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

Significance: Hydrogen sulfide (H(2)S), an important regulator of physiology and health, helps resolve inflammation and promotes tissue repair in the gastrointestinal tract. Recent Advances: 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 H(2)S, the gut microbiota, and health. H(2)S can have toxic or therapeutic effects, depending on its concentration and source. When produced at excessive concentrations by local microbiota, H(2)S may cause mucus disruption and inflammation and contribute to development of cancer. In contrast, low levels of endogenous or exogenous H(2)S 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 H(2)S obtained from plants or ingestion of the H(2)S precursor, L-cysteine, may also modulate the abundance and function of microbiota. Critical Issues: A critical issue is the lack of understanding of the metagenomic, transcriptomic, and proteomic alterations that characterize the interactions between H(2)S and gut microbiota to shape health outcomes. Future Directions: The ambivalent roles of H(2)S in the gut offer a fertile ground for research on such critical issues. The findings will improve our understanding of how H(2)S modulates the microbiota to affect body function and will help identify novel therapeutic strategies. Antioxid. Redox Signal. 36, 211–219.