HISTOLOGICAL-CHANGES IN THE COLONIC MUCOSA FOLLOWING IRRIGATION WITH SHORT-CHAIN FATTY-ACIDS

Objectives: Short-chain fatty acids (SCFAs) derived from bacterial fer mentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. Design: A detailed histological evaluation of colo nic biopsy specimens was performed in patients with active distal ulce rative colitis who were treated with rectal enemas containing a mixtur e of SCFAs, n-butyrate alone or saline placebo. Together with light mi croscopic parameters of mucosal inflammation, the pattern of crypt cel l proliferation (proliferating cell nuclear antigen) and the mucosal a ctivity of factor XIII were assessed. Results: Butyrate reduced the de nsity of polymorphonuclear leucocytes in the lamina propria (4 weeks: P=0.063; 8 weeks: P=0.091); other inflammatory parameters remained unc hanged. Both butyrate and the SCFA mixture reduced significantly the n umber of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower th an in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. Conclusion: SCFAs and butyrate have a more mar ked effect on crypt cell proliferation than on parameters of inflammat ion in patients with active ulcerative colitis.