Microbial pathways in colonic sulfur metabolism and links with health and disease

Abstract

Sulfur is both crucial to life and a potential threat to health. While colonic sulfur metabolism mediated by eukaryotic cells is relatively well studied, much less is known about sulfur metabolism within gastrointestinal microbes. Sulfated compounds in the colon are either of inorganic (e.g., sulfates, sulfites) or organic (e.g., dietary amino acids and host mucins) origin. The most extensively studied of the microbes involved in colonic sulfur metabolism are the sulfate-reducing bacteria (SRB), which are common colonic inhabitants. Many other microbial pathways are likely to shape colonic sulfur metabolism as well as the composition and availability of sulfated compounds, and these interactions need to be examined in more detail. Hydrogen sulfide is the sulfur derivative that has attracted the most attention in the context of colonic health, and the extent to which it is detrimental or beneficial remains in debate. Several lines of evidence point to SRB or exogenous hydrogen sulfide as potential players in the etiology of intestinal disorders, inflammatory bowel diseases (IBDs) and colorectal cancer in particular. Generation of hydrogen sulfide via pathways other than dissimilatory sulfate reduction may be as, or more, important than those involving the SRB. We suggest here that a novel axis of research is to assess the effects of hydrogen sulfide in shaping colonic microbiome structure. Clearly, in-depth characterization of the microbial pathways involved in colonic sulfur metabolism is necessary for a better understanding of its contribution to colonic disorders and development of therapeutic strategies.

Keywords: colonic microbiota; colorectal cancer; hydrogen sulfide; inflammatory bowel disease; irritable bowel syndrome; sulfate-reducing bacteria; sulfur.

Figure 1

Overview of the microbial pathways involved in colonic sulfur metabolism. The sulfate remaining from assimilatory sulfate reduction is available for sulfate-reducing bacteria and, thus, H₂S production. Taurine and cysteine are additional potentially important substrates for microbial production of H₂S. Various microbial metabolic pathways influence the composition and relative abundance of organic sulfur compounds.

Figure 2

Dissimilatory sulfate reduction pathway. Microbial sulfate reduction relies on sequential catalytic reactions in which reduction of sulfate is coupled with oxidation of H₂ or simple organic molecules. This anaerobic respiration pathway is less favorable thermodynamically than aerobic respiration.

Figure 3

Pathways of cysteine degradation to H₂S. Cysteine desulfhydrase is a key enzyme for initial microbial cysteine fermentation and pyruvate production. However, recent evidence indicates that three other enzymes orthologous to eukaryotic enzymes may catalyze similar reactions. The generation of H₂S via these four enzymatic pathways may surpass that by dissimilatory sulfate reduction, especially in hosts consuming a protein-rich diet.

Figure 4

The taurine degradation pathway of Bilophila wadsworthia. Bilophila wadsworthia is the only known intestinal microbe that uses taurine as an electron acceptor for anaerobic respiration. The first two enzymatic reactions result in sulfite production. Sulfite is subsequently converted to H₂S by a dissimilatory sulfite reductase that differs structurally from those used by sulfate-reducing bacteria.