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Review
. 2021 Jun 14;18(1):135.
doi: 10.1186/s12974-021-02175-2.

Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease

Li-Ming Chen  1   2 , Chun-Hui Bao  3   4 , Yu Wu  1 , Shi-Hua Liang  5 , Di Wang  1 , Lu-Yi Wu  2 , Yan Huang  2 , Hui-Rong Liu  1   2 , Huan-Gan Wu  6   7
Affiliations
Review

Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease

Li-Ming Chen et al. J Neuroinflammation. .

Abstract

Inflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.

Keywords: Depression; IDO; Inflammatory bowel disease; The brain-gut axis; Tryptophan-kynurenine metabolic pathway.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The tryptophan-kynurenine metabolic pathway. TRP, tryptophan; IDO, indoleamine 2,3-dioxygenase; TDO, tryptophan 2,3-dioxygenase; N-fKYN, N-formyl-kynurenine; AA, anthranilate acid; KYNU, kynureninase; KYN, kynurenine; KAT, kynurenine aminotransferase; KYNA, kynerunic acid; KMO, kynurenine 3-monooxygenase; 3-HK, 3-hydroxykynurenine; HAAH, 3-hydroxyanthranilic acid 3,4-hydroxylase; 3-HAA, 3-hydroxyanthranilic acid; HAAO, 3-hydroxyanthranilicacid 3,4-dioxygenase; AMS, 2-aminomuconic-6-semialdehyde; ACMSD, 2-amino-3-carboxymuconate-6-semialdehydedecarboxylase; ACMS, 2-amino-3-carboxymuconate-6-semialdehyde; AMSD, 2-aminomuconic-6-semialdehyde dehydrogenase; QUIN, quinolinic acid; QPRT, quinolinate phosphoribosyltransferase; PIC, picolinic acid; NAD+, nicotinamide-adenine-dinucleotide
Fig. 2
Fig. 2
The link between intestinal inflammation, KP, and depression in IBD. In the process of IBD, inflammatory activity stimulates intestinal cells to produce a series of inflammatory cytokines such as IFN-γ, IL-6, and IL-1. Activation of IDO by inflammatory cytokines results in increased degradation of TRP to KYN, which crosses the blood-brain barrier and is metabolized by different branches to QUIN and KYNA. In an inflammatory environment, a higher rate of production of neurotoxic molecules such as QUIN, 3-HK, and 3-HAA may cause depression by damaging hippocampal neurons. In contrast, KYNA is a neuroprotective factor. These KP metabolites affect the mood of IBD patients through a complex series of neurobiological responses. IFN, interferon; IL, interleukin; α7nAChRs, α7 nicotinic acetylcholine receptors; Glu, glutamate; NMDA, N-methyl-D-aspartate
See this image and copyright information in PMC

References

    1. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015;12(12):720–727. doi: 10.1038/nrgastro.2015.150. - DOI - PubMed
    1. Wang Y, Ouyang Q, APDW 2004 Chinese IBD working group Ulcerative colitis in China: retrospective analysis of 3100 hospitalized patients. J Gastroenterol Hepatol. 2007;22:1450–1455. doi: 10.1111/j.1440-1746.2007.04873.x. - DOI - PubMed
    1. Ng SC, Leung WK, Shi HY, Li MKK, Leung CM, Ng CKM, Lo FH, Hui YT, Tsang SWC, Chan YK, Loo CK, Chan KH, Hui AJ, Chow WH, Harbord M, Ching JYL, Lee M, Chan V, Tang W, Hung IFN, Ho J, Lao WC, Wong MTL, Sze SF, Shan EHS, Lam BCY, Tong RWH, Mak LY, Wong SH, Wu JCY, Chan FKL, Sung JJY. Epidemiology of inflammatory bowel disease from 1981 to 2014: results from a territory-wide population-based registry in Hong Kong. Inflamm Bowel Dis. 2016;22(8):1954–1960. doi: 10.1097/MIB.0000000000000846. - DOI - PubMed
    1. Zhai H, Liu A, Huang W, Liu X, Feng S, Wu J, Yao Y, Wang C, Li Q, Hao Q, Hu J, Zhang S. Increasing rate of inflammatory bowel disease: a 12-year retrospective study in NingXia, China. BMC Gastroenterol. 2016;16(1):2. doi: 10.1186/s12876-015-0405-0. - DOI - PMC - PubMed
    1. Kaplan GG, Ng SC. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology. 2017;152:313–321.e2. doi: 10.1053/j.gastro.2016.10.020. - DOI - PubMed

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