Overview
Hydrogen sulfide is a gaseous signaling molecule (gasotransmitter) produced by both host enzymes (CBS, CSE, 3-MST) and gut bacteria — primarily sulfate-reducing bacteria (desulfovibrio). Like nitric oxide and carbon monoxide, H₂S has dual roles: physiological signaling at low concentrations and cytotoxicity at high concentrations. This concentration-dependent duality makes H₂S a critical node in the metal-microbiome-disease axis.
Microbial H₂S Production
- desulfovibrio and other sulfate-reducing bacteria (SRB) are the primary microbial H₂S sources, reducing dietary sulfate to H₂S as a terminal electron acceptor.
- Protein-rich and high-sulfur amino acid diets increase colonic H₂S production.
- High-fat diets combined with metal exposure amplify SRB abundance and H₂S production [1].
Physiological Roles (Low Concentration)
- Vasodilation: H₂S relaxes vascular smooth muscle, complementing nitric oxide — relevant to erectile function [2].
- Anti-inflammatory: Inhibits NF-kB at physiological concentrations.
- Cytoprotection: Maintains mitochondrial electron transport chain function.
Pathological Roles (High Concentration)
- Colonocyte toxicity: Excess H₂S inhibits cytochrome c oxidase (complex IV) in colonocytes, impairing butyrate oxidation — the energy source for colonic epithelium [3].
- CRC promotion: High H₂S damages DNA and promotes colorectal carcinogenesis.
- Endometriosis: H₂S activates NF-kB in endometrial stromal cells, promoting inflammation and lesion growth [4].
- CKD: Altered H₂S metabolism in CKD gut [5].
Metal Connection
- H₂S binds and precipitates heavy metals (forming insoluble metal sulfides), potentially serving as a detoxification mechanism in the gut — but this also alters metal bioavailability for the microbiome.
- Iron-sulfur cluster enzymes throughout the microbiome are sensitive to H₂S levels.
Cross-References
- desulfovibrio — primary microbial H₂S producer
- colorectal cancer — H₂S-driven colonocyte damage and carcinogenesis
- endometriosis — H₂S/NF-kB amplification loop
- oxidative stress — H₂S as both antioxidant and pro-oxidant
- iron — iron-sulfide precipitation affecting metal ecology