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 bac-terial counts in pouch contents to determine whether hy-drogen sulfide production correlates with pouchitis.
METHODS
During incubation at 37°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 μmol g−1 4 h−1) or had occurred in the past year (4.71 ± 0.41 μmol g−1 4 h−1) was significantly higher (P < 0.05) than when pouchitis had never occurred (1.71 ± 0.43 μmol g−1 4 h−1) or had been inactive in the past year (2.62 ± 0.49 μmol g−1 4 h−1). Antibiotic therapy was associated with very low hydrogen sulfide release (0.68 ± 0.29 μmol g−1 4 h−1). Pouch contents from familial adenomatous polyposis patients produced significantly less hydrogen sulfide (0.75 ± 0.09 μmol 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.
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ACKNOWLEDGMENTS
The authors thank Dr. Brett T. Gemlo, Dr. Richard E. Karulf, Dr. Ann C. Lowry, and Dr. Michael P. Spencer for their help to recruit their patients with this study.
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Supported by The International Research Scholarship of the Research Foundation, The American Society of Colon and Rectal Surgeons, and Minnesota Colon and Rectal Foundation.
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Ohge, H., Furne, J., Springfield, J. et al. Association Between Fecal Hydrogen Sulfide Production and Pouchitis. Dis Colon Rectum 48, 469–475 (2005). https://doi.org/10.1007/s10350-004-0820-8
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DOI: https://doi.org/10.1007/s10350-004-0820-8