Hydrogen Sulfide (H₂S)

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

References (6)

  1. Liu, Liu, Liu et al. (2020). Liu 2020 — High-Fat Diet Affects Heavy Metal Accumulation and Kidney Toxicity via Gut Microbiota. Frontiers in Microbiology. doi:10.3389/fmicb.2020.01604
  2. Hui Cai, Xuanhong Cao, Dezhe Qin et al. (2022). Cai 2022 — Gut Microbiota Supports Male Reproduction via Nutrition, Immunity, and Signaling. Frontiers in Microbiology. doi:10.3389/fmicb.2022.977574
  3. Melika Shirdarreh, Yasamin Sadeghi, Tina Rahimi (2021). The Impact of Ketogenic Diet on Colorectal Cancer Progression and the Co-evolution of Gut Microbiota: A Research Protocol. URNCST Journal. doi:10.26685/urncst.223
  4. Lei S, Cao Y, Sun J et al. (2018). H2S promotes proliferation of endometrial stromal cells via activating the NF-kB pathway in endometriosis. American Journal of Translational Research. doi:10.1186/s13287-018-1015-x
  5. FengXia Li, MeiHong Wang, JunPing Wang et al. (2019). Alterations to the Gut Microbiota and Their Correlation with Inflammatory Factors in CKD. Frontiers in Cellular and Infection Microbiology. doi:10.3389/fcimb.2019.00206
  6. Ji Sung Shim, Dae Hee Kim, Jae Hyun Bae et al. (2016). Shim 2016 — Omega-3 Fatty Acids Improve Erectile Function in Atherosclerosis-induced Chronic Pelvic Ischemia Rat Model. Journal of Korean Medical Science. doi:10.3346/jkms.2016.31.4.585

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