Endogenous Production of H2S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

Hydrogen sulfide (H2S) has long been associated with the gastrointestinal tract, especially the bacteria-derived H2S present in flatus. Along with evidence from other organ systems, the finding that gastrointestinal tissues are capable of endogenous production of H2S has led to the hypothesis that H2S is an endogenous gaseous signaling molecule. In this review, the criteria of gasotransmitters are reexamined, and evidence from the literature regarding H2S as a gaseous signaling molecule is discussed. H2S is produced enzymatically by gastrointestinal tissues, but evidence is lacking on whether H2S production is regulated. H2S causes well-defined physiologic effects in gastrointestinal tissues, but evidence for a receptor for H2S is lacking. H2S is inactivated through enzymatic oxidation, but evidence is lacking on whether manipulating H2S oxidation alters endogenous cell signaling. Remaining questions regarding the role of H2S as a gaseous signaling molecule in the gastrointestinal tract suggest that H2S currently remains a molecule in search of a physiologic function. Antioxid. Redox Signal. 12, 1135-1146.