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Tryptophan catabolism reflects disease activity in human tuberculosis
Jeffrey M. Collins, … , Henry M. Blumberg, Thomas R. Ziegler
Jeffrey M. Collins, … , Henry M. Blumberg, Thomas R. Ziegler
Published May 5, 2020
Citation Information: JCI Insight. 2020;5(10):e137131. https://doi.org/10.1172/jci.insight.137131.
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Research Article Infectious disease Metabolism

Tryptophan catabolism reflects disease activity in human tuberculosis

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Abstract

There is limited understanding of the role of host metabolism in the pathophysiology of human tuberculosis (TB). Using high-resolution metabolomics with an unbiased approach to metabolic pathway analysis, we discovered that the tryptophan pathway is highly regulated throughout the spectrum of TB infection and disease. This regulation is characterized by increased catabolism of tryptophan to kynurenine, which was evident not only in active TB disease but also in latent TB infection (LTBI). Further, we found that tryptophan catabolism is reversed with effective treatment of both active TB disease and LTBI in a manner commensurate with bacterial clearance. Persons with active TB and LTBI also exhibited increased expression of indoleamine 2,3-dioxygenase-1 (IDO-1), suggesting IDO-1 mediates observed increases in tryptophan catabolism. Together, these data indicate IDO-1–mediated tryptophan catabolism is highly preserved in the human response to Mycobacterium tuberculosis and could be a target for biomarker development as well as host-directed therapies.

Authors

Jeffrey M. Collins, Amnah Siddiqa, Dean P. Jones, Ken Liu, Russell R. Kempker, Azhar Nizam, N. Sarita Shah, Nazir Ismail, Samuel G. Ouma, Nestani Tukvadze, Shuzhao Li, Cheryl L. Day, Jyothi Rengarajan, James C.M. Brust, Neel R. Gandhi, Joel D. Ernst, Henry M. Blumberg, Thomas R. Ziegler

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Figure 1

The tryptophan metabolic pathway is highly regulated in the host response to TB disease and chemotherapy-mediated bacterial clearance.

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The tryptophan metabolic pathway is highly regulated in the host respons...
(A) Differences in metabolic pathway activity (21) in persons from the country of Georgia with active TB disease at the time of diagnosis (n = 89) versus controls without active TB disease (n = 57). (B) Changes in metabolic pathway activity in persons from Georgia over 4 months of treatment for drug-susceptible TB (DS-TB) disease with directly observed therapy. The horizontal bars show the magnitude of the –log(P value) for pathway enrichment in each pathway.

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