Microbial regulation of host hydrogen sulfide bioavailability and metabolism

Hydrogen sulfide (H2S), generated through various endogenous enzymatic and nonenzymatic pathways, is emerging as a regulator of physiological and pathological events throughout the body. Bacteria in the gastrointestinal tract also produce significant amounts of H2S that regulates microflora growth and virulence responses. However, the impact of the microbiota on host global H2S bioavailability and metabolism remains unknown. To address this question, we examined H2S bioavailability in its various forms (free, acid labile, or bound sulfane sulfur), cystathionine γ-lyase (CSE) activity, and cysteine levels in tissues from germ-free versus conventionally housed mice. Free H2S levels were significantly reduced in plasma and gastrointestinal tissues of germ-free mice. Bound sulfane sulfur levels were decreased by 50-80% in germ-free mouse plasma and adipose and lung tissues. Tissue CSE activity was significantly reduced in many organs from germ-free mice, whereas tissue cysteine levels were significantly elevated compared to conventional mice. These data reveal that the microbiota profoundly regulates systemic bioavailability and metabolism of H2S.