INCREASED FECAL MUCIN SULFATASE ACTIVITY IN ULCERATIVE-COLITIS - A POTENTIAL TARGET FOR TREATMENT

Colonic mucin is heavily sulphated and it has been shown that enzymati c desulphation by faecal bacterial sulphatases greatly increases its s usceptibility to degradation by faecal glycosidases. A possible role f or faecal mucin sulphatase in the pathogenesis of inflammatory bowel d isease has therefore been explored. Faecal mucin sulphatase activity a ssayed using S-35 mucin as substrate was increased in ulcerative colit is (median 80.2 units/g pellet weight (range 6.9-1063; 95% confidence intervals (CI): 45.2 to 293.8, n=22) compared with 11.3 units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n=17) in healthy controls (p<0.01), wh ere one unit released 1000 dpm free sulphate/hour from S-35 mucin (168 0 dpm/mu g). Patients with active ulcerative colitis had higher sulpha tase activity (median 146; 95% CI: 98 to 253 units/g, n=10) than those with inactive ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units /g, n=12) (p<0.05). Longitudinal studies in patients with ulcerative c olitis show fluctuations of faecal mucin sulphatase activity correspon ding to clinical disease activity in six of seven patients. Faecal muc in sulphatase activity was not significantly increased in Crohn's dise ase (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3 units/g, n=14) . The bismuth salts, bismuth subcitrate and bismuth subsalicylate were found to inhibit faecal mucin sulphatase activity at concentrations a chievable therapeutically. The increased faecal mucin sulphatase activ ity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment.