Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease

PLoS Negl Trop Dis. 2013 Aug 15;7(8):e2381. doi: 10.1371/journal.pntd.0002381. eCollection 2013.

Abstract

Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT) were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA) metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / metabolism*
  • Child
  • Fatty Acids, Unsaturated / metabolism*
  • Female
  • Host-Parasite Interactions*
  • Humans
  • Leprosy / immunology*
  • Leprosy / pathology*
  • Male
  • Metabolome*
  • Middle Aged
  • Plasma / chemistry
  • Skin / chemistry
  • Skin / pathology
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Fatty Acids, Unsaturated

Grant support

This work was funded by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Canadian Institutes of Health Research, Genome British Columbia and Genome Canada. JJA was supported by a doctoral fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). LCMA was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research and an Atração de Jovens Talentos fellowship from the Ciência sem Fronteiras program of CNPq. CSdM received a fellowship from the Foundation for Scientific and Technological Development in Health, Fiocruz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.