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

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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.

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Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease

Harry Sokol, Julien Planchais, Allison Agus (2018)

The gut microbiota is a crucial actor in human physiology. Many of these effects are mediated by metabolites that are either produced by the microbes or derived from the transformation of environmental or host molecules. Among the array of metabolites at the interface between these microorganisms and the host is the essential aromatic amino acid tryptophan (Trp). In the gut, the three major Trp metabolism pathways leading to serotonin (5-hydroxytryptamine), kynurenine (Kyn), and indole derivatives are under the direct or indirect control of the microbiota. In this review, we gather the most recent advances concerning the central role of Trp metabolism in microbiota-host crosstalk in health and disease. Deciphering the complex equilibrium between these pathways will facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.

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The global burden of IBD: from 2015 to 2025.

Gilaad Kaplan (2015)

Over 1 million residents in the USA and 2.5 million in Europe are estimated to have IBD, with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients. The majority of patients are diagnosed early in life and the incidence continues to rise; therefore, the effect of IBD on health-care systems will rise exponentially. Moreover, IBD has emerged in newly industrialized countries in Asia, South America and Middle East and has evolved into a global disease with rising prevalence in every continent. Understanding the worldwide epidemiological patterns of IBD will prepare us to manage the burden of IBD over time. The goal of this article is to establish the current epidemiology of IBD in the Western world, contrast it with the increase in IBD in newly industrialized countries and forecast the global effects of IBD in 2025.

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Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism

P. Zheng, B. Zeng, C. Zhou … (2016)

Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.

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Author and article information

Contributors

Chun-Hui Bao:

ORCID: http://orcid.org/0000-0002-9763-0046

baochunhui@shutcm.edu.cn

Huan-Gan Wu: wuhuangan@shutcm.edu.cn

Journal

Journal ID (nlm-ta): J Neuroinflammation

Journal ID (iso-abbrev): J Neuroinflammation

Title: Journal of Neuroinflammation

Publisher: BioMed Central (London )

ISSN (Electronic): 1742-2094

Publication date (Electronic): 14 June 2021

Publication date PMC-release: 14 June 2021

Publication date Collection: 2021

Volume: 18

Electronic Location Identifier: 135

Affiliations

[1 ]GRID grid.412540.6, ISNI 0000 0001 2372 7462, Yueyang Hospital of Integrated Chinese and Western Medicine, , Shanghai University of Traditional Chinese Medicine, ; No.110 Ganhe Road, Shanghai, 200437 China

[2 ]GRID grid.412540.6, ISNI 0000 0001 2372 7462, Key Laboratory of Acupuncture and Immunological Effects, , Shanghai University of Traditional Chinese Medicine, ; No. 650 South Wanping Road, Shanghai, 200030 China

[3 ]GRID grid.4830.f, ISNI 0000 0004 0407 1981, Faculty of Economics and Business, , University of Groningen, ; Nettelbosje 2, Groningen, 9747 AE The Netherlands

Author information

Chun-Hui Bao http://orcid.org/0000-0002-9763-0046

Article

Publisher ID: 2175

DOI: 10.1186/s12974-021-02175-2

PMC ID: 8204445

PubMed ID: 34127024

SO-VID: 01b46fd0-e3e6-40c4-912e-72bbfb031e1c

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Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 16 November 2020

Date accepted : 13 May 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81973955

Award ID: 82074546

Award Recipient : Yan Huang

Funded by: FundRef http://dx.doi.org/10.13039/501100013105, Shanghai Rising-Star Program;

Award ID: 19QA1408100

Funded by: FundRef http://dx.doi.org/10.13039/501100010876, Shanghai University of Traditional Chinese Medicine;

Award ID: JY611.27.01.06

Funded by: FundRef http://dx.doi.org/10.13039/501100012166, National Basic Research Program of China (973 Program);

Award ID: 2015CB554501

Custom metadata

ScienceOpen disciplines: Neurosciences

Keywords: inflammatory bowel disease,depression,tryptophan-kynurenine metabolic pathway,ido,the brain-gut axis

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ScienceOpen disciplines: Neurosciences

Keywords: inflammatory bowel disease, depression, tryptophan-kynurenine metabolic pathway, ido, the brain-gut axis

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

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Karger: Gastroenterology

Most cited references 142

Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease

The global burden of IBD: from 2015 to 2025.

Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism

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