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.