Increased faecal mucin sulphatase activity in ulcerative colitis: a potential target for treatment.
Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate was increased in ulcerative colitis (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), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680 dpm/microgram). Patients with active ulcerative colitis had higher sulphatase 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 colitis show fluctuations of faecal mucin sulphatase activity corresponding to clinical disease activity in six of seven patients. Faecal mucin sulphatase activity was not significantly increased in Crohn's disease (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 achievable therapeutically. The increased faecal mucin sulphatase activity 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.
Tsai
H H
HH
Department of Medicine, University of Liverpool.
Dwarakanath
A D
AD
Hart
C A
CA
Milton
J D
JD
Rhodes
J M
JM
D000328:Adult; D000368:Aged; D001729:Bismuth / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000201:enzymology*; D003424:Crohn Disease / Q000201:enzymology; D005243:Feces / Q000201:enzymology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000627:therapeutic use; D012459:Salicylates / Q000627:therapeutic use; D013429:Sulfatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000520:alpha-Glucosidases / Q000032:analysis
D009942:Organometallic Compounds; D012459:Salicylates; C015715:bismuth subsalicylate; D013429:Sulfatases; C074449:mucin sulfatase; D000520:alpha-Glucosidases; C002791:bismuth tripotassium dicitrate; D001729:Bismuth