Sulfide as a Mucus Barrier-Breaker in Inflammatory Bowel Disease?

The gut epithelium is covered by mucus consisting of mucin polymers connected via disulfide bonds. The mucus layer limits exposure of epithelial cells to toxins and bacteria. A recent study has shown that sulfide, produced by certain bacteria, reduces disulfide bonds in the mucus network. The resulting breaks in the mucus barrier allow exposure of the epithelium to bacteria and toxins, causing inflammation. In this opinion article we argue that this mechanism may be involved in the etiology and/or severity of inflammatory bowel disease (IBD) because IBD is associated with decreased mucus barrier function, altered microbial species, and increased sulfide concentrations. Increasing the mucus integrity by reducing sulfide concentrations in the intestine may be a novel therapeutic option for IBD.

TrendsThe mucus layer lining the colonic epithelium is the first line of defense limiting exposure of epithelial cells to ingested food components, digestive enzymes, and microorganisms.Mucus consists of a network of mucins produced by intestinal goblet cells. The mucins are interconnected via disulfide bonds into large polymeric sheets forming the mucus layer.Hydrogen sulfide, produced by sulfate-reducing bacteria (SRB) and some other bacteria, reduces disulfide bonds present in the mucus network, thereby breaking the mucus barrier.Inflammatory bowel disease (IBD) is characterized by decreased mucus barrier function, which may be due to increased sulfide production by altered microbial species present in IBD patients with active disease.Lowering hydrogen sulfide concentrations in the gut lumen could represent an exciting potential therapeutic strategy for treating IBD.