High-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults Across the Leprosy Spectrum

High-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults Across the Leprosy Spectrum

Abstract Background High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabol...

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Bibliographic Details
Published in:The Journal of infectious diseases Vol. 229; no. 4; pp. 1189 - 1199
Main Authors: Fairley, Jessica K, Ferreira, José A, Fraga, Lucia A O, Lyon, Sandra, Valadão Cardoso, Thales M, Boson, Victor Campos, Madureira Nunes, Ana Carolina, Medeiros Cinha, Eloisa H, de Oliveira, Lorena B P, Magueta Silva, Erica B, Marçal, Pedro H F, Branco, Alexandre C, Grossi, Maria Aparecida F, Jones, Dean P, Ziegler, Thomas R, Collins, Jeffrey M
Format: Journal Article
Language:English
Published: US Oxford University Press 12-04-2024
Subjects:
Carnitine
Energy metabolism
Fatty acids
Infectious diseases
Informatics
Leprosy
Leukotrienes
Major
Metabolic pathways
Metabolism
Metabolites
Metabolomics
Prostaglandins
Tryptophan
Vitamin A
Vitamin D3
leprosy
retinol
high-resolution metabolomics
nutrition
fatty acids
vitamin D
carnitine
metabolism
energy metabolism
tryptophan
Hansen's disease
Mycobacterium leprae
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Summary:Abstract Background High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism. Methods From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass, mass to charge ratio m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared. Results Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (P < .05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism, between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (P < .05). Discussion Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB versus PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease. Results of our untargeted high-resolution metabolomics study demonstrated differentially regulated metabolic pathways that differed significantly across cases of leprosy and controls with vitamin D, retinol, and fatty acid metabolites featuring prominently, supporting potential roles in the immune response to infection.
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Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiad410