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Ulcerative colitis may be associated with impaired sulfide detoxification
Patients with ulcerative colitis may have a defective mucosal mechanism for the detoxification of hydrogen sulfide, according to recent study results.
“Previously, we studied the metabolism of butyrate in healthy controls and ulcerative colitis [UC] patients,” Vicky De Preter, PhD, postdoctoral researcher at Translational Research Center for Gastrointestinal Disorders in Leuven, Belgium, told Healio.com. “Because in vitro and in vivo studies have demonstrated that the butyrate oxidation in colonocytes can be inhibited by hydrogen sulfide, thereby reproducing lesions reported in ulcerative colitis, we looked further into the S-mechanism in the gut.”
Researchers collected colonic mucosal biopsies from 92 patients with ulcerative colitis, as well as 24 from a control group. The activity of colonic mucosal enzyme thiosulfate sulfurtransferase (TST) was measured, as well as TST gene expression. Biopsy specimens also were incubated with 1.5 mM NaHS to determine the effect of sulfides on butyrate oxidation.
A positive correlation was found between mRNA TST levels and TST enzyme activity (P<.001), and both TST enzyme activity and TST gene expression were lower among specimens from patients with UC compared with those from the control group (P<.001). A negative correlation was found between mRNA levels and inflammation as indicated by IL-8 mRNA levels (P<.001).
After initial treatment with infliximab, 20 patients with UC had their gene expressions reassessed, with the results indicating increased expression among those responsive to treatment. Relative TST mRNA levels increased from 0.49 (0.44-0.57) to 1.03 (0.82-1.37) (P=.028) among responsive patients with UC, but levels remained lower than those in the control group (P<.001).
Investigators also found that specimens from the control group had decreased butyrate oxidation following incubation with NaHS (P=.003), but those from the colitis group did not. The oxidation rate remained significantly higher among specimens from the control group compared with those from the colitis group despite the decrease (P<.001).
“Patients with ulcerative colitis have, besides an impaired mucosal butyrate metabolism, a defective mucosal detoxification mechanism for hydrogen sulfide,” De Preter said, “and this deficiency is initiated at the gene expression level, not at the functional level. … Abnormal metabolism and functions of H2S and butyrate have both been linked to … UC and colon cancer. However, more studies are necessary to evaluate their roles in a human setting.”