Plasma metabolomics in tuberculosis patients with and without concurrent type 2 diabetes at diagnosis and during antibiotic treatment

Sci Rep. 2019 Dec 10;9(1):18669. doi: 10.1038/s41598-019-54983-5.


Tuberculosis (TB) and type 2 diabetes mellitus (DM), a major TB risk factor, are both accompanied by marked alterations in metabolic processes. Dissecting the specific metabolic changes induced by disease through metabolomics has shown potential to improve our understanding of relevant pathophysiological mechanisms of disease, which could lead to improved treatment. Targeted tandem liquid chromatography-mass spectrometry (LC-MS/MS) was used to compare amine and acylcarnitine levels in plasma samples of patients with TB or TB-DM from Indonesia at time of diagnosis and during antibiotic treatment. Partial least squares discrimination analysis (PLS-DA) showed good separation of patient groups. Amine levels were strongly altered in both disease groups compared to healthy controls, including low concentrations of citrulline and ornithine. Several amino acid ratios discriminated TB from controls (phenylalanine/histidine; citrulline/arginine; kynurenine/tryptophan), possibly reflecting changes in indoleamine-pyrrole 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) activity. Choline, glycine, serine, threonine and homoserine levels were lower in TB-DM compared to TB, and, in contrast to other analytes, did not normalize to healthy control levels during antibiotic treatment. Our results not only provide important validation of previous studies but also identify novel biomarkers, and significantly enhance our understanding of metabolic changes in human TB and TB-DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amines / blood
  • Anti-Bacterial Agents / therapeutic use*
  • Blood Proteins / drug effects*
  • Blood Proteins / metabolism
  • Body Weight
  • Carnitine / analogs & derivatives
  • Carnitine / blood
  • Chromatography, Liquid
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Female
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Indonesia
  • Least-Squares Analysis
  • Male
  • Metabolomics
  • Middle Aged
  • Nitric Oxide Synthase / metabolism
  • Principal Component Analysis
  • ROC Curve
  • Tandem Mass Spectrometry
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / drug therapy*
  • Young Adult


  • Amines
  • Anti-Bacterial Agents
  • Blood Proteins
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • acylcarnitine
  • Nitric Oxide Synthase
  • Carnitine