Get access

Decreased mucosal sulfide detoxification is related to an impaired butyrate oxidation in ulcerative colitis

Authors

  • Vicky De Preter PhD,

    1. Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
    Search for more papers by this author
  • Ingrid Arijs PhD,

    1. Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
    Search for more papers by this author
  • Karen Windey MSc,

    1. Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
    Search for more papers by this author
  • Wiebe Vanhove BSc,

    1. Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
    Search for more papers by this author
  • Severine Vermeire MD, PhD,

    1. Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
    Search for more papers by this author
  • Frans Schuit PhD,

    1. Gene Expression Unit, Department of Molecular Cell Biology, KULeuven, Leuven, Belgium
    Search for more papers by this author
  • Paul Rutgeerts MD, PhD,

    1. Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
    Search for more papers by this author
  • Kristin Verbeke PhD

    Corresponding author
    1. Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, KULeuven, Leuven, Belgium
    • Translational Research Center for Gastrointestinal Disorders (TARGID), O&N 1, box 701, Herestraat 49, 3000 Leuven, Belgium
    Search for more papers by this author

Abstract

Background:

Defective detoxification of sulfides leads to damage to the mucosa and may play a role in the etiology of ulcerative colitis (UC). The colonic mucosal thiosulfate sulfurtransferase (TST) enzyme removes H2S by conversion to the less toxic thiocyanate. In this study we measured colonic mucosal TST enzyme activity and gene expression in UC and controls. In addition, the influence of sulfides on butyrate oxidation was evaluated.

Methods:

Colonic mucosal biopsies were collected from 92 UC patients and 24 controls. TST activity was measured spectrophotometrically. To assess gene expression, total RNA from biopsies was used for quantitative reverse-transcription polymerase chain reaction (RT-PCR). In 20 UC patients, gene expression was reassessed after their first treatment with infliximab. To evaluate the effect of sulfides on butyrate oxidation, biopsies were incubated with 1.5 mM NaHS.

Results:

TST enzyme activity and gene expression were significantly decreased in UC patients vs. controls (P < 0.001). UC patients, classified into disease activity subgroups, showed a significantly decreased TST activity and gene expression in the subgroups as compared to healthy subjects (P < 0.05 for all). In 20 patients, gene expression was reassessed after their first infliximab therapy. In responders to infliximab, a significant increase in TST gene expression was observed. However, TST mRNA levels did not return to control values after therapy in the responders. In controls, but not in UC, sulfide significantly decreased butyrate oxidation.

Conclusions:

We found an impaired detoxification mechanism of sulfide at TST protein and RNA level in UC. Inflammation was clearly associated with the observed TST deficiency. (Inflamm Bowel Dis 2012;)

Get access to the full text of this article

Ancillary