Colonic sulfide in pathogenesis and treatment of ulcerative colitis.
A role for colonic sulfide in the pathogenesis and treatment of ulcerative colitis (UC) has emerged based on biochemical, microbiological, nutritional, toxicological, epidemiological, and therapeutic evidence. Metabolism of isolated colonic epithelial cells has indicated that the bacterial short-chain fatty acid n-butyrate maintains the epithelial barrier and that sulfides can inhibit oxidation of n-butyrate analogous to that observed in active UC. Sulfur for fermentation in the colon is essential for n-butyrate formation and sulfidogenesis aids disposal of colonic hydrogen produced by bacteria. The numbers of sulfate-reducing bacteria and sulfidogenesis is greater in UC than control cases. Sulfide is mainly detoxified by methylation in colonic epithelial cells and circulating red blood cells. The enzyme activity of sulfide methylation is higher in red blood cells of UC patients than control cases. Patients with UC ingest more protein and thereby sulfur amino acids than control subjects. Removing foods rich in sulfur amino acids (milk, eggs, cheese) has proven therapeutic benefits in UC. 5-Amino salicylic acid reduces fermentative production of hydrogen sulfide by colonic bacteria, and aminoglycosides, which inhibit sulfate-reducing bacteria, are of therapeutic benefit in active UC. Methyl-donating agents are a category of drugs of potential therapeutic use in UC. A correlation between sulfide production and mucosal immune responses in UC needs to be undertaken. Control of sulfidogenesis and sulfide detoxification may be important in the disease process of UC, although whether their roles is in an initiating or promoting capacity has yet to be determined.
Roediger
W E
WE
Colorectal Unit, University of Adelaide, Queen Elizabeth Hospital, Australia.
Moore
J
J
Babidge
W
W
D001419:Bacteria / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000382:microbiology / Q000628:therapy*; D003106:Colon / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D008745:Methylation; D013440:Sulfides / Q000378:metabolism*
D013440:Sulfides; D006862:Hydrogen Sulfide