Tryptophan Metabolism in Developmental Origins of Health and Disease

Tryptophan, an essential amino acid in mammals that is obtained from the diet, has impacts on early life and development. This amino acid is being studied under the Developmental Origins of Health and Disease (DOHaD) concept, which has led to findings of factors from conception to early childhood that affect health and susceptibility to disease. Tryptophan is metabolized mainly through 2 pathways, serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system. Serotonin also regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include trp-2,3-dioxygenase (TDO) and indoleamine-2,3-dioxygenase (IDO) in the kynurenine pathway and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2) in the serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, which is rich in tryptophan and protective bioactive molecules. Tryptophan, derived solely from breast milk, is crucial for infants. Its levels are high in newborns, 2-4 times higher than in adults during the first 3 weeks postpartum, and then gradually declining to adult levels by the fourth week. Due to the remarkable role of tryptophan in organic development, disturbances in tryptophan metabolism at different life stages, fetal or postnatal, may lead to modifications of its metabolism related to pathological states in adult life. We bring some of this evidence to this review.