Fig. 1

Molecular mechanisms of action of indole and its metabolites on host physiology and disease. Tryptophan in the colonic lumen is catabolized by bacteria to yield indole and indole derivatives. Indole-3-propionate (IPA) acts on intestinal cells via pregnane X receptors (PXR) to maintain mucosal homeostasis and barrier function. IPA can also act on other organs such as the brain, where it confers neuroprotective effects against ischemia-induced neuronal damage or against Alzheimer’s disease. Indole-3-aldehyde (I3A) acts on the aryl hydrocarbon receptor (AhR) found on intestinal immune cells and increases interleukin-22 (IL-22) production. Activation of AhR plays a crucial role in gut immunity, such as in maintaining the epithelial barrier function and promoting immune tolerance to promote microbial commensalism while protecting against pathogenic infections. Indole has a number of roles, such as a signaling molecule to intestinal L cells to produce glucagon-like protein 1 (GLP-1) or as a ligand for AhR. Indole is also metabolized by the liver to indoxyl sulfate, where an excess is detrimental to human health. Accumulation of indoxyl sulfate in physiologic fluid is toxic and associated with vascular disease and renal dysfunction. AST-120, an orally administered intestinal sorbent, adsorbs indole and decreases serum concentrations of indoxyl sulfate, and is a potential treatment for managing chronic kidney disease