Summary of project PR001809

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001809. The data can be accessed directly via it's Project DOI: 10.21228/M8W71R This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001809
Project DOI:doi: 10.21228/M8W71R
Project Title:Plasma metabolomics reveals distinct biological and diagnostic signatures for melioidosis
Project Summary:Rationale: The global burden of sepsis is greatest in low-resource settings. Melioidosis, infection with the Gram-negative bacterium Burkholderia pseudomallei, is a frequent cause of fatal sepsis in endemic tropical regions such as Southeast Asia. Objectives: To investigate whether plasma metabolomics would identify biological pathways specific to melioidosis and yield clinically meaningful biomarkers. Methods: Using a comprehensive approach, differential enrichment of plasma metabolites and pathways was systematically evaluated in individuals selected from a prospective cohort of patients hospitalized in rural Thailand with infection. Statistical and bioinformatics methods were used to distinguish metabolomic features and processes specific to melioidosis patients, and between fatal and non-fatal cases. Measurements and Main Results: Metabolomic profiling and pathway enrichment analysis of plasma samples of melioidosis (n=175) and non-melioidosis infections (n=75) revealed a distinct immuno-metabolic state among patients with melioidosis, as suggested by excessive tryptophan catabolism in the kynurenine pathway and significantly increased levels of sphingomyelins and ceramide species. We derived a 12-metabolite classifier to distinguish melioidosis from other infections, yielding an area under the receiver operating characteristic curve of 0.87 in a second validation set of patients. Melioidosis non-survivors (n=94) had a significantly disturbed metabolome compared to survivors (n=81) with increased leucine, isoleucine and valine metabolism, and elevated circulating free fatty acids and acylcarnitines. A limited 8-metabolite panel showed promise as an early prognosticator of mortality in melioidosis. Conclusions: Melioidosis induces a distinct metabolomic state that can be examined to distinguish underlying pathophysiological mechanisms associated with death. A twelve-metabolite signature accurately differentiates melioidosis from other infections and may have diagnostic applications.
Institute:University of Washington
Last Name:Gharib
First Name:Sina
Address:Center for Lung Biology, 850 Republican St, Seattle WA 98109
Funding Source:NIH (R01HL113382, R01AI137111, R01GM114029, R21AI173435) and the Wellcome Trust (090219/Z/09/Z, 101103/Z/13/Z)
Contributors:Lu Xia, T. Eoin West

Summary of all studies in project PR001809

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002909 Plasma metabolomics reveals distinct biological and diagnostic signatures for melioidosis Homo sapiens University of Washington MS 2023-10-17 1 300 Uploaded data (1.3M)