Association between fecal hydrogen sulfide production and pouchitis.

PURPOSE: The beneficial effect of antibiotics in pouchitis suggests that an unidentified fecal bacterial product causes this condition. A candidate compound is hydrogen sulfide, a highly toxic gas produced by certain fecal bacteria, which causes tissue injury in experimental models. We investigated hydrogen sulfide release and sulfate-reducing bacterial counts in pouch contents to determine whether hydrogen sulfide production correlates with pouchitis.
METHODS: During incubation at 37 degrees C, the production of hydrogen sulfide, methylmercaptan, carbon dioxide, and hydrogen were studied using fresh fecal specimens obtained from 50 patients with ileoanal pouches constructed after total proctocolectomy for ulcerative colitis (n = 45) or for familial adenomatous polyposis (n = 5). Patients with ulcerative colitis were divided into five groups: a) no history of pouchitis (pouch for at least 2 years; n = 8); b) past episode(s) of pouchitis but no active disease for the previous year (n = 9); c) pouchitis in the past year but presently inactive (n = 9); d) ongoing antibiotic treatment (metronidazole or ciprofloxacin) for pouchitis (n = 11); e) currently suffering from pouchitis (n = 8).
RESULTS: Release of hydrogen sulfide when pouchitis was active (6.06 +/- 1.03 micromol g(-1) 4 h(-1)) or had occurred in the past year (4.71 +/- 0.41 pmol g(-1) 4 h(-1)) was significantly higher (P < 0.05) than when pouchitis had never occurred (1.71 +/- 0.43 micromol g(-1) 4 h(-1)) or had been inactive in the past year (2.62 +/- 0.49 micromol g(-1) 4 h(-1)). Antibiotic therapy was associated with very low hydrogen sulfide release (0.68 +/- 0.29 micromol g(-1) 4 h(-1)). Pouch contents from familial adenomatous polyposis patients produced significantly less hydrogen sulfide (0.75 +/- 0.09 micromol g(-1) 4 h(-1)) than did any group of nonantibiotic-treated ulcerative colitis patients. Sulfate-reducing bacterial counts in active pouchitis (9.5 +/- 0.5 log10/g) were significantly higher than in those who never experienced pouchitis (7.38 +/- 0.32 log10/g), and these counts fell dramatically with antibiotic treatment. No statistically significant differences in carbon dioxide and hydrogen were observed among the groups not receiving antibiotics.
CONCLUSIONS: Pouch contents of patients with ongoing pouchitis or an episode within the previous year released significantly more hydrogen sulfide than did the contents of patients who never had an attack of pouchitis and those with longstanding inactive disease. The response to therapy with metronidazole or ciprofloxacin was associated with marked reductions in hydrogen sulfide release and sulfate-reducing bacteria. These results provide a rationale for additional studies to determine whether the high sulfide production is a cause or effect of pouchitis. The lower hydrogen sulfide production by pouch contents of familial adenomatous polyposis vs. patients with ulcerative colitis suggests a fundamental difference in gut sulfide metabolism that could have implications for the etiology of ulcerative colitis as well as the pouchitis of patients with ulcerative colitis.