title: Effects of metronidazole and oligofructose on faecal concentrations of sulphate-reducing bacteria and their activity in human volunteers.
abstract: OBJECTIVE
  Sulphate-reducing bacteria (SRB) have been implicated in the aetiology of ulcerative colitis. Sulphide produced from reduction of sulphate by SRB is highly toxic to colonocytes and can impair their metabolic function. The aim of this study was to investigate the modulation of the colonic bacterial flora using metronidazole and the prebiotic oligofructose on the concentration and activity of SRB.
  
  
  METHODS
  Healthy volunteers were randomly allocated to take metronidazole (5 days), oligofructose (12 days) or both metronidazole (5 days) and oligofructose (12 days). At days 0, 5, 12 and 19, stool samples were cultured, and their pH measured; concentrations of sulphate, hydrogen sulphide, short-chain fatty acids (SCFAs) were measured and the sulphate reduction rates (SRRs) determined.
  
  
  RESULTS
  In SRB-positive volunteers (n=16) faecal SRB concentrations fell with metronidazole (95% CI, 2.19, 3.36 p<0.0001) even when combined with oligofructose (95% CI 2.32, 4.01 p<0.0001). Faecal anaerobe concentrations fell with metronidazole and bifidobacterial concentrations rose with oligofructose irrespective of SRB status. Faecal SRRs fell with metronidazole irrespective of the presence of faecal SRB (95% CI 29.0, 56.1 p<0.0001). No changes in faecal sulphate concentrations were seen. Faecal hydrogen sulphide concentrations fell with oligofructose in SRB-positive volunteers (95% CI 0.14, 0.53 p=0.002). Faecal SCFA concentrations fell with metronidazole (-103.7, -19.6, p=0.007) and rose with oligofructose (9.9, 83.1 p=0.016).
  
  
  CONCLUSIONS
  The study shows that metronidazole, but not oligofructose, reduced the concentration and activity of faecal SRB. This reduction had no impact on faecal concentrations of sulphate and hydrogen sulphide, suggesting that other methods of hydrogen sulphide production are more important. Oligofructose causes a reduction in faecal hydrogen sulphide, and an increase in SCFA concentrations may thus have a therapeutic role in patients with ulcerative colitis.
authors.affiliation: Department of Gastroenterology, Derriford Hospital, Plymouth, Devon PL6 8DH, UK. sjl@doctors.org.uk
authors.forename: Stephen
authors.initials: S
authors.lastname: Lewis
authors.forename: Jon
authors.initials: J
authors.lastname: Brazier
authors.forename: David
authors.initials: D
authors.lastname: Beard
authors.forename: Nazeem
authors.initials: N
authors.lastname: Nazem
authors.forename: Douglas
authors.initials: D
authors.lastname: Proctor
mesh_terms: D000328:Adult; D003106:Colon / Q000187:drug effects / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005243:Feces / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage*; D009844:Oligosaccharides / Q000008:administration & dosage*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016999:Sulfur-Reducing Bacteria / Q000187:drug effects* / Q000302:isolation & purification*
chemical_list: D009844:Oligosaccharides; C120489:oligofructose; D008795:Metronidazole