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Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression

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posted on 2023-05-19, 03:17 authored by Lim, CK, Bilgin, A, Lovejoy, DB, Tan, V, Bustamante, S, Bruce TaylorBruce Taylor, Bessede, A, Brew, BJ, Guillemin, GJ
Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers.

History

Publication title

Scientific Reports

Volume

7

Article number

41473

Number

41473

Pagination

1-9

ISSN

2045-2322

Department/School

Menzies Institute for Medical Research

Publisher

Nature Publishing Group

Place of publication

United Kingdom

Rights statement

© The Author(s) 2017 Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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