Sulfide dynamics at the gut-microbiota interface: diet, oxygen and redox interplay

Teeming with microbes, the unique biogeography of the gut is shaped by interactions between diet, host and microbial metabolism. Hydrogen sulfide represents one such plane of interaction in the lower gut where it is largely the product of microbial activity. Sulfide oxidation by host epithelial cells helps shape a severely hypoxic luminal environment in which obligate anaerobes thrive and furnish among other products, butyrate, a fuel of choice for colonocytes. This metabolic symbiosis in healthy gut is supported by diet, and disrupted when the host sulfide oxidation capacity is exceeded, with resultant local and long-range impacts, including increased susceptibility to enteric pathogens and behavioral changes. Under homeostatic conditions, sulfide oxidation tunes host energy and redox metabolism that is corrupted under dysbiosis linked to gastrointestinal diseases. H2S could also be important for inducing a metabolic state change as in hibernating animals, by increasing energy storage in the form of reduced cofactors as well as increasing intracellular oxygen. In this review, we bracket luminal free sulfide exposure to colonocytes based on bioenergetic studies on colon-derived cells, discuss the microbial pathways for sulfide generation, and their interplay with dietary sulfur and host oxygen and redox metabolism.