title: Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease.
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.
authors: Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Julio J
authors: JJ
authors: Amaral
authors: Luis Caetano M
authors: LC
authors: Antunes
authors: Cristiana S
authors: CS
authors: de Macedo
authors: Katherine A
authors: KA
authors: Mattos
authors: Jun
authors: J
authors: Han
authors: Jingxi
authors: J
authors: Pan
authors: André L P
authors: AL
authors: Candéa
authors: Maria das Graças M O
authors: Md
authors: Henriques
authors: Marcelo
authors: M
authors: Ribeiro-Alves
authors: Christoph H
authors: CH
authors: Borchers
authors: Euzenir N
authors: EN
authors: Sarno
authors: Patrícia T
authors: PT
authors: Bozza
authors: B Brett
authors: BB
authors: Finlay
authors: Maria Cristina V
authors: MC
authors: Pessolani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D002648:Child; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D007918:Leprosy / Q000276:immunology* / Q000473:pathology*; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D012867:Skin / Q000737:chemistry / Q000473:pathology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D005231:Fatty Acids, Unsaturated
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