Effects of Hydrogen Sulfide on the Microbiome: From Toxicity to Therapy

<b><i>Significance:</i></b> Hydrogen sulfide (H₂S), an important regulator of physiology and health, helps resolve inflammation and promotes tissue repair in the gastrointestinal tract. <b><i>Recent Advances:</i></b> Gut microbiota live as a multispecies biofilm in close interaction with the upper mucus layer lining the epithelium. The relative abundance, spatial organization, and function of these microorganisms affect a broad range of health outcomes. This article provides a state-of-the-art review of our understanding of the cross talk between H₂S, the gut microbiota, and health. H₂S can have toxic or therapeutic effects, depending on its concentration and source. When produced at excessive concentrations by local microbiota, H₂S may cause mucus disruption and inflammation and contribute to development of cancer. In contrast, low levels of endogenous or exogenous H₂S directly stabilize mucus layers, prevent fragmentation and adherence of the microbiota biofilm to the epithelium, inhibit the release of invasive pathobionts, and help resolve inflammation and tissue injury. Although scarce, research findings suggest that dietary H₂S obtained from plants or ingestion of the H₂S precursor, L-cysteine, may also modulate the abundance and function of microbiota. <b><i>Critical Issues:</i></b> A critical issue is the lack of understanding of the metagenomic, transcriptomic, and proteomic alterations that characterize the interactions between H₂S and gut microbiota to shape health outcomes. <b><i>Future Directions:</i></b> The ambivalent roles of H₂S in the gut offer a fertile ground for research on such critical issues. The findings will improve our understanding of how H₂S modulates the microbiota to affect body function and will help identify novel therapeutic strategies. <i>Antioxid. Redox Signal</i>. 36, 211-219.