Hydrogen Sulfide (H₂S)

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]Liu 2020 — High-Fat Diet Affects Heavy Metal Accumulation and Kidney Toxicity via Gut MicrobiotaLiu, Liu, Liu et al. · 2020Open reference 1 ↓}

Physiological Roles (Low Concentration)#

Vasodilation: H₂S relaxes vascular smooth muscle, complementing nitric oxide—relevant to erectile function.^{[2]Cai 2022 — Gut Microbiota Supports Male Reproduction via Nutrition, Immunity, and SignalingHui Cai, Xuanhong Cao, Dezhe Qin et al. · 2022Open reference 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]The Impact of Ketogenic Diet on Colorectal Cancer Progression and the Co-evolution of Gut Microbiota: A Research ProtocolMelika Shirdarreh, Yasamin Sadeghi, Tina Rahimi · 2021Open reference 3 ↓}

CRC promotion: High H₂S damages DNA and promotes colorectal carcinogenesis. Endometriosis: H₂S activates NF-kB in endometrial stromal cells, promoting Metal-Driven Inflammation and lesion growth.^{[4]H2S promotes proliferation of endometrial stromal cells via activating the NF-kB pathway in endometriosisLei S, Cao Y, Sun J et al. · 2018Open reference 4 ↓} CKD: Altered H₂S metabolism in CKD gut.^{[5]Alterations to the Gut Microbiota and Their Correlation with Inflammatory Factors in CKDFengXia Li, MeiHong Wang, JunPing Wang et al. · 2019Open reference 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.