FABP as wel as the amount of i-FABP expressing cells increased due to the presence of enteral inulin. There is a trend that the amount of i-FABP inversely correlates with the PDAI (R=-0.23, P=0.06), whereas the amount of MUC2 did not correlate with the PDAI (R=0.08, P=0.49). In conclusion: Inulin supplementation led to an increase of butyrate in the pouch, but did not improve morphology nor did it lead to increased epithelial protection as measured by the amount of MUC2. However, clinically inulin supplementation led to a decrease of the PDAI, suggesting that inulin could play a role in the treatment of pouchitis. Since there is a trend that i-FABP, which is exclusively expressed by differentiated enterocytes, inversely correlates with the PDAI, i-FABP might be useful as a biochemical/histological marker for pouchitis.