Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
PLoS Negl Trop Dis. 2013 Aug 15;7(8):e2381. doi: 10.1371/journal.pntd.0002381. eCollection 2013.
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.
尽管在过去几十年中付出了相当大的努力，但我们对麻风病发病机制的理解仍然有限。病原体和宿主之间的复杂相互作用对宿主代谢有深远的影响。为了探索与麻风病相关的代谢紊乱，我们分析了麻风病患者的血清代谢组。在多药治疗（MDT）结束前后收集的瘤型和结核样患者的样本进行了高通量代谢谱分析。我们的结果表明，在麻风病期间存在明显的代谢改变，在 MDT 结束时会减轻。表现出最高调节的途径与多不饱和脂肪酸（PUFA）代谢有关，重点是抗炎、促解决的 omega-3 脂肪酸。这些结果通过酶联免疫吸附测定法进行的类二十烷酸测量得到了证实。与血清中改变的代谢物谱相吻合，皮肤标本的代谢组学分析显示来自脂肪酶活性的脂质水平发生了变化，包括 PUFAs，表明高度感染病变中的脂质周转率很高。我们的数据表明，omega-6 和 omega-3、源自 PUFA 的促解决的脂质介质有助于减少组织损伤，而与麻风病疾病期间的病原体负担无关。我们的结果表明，综合代谢组学方法可用于识别疾病病理学的潜在贡献者，这可能有助于为麻风病和其他炎症性疾病开发更有针对性的治疗方法。
