Gaseous metabolites as therapeutic targets in ulcerative colitis

Abstract

Diet therapies are currently under-utilised in optimising clinical outcomes for patients with active ulcerative colitis (UC). Furthermore, existing dietary therapies are framed by poorly defined mechanistic targets to warrant its success. There is good evidence to suggest that microbial production of gaseous metabolites, hydrogen sulfide (H₂S) and nitric oxide (NO) are implicated in the development of mucosal inflammation in UC. On a cellular level, exposure of the colonic epithelium to excessive concentrations of these gases are shown to promote functional defects described in UC. Hence, targeting bacterial production of these gases could provide an opportunity to formulate new dietary therapies in UC. Despite the paucity of evidence, there is epidemiological and clinical data to support the concept of reducing mucosal inflammation in UC via dietary strategies that reduce H₂S. Several dietary components, namely sulphur-containing amino acids and inorganic sulphur have been shown to be influential in enhancing colonic H₂S production. More recent data suggests increasing the supply of readily fermentable fibre as an effective strategy for H₂S reduction. Conversely, very little is known regarding how diet alters microbial production of NO. Hence, the current evidence suggest that a whole diet approach is needed. Finally, biomarkers for assessing changes in microbial gaseous metabolites in response to dietary interventions are very much required. In conclusion, this review identifies a great need for high quality randomised-controlled trials to demonstrate the efficacy of a sulphide-reducing dietary therapy for patients with active UC.

Keywords: Diet; Ulcerative colitis; Hydrogen sulfide; Nitric oxide; Sulphide-reducing diet

Core Tip: There is room to develop efficacious dietary therapies in ulcerative colitis (UC) by targeting underlying pathogenic mechanisms. Emerging data indicates that dietary factors play a significant role in modulating two gaseous metabolites, hydrogen sulphide and nitric oxide, that affect the integrity of the colonic mucosal barrier in UC. These gases are produced by the colonic microbiota in response to sulphur-containing protein and to a lesser extent, inorganic sulphur (sulphates and sulphites), but suppressed by the presence of fermentable fibre. Preliminary work suggests that a multi-prong diet that targets reduction of these gases have therapeutic potential and further randomised-controlled trials are underway.