Fig. 3

Scheme showing tryptophan metabolism and its interaction with gut microbiota and EFAs. Legend to Figure 3. Indoles are synthesized from tryptophan by gut microbiota that express tryptophanase. Indolepropionic acid (IPA) synthesized by gut microbiota is a neuroprotective substance that binds to several receptors, including the pregnane X receptor (PXR) in intestinal cells, to facilitate mucosal homeostasis. IPA is absorbed from the gut and transferred to the brain, where it prevents β-amyloid fibril formation. Tryptophan is metabolized to indole-3-aldehyde (I3A) by gut microbiota acts on the aryl hydrocarbon receptor (AhR) in intestinal immune cells. Gut microbiota act (i) directly on enterochromaffin (EC) cells to increase colonic tryptophan hydroxylase 1 (Tph1) expression and promote serotonin synthesis; (ii) alter host by virtue of their metabolites, including short chain fatty acids, tryptophan, tryptamine, and secondary bile acids; (iii) short chain fatty acids (SCFAs) stimulate serotonin synthesis and release by acting on enterochromaffin cells; (iv) tryptophan metabolism is regulated by the gut microbiota and thus, the gut microbiota influences serotonin metabolism; and (v) tryptamine is a ligand for the 5-HT₄ receptor (5-HT₄R) and secondary bile acids, formed by the gut microbiota promote Tph1 expression and stimulate serotonin synthesis [88].