Sulfur-Element containing metabolic pathways in human health and crosstalk with the microbiome

In humans, methionine derived from dietary proteins is necessary for cellular homeostasis and regeneration of sulfur containing pathways, which produce inorganic sulfur species (ISS) along with essential organic sulfur compounds (OSC). In recent years, inorganic sulfur species have gained attention as key players in the crosstalk of human health and the gut microbiome. Endogenously, ISS includes hydrogen sulfide (H₂S), sulfite (SO₃^2-), thiosulfate (S₂O₃^2-), and sulfate (SO₄^2-), which are produced by enzymes in the transsulfuration and sulfur oxidation pathways. Additionally, sulfate-reducing bacteria (SRB) in the gut lumen are notable H₂S producers which can contribute to the ISS pools of the human host. In this review, we will focus on the systemic effects of sulfur in biological pathways, describe the contrasting mechanisms of sulfurylation versus phosphorylation on the hydroxyl of serine/threonine and tyrosine residues of proteins in post-translational modifications, and the role of the gut microbiome in human sulfur metabolism.