The Intersection between Tryptophan-Kynurenine Pathway Metabolites and Immune Inflammation, Hormones, and Gut Microbiota in Perinatal Depression

Abstract

Perinatal depression is a prevalent mental disorder among pregnant women, characterized by sleep disturbances, appetite changes, negative emotions, cognitive impairment, and suicidal or homicidal tendencies. These symptoms severely compromise personal well-being, disrupt family life, and burden society. Early detection and intervention are thus crucial. The tryptophan-kynurenine (TRP-KYN) pathway is central to the inflammatory hypothesis of depression and has gained significant attention in perinatal depression research. This pathway encompasses numerous metabolic enzymes and neuroactive metabolites that interact with other physiological systems, influencing neurotransmitter synthesis and neuronal development. Through these interactions, the TRP-KYN pathway exerts psychotropic effects. This article reviews the key metabolites and enzymes of the TRP-KYN pathway and examines its intersection with immune inflammation, hormones, and gut microbiota.

Fig. 1.

Schematic diagram of the TRP-KYN pathway. The diagram illustrates the central role of kynurenine within the TRP-KYN pathway, where it undergoes degradation through three specific routes (via KATs, KYNU, and KMO) to generate various neuroactive metabolites. Abbreviations: TRP, tryptophan; IDO, indoleamine-2,3-dioxygenase; TDO, tryptophan-2,3-dioxygenase; KATs, kynurenine aminotransferase I–III; AA, anthranilic acid; 3-HK, 3-hydroxykynurenine; 3-HAA, 3-hydroxyanthrenillc acid; KMO, kynurenine 3-monooxygenase; HAAO, 3-hydroxyanthranilate 3,4-dioxygenase; XA, xanthurenic acid; ACMS, 2-amino-3-carboxymuconate-6-semialdehyde; ACMSD, ACMS decarboxylase; PA, picolinic acid; QA, quinolinic acid; NAD⁺, nicotinamide adenine dinucleotide; TRP-KYN, tryptophan-kynurenine. Note: The graphics are produced using MedPeer software (V1.3240320, Beijing Maidipel Information Technology Co., Ltd., Beijing, China).

Fig. 2.

Interaction of the TRP-KYN pathway with hormones, inflammation, and gut microbiota. This figure depicts the complex interactions between the TRP-KYN pathway and various physiological processes, including immune inflammation, hormones and gut microbiota. Abbreviations: IDO, indoleamine 2,3-dioxygenase; TDO, tryptophan-2,3-dioxygenase; CNS, central nervous system; SCFAs, short chain fatty acids. Note: The graphics are produced by medpeer software (V1.3240320, Beijing Maidipel Information Technology Co., Ltd., Beijing, China).