The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis

Abstract

Background: Butyrate oxidation within the colonocyte is selectively inhibited by hydrogen sulphide, reproducing the metabolic lesion observed in active ulcerative colitis.

Aims: To study generation of hydrogen sulphide by sulphate reducing bacteria (SRB) and the effects of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis in order to identify a role of this noxious agent in pathogenesis.

Patients: Fresh faeces were obtained from 37 patients with ulcerative colitis (23 with active disease) and 16 healthy controls.

Methods: SRB were enumerated from fresh faecal slurries and measurements made of sulphate reducing activity, and sulphate and hydrogen sulphide concentrations. The effect of 5-ASA on hydrogen sulphide production was studied in vitro.

Results: All controls and patients with active ulcerative colitis carried SRB and total viable counts were significantly related to the clinical severity grade. SRB were of two distinct types: rapidly growing strains (desulfovibrios) which showed high sulphate reduction rates, present in 30% of patients with ulcerative colitis and 44% of controls; and slow growing strains which had little activity. In vitro, 5-ASA inhibited sulphide production in a dose dependent manner; in patients with ulcerative colitis not on these drugs faecal sulphide was significantly higher than in controls (0.55 versus 0.25 mM, p=0.027).

Conclusions: Counts and carriage rates of SRB in faeces of patients with ulcerative colitis are not significantly different from those in controls. SRB metabolism is not uniform between strains and alternative sources of hydrogen sulphide production exist in the colonic lumen which may be similarly inhibited by 5-ASA. The evidence for hydrogen sulphide as a metabolic toxin in ulcerative colitis remains circumstantial.

Figures

Figure 1

Box and whisker plots of total viable counts of sulphate reducing bacteria (SRB) related to (A) Truelove and Witts global clinical grade, and (B) sigmoidoscopic grade of mucosal inflammation in patients with ulcerative colitis (Spearman rank correlation test, p

Figure 2

Box and whisker plot showing sulphate reduction rates in faeces of all subjects (patients and healthy controls combined) according to colonial growth characteristics of sulphate reducing bacteria (SRB). Rapidly growing SRB are desulfovibrio-like.

Figure 3

Dose response effect of 5-aminosalicylic acid (5-ASA) on dissimilatory sulphate reduction by sulphate reducing bacteria in faecal slurries. Values are mean (SE) for seven healthy subjects selected with high basal sulphate reducing activity.

Figure 4

Box and whisker plot showing total faecal sulphide concentration in patients with ulcerative colitis (UC) (n=8) not receiving 5-aminosalicylic acid, and healthy controls (n=16).

Figure 5

Box and whisker plots showing total faecal sulphide concentration in patients with ulcerative colitis (n=37) grouped according to treatment with oral drug therapy. (A) Sulphide concentrations in patients treated with 5-aminosalicylic acid (5-ASA) drugs alone or in combination with prednisolone (n=29) versus no 5-ASA (n=8). (B) Sulphide concentrations in patients treated with prednisolone alone or in combination with 5-ASA (n=11) versus no prednisolone (n=26).