Dietary Factors in Sulfur Metabolism and Pathogenesis of Ulcerative Colitis

Abstract

The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to the dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.

Altered Gut Archaea Composition and Interaction With Bacteria Are Associated With Colorectal Cancer

“…13 It was hypothesized that reduction in hydrogen concentrations by gut methanogens results in lower production of hydrogen sulfite by sulfatereducing bacteria, thus reducing potential damage to colonic epithelial cells. 41 Also, native Africans with high levels of methanogenic archaea are reportedly less susceptible to sporadic CRC. 42 Therefore, the depletion of methanogens in the gut, as identified in this study, may favor colon carcinogenesis.…”

Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis

“…119 Similarly, in an ongoing trial for ulcerative colitis we have chosen to select donors that have the lowest relative abundances of sulphate-reducing bacteria, which are hypothesised to be an important source of hydrogen sulphide that may be involved in the pathogenesis of ulcerative colitis (Clinical Trial: NCT03948919). 120 These examples demonstrate that it is possible to stratify donor microbiota using rational and testable hypotheses, which can advance IMT development toward next-generation products that have the potential for greater efficacy.…”

Manipulating resident microbiota to enhance regulatory immune function to treat inflammatory bowel diseases

“…Moreover, dysbiosis alters microbial metabolites in the intestine. For example, hydrogen sulfide, a dietary metabolite, is a toxin associated with progression of mucosal inflammation in UC by blocking butyrate metabolism in colonic epithelial cells [55]. Defective detoxification capacity may be involved in the pathogenesis of UC [55].…”

“…For example, hydrogen sulfide, a dietary metabolite, is a toxin associated with progression of mucosal inflammation in UC by blocking butyrate metabolism in colonic epithelial cells [55]. Defective detoxification capacity may be involved in the pathogenesis of UC [55]. Trimethylamine-N-oxide (TMAO) is generated by enteric anaerobes through the digestion of dietary carnitine and phosphatidylcholine [56].…”

“…Western diets (enriched in fat, phosphatidylcholine, and L-carnitine) potentially promote mucosal inflammation through TMAO induction [57]. Both hydrogen sulfide and TMAO are increased in the feces of IBD patients [55,56]. In contrast, multiple bacterial metabolites exert protective activities that stimulate mucosal homeostasis.…”