02678nas a2200433 4500000000100000008004100001260001200042653002300054653002500077653001400102653002200116653001600138653003300154653001200187653001500199653001400214653001200228653001500240653001400255100001400269700001500283700001200298700001100310700001400321700001200335700001200347700001200359700001800371700001400389700001400403700001300417700001300430700001200443700001400455700001400469245015400483520159300637022001402230 2023 d c09/202310aHansen’s disease10aMycobacterium leprae10acarnitine10aEnergy Metabolism10aFatty Acids10ahigh resolution metabolomics10aleprosy10aMetabolism10aNutrition10aretinol10aTryptophan10aVitamin D1 aFairley J1 aFerreira J1 aFraga L1 aLyon S1 aCardoso T1 aBoson V1 aNunes A1 aCinha E1 ade Oliveira L1 aMagueta E1 aMarçal P1 aBranco A1 aGrossi M1 aJones D1 aZiegler T1 aCollins J00aHigh-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults across the Leprosy Spectrum.3 a

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 2018-2019, 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 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<0.05) 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<0.05).

Discussion: Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB vs PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease.

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