Full project title:
Using plasma metabolomics to increase our understanding of metabolic changes in leprosy and associated reactions: A proof-of-concept study.
Project Coordination
Emory University School of Medicine, USA
Partner
Faculdade da Saúde e Ecologia Humana (FASEH), Brazil
Aim: There are many knowledge gaps surrounding leprosy transmission, diagnostics and morbidity management. This research project studied the interaction between the host (humans) and the pathogen (Mycobacterium leprae) by looking for “metabolic signatures” using innovative methods.
Final project summary:
High resolution metabolomics (HRM) has led to better understanding of host-pathogen interactions of many infectious diseases but has rarely been used in studies of metabolism in leprosy. Thousands of small molecules can be detected through HRM and advanced data extraction. Our objectives were to identify unique metabolic signatures related to leprosy presentation and to explore possible links between nutrients, host metabolism and disease manifestations. Between June 2018 and December 2019, adults newly diagnosed with leprosy and healthy controls were recruited from leprosy referral clinics in Minas Gerais, Brazil. Plasma samples were analyzed at the Clinical Biomarkers Laboratory at Emory University, Atlanta GA. Metabolites were detected using an established HRM workflow and characterized by accurate mass m/z and retention time. The mummichog informatics package was used to compare metabolic pathway activity between groups. Additionally, select individual metabolites were quantified and compared. Analyses was controlled for age and sex of study participants. Forty-two individuals with leprosy were enrolled, of which 26 (62%) were multibacillary (MB) and 16 (38%) werepaucibacillary (PB). Persons with leprosy were compared to 25 asymptomatic controls (9 community controls and 16 household contacts). We found statistically significant differences in arachidonic acid and prostaglandin metabolism as well as differences in vitamin D, retinol, carnitine shuttle, and tryptophan metabolism. Our findings suggest interdependency of these pathways at the intersection of metabolismand immunity and strongly support further investigations of these metabolic signatures that can greatly increase our understanding of the underlying pathophysiology of leprosy. However, the in vivo, real world data that plasma HRM can provide is critical to compliment the invitro mechanistic studies. As described, many of these pathways are highly interdependent and the output provides further avenues of research both within HRM as well as other methods.
In summary, this study described many metabolic differences across healthy controls, MB leprosy and PB leprosy especially in regards to fatty acids, energy metabolism, micronutrients, and tryptophan metabolism. These findings indicate that future studies investigating the intersection of host metabolism and the immune response to M. leprae are warranted. Furthermore, understanding metabolic differencesin persons with leprosy and asymptomatic persons with evidence of prior exposure would enhance our ability to understand the pathophysiology of disease and identify biomarkers that differentiate “active” and “latent” disease. Further prospective well-controlled and well-powered studies using HRM in individuals susceptible to leprosy, may be useful to identify metabolites or metabolic profiles that could eventually be adapted as plasma biomarkers of leprosy and predict progression of this ancient disease. In a disease with anunculturable pathogen and long incubation period, HRM clearly shows a path to better understanding of the disease that will advanceearlier diagnosis, prevention, and treatment.
Impact
High-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults across the Leprosy Spectrum. Fairley J, Ferreira J, Fraga L, et al. The Journal of infectious diseases. 2023;
ASTMH 2021 annualmeeting: oralpresentation: High resolutionmetabolomics highlightdifferences in lipid andnutritional metabolismacross the leprosyspectrum providingavenue for advances inleprosy host-pathogenresearch; Jessica K.Fairley, José A. Ferreira,Thomas R. Ziegler, DeanP. Jones, Lucia A. Fraga,Sandra Lyon, Jeffrey M.Collins