title: Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients.
abstract: Although tuberculosis (TB) causes more deaths than any other pathogen, most infected individuals harbor the pathogen without signs of disease. We explored the metabolome of >400 small molecules in serum of uninfected individuals, latently infected healthy individuals and patients with active TB. We identified changes in amino acid, lipid and nucleotide metabolism pathways, providing evidence for anti-inflammatory metabolomic changes in TB. Metabolic profiles indicate increased activity of indoleamine 2,3 dioxygenase 1 (IDO1), decreased phospholipase activity, increased abundance of adenosine metabolism products, as well as indicators of fibrotic lesions in active disease as compared to latent infection. Consistent with our predictions, we experimentally demonstrate TB-induced IDO1 activity. Furthermore, we demonstrate a link between metabolic profiles and cytokine signaling. Finally, we show that 20 metabolites are sufficient for robust discrimination of TB patients from healthy individuals. Our results provide specific insights into the biology of TB and pave the way for the rational development of metabolic biomarkers for TB.
authors: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany. january.weiner@mpiib-berlin.mpg.de
authors: January
authors: J
authors: Weiner
authors: Shreemanta K
authors: SK
authors: Parida
authors: Jeroen
authors: J
authors: Maertzdorf
authors: Gillian F
authors: GF
authors: Black
authors: Dirk
authors: D
authors: Repsilber
authors: Anna
authors: A
authors: Telaar
authors: Robert P
authors: RP
authors: Mohney
authors: Cordelia
authors: C
authors: Arndt-Sullivan
authors: Christian A
authors: CA
authors: Ganoza
authors: Kellen C
authors: KC
authors: Faé
authors: Gerhard
authors: G
authors: Walzl
authors: Stefan H E
authors: SH
authors: Kaufmann
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007737:Kynurenine / Q000096:biosynthesis; D008297:Male; D055432:Metabolomics; D013312:Stress, Physiological; D014397:Tuberculosis, Pulmonary / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine