Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand.
Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
PLoS Negl Trop Dis. 2023 Feb 21;17(2):e0011119. doi: 10.1371/journal.pntd.0011119. eCollection 2023 Feb.
Trichinellosis, caused by a parasitic nematode of the genus Trichinella, is a zoonosis that affects people worldwide. After ingesting raw meat containing Trichinella spp. larvae, patients show signs of myalgia, headaches, and facial and periorbital edema, and severe cases may die from myocarditis and heart failure. The molecular mechanisms of trichinellosis are unclear, and the sensitivity of the diagnostic methods used for this disease are unsatisfactory. Metabolomics is an excellent tool for studying disease progression and biomarkers; however, it has never been applied to trichinellosis. We aimed to elucidate the impacts of Trichinella infection on the host body and identify potential biomarkers using metabolomics.
METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with T. spiralis larvae, and sera were collected before and 2, 4, and 8 weeks after infection. Metabolites in the sera were extracted and identified using untargeted mass spectrometry. Metabolomic data were annotated via the XCMS online platform and analyzed with Metaboanalyst version 5.0. A total of 10,221 metabolomic features were identified, and the levels of 566, 330, and 418 features were significantly changed at 2-, 4-, and 8-weeks post-infection, respectively. The altered metabolites were used for further pathway analysis and biomarker selection. A major pathway affected by Trichinella infection was glycerophospholipid metabolism, and glycerophospholipids comprised the main metabolite class identified. Receiver operating characteristic revealed 244 molecules with diagnostic power for trichinellosis, with phosphatidylserines (PS) being the primary lipid class. Some lipid molecules, e.g., PS (18:0/19:0)[U] and PA (O-16:0/21:0), were not present in metabolome databases of humans and mice, thus they may have been secreted by the parasites.
CONCLUSIONS/SIGNIFICANCE: Our study highlighted glycerophospholipid metabolism as the major pathway affected by trichinellosis, hence glycerophospholipid species are potential markers of trichinellosis. The findings of this study represent the initial steps in biomarker discovery that may benefit future trichinellosis diagnosis.
旋毛虫病是一种由旋毛形线虫属寄生虫引起的人畜共患寄生虫病，影响全球人类。患者在摄入含有旋毛虫幼虫的生肉后会出现肌肉痛、头痛、面部和眼眶周围水肿等症状，严重者可因心肌炎和心力衰竭而死亡。旋毛虫病的发病机制尚不清楚，且该疾病的诊断方法灵敏度也不高。代谢组学是研究疾病进展和生物标志物的一种极好工具，但尚未应用于旋毛虫病。我们旨在通过代谢组学阐明旋毛虫感染对宿主的影响并鉴定潜在的生物标志物。
方法/主要发现：本研究用旋毛虫幼虫感染小鼠，在感染前及感染后 2、4、8 周采集血清。使用非靶向质谱法提取和鉴定血清中的代谢物。代谢组学数据通过 XCMS 在线平台注释，并使用 Metaboanalyst 版本 5.0 进行分析。共鉴定出 10221 个代谢组学特征，感染后 2、4、8 周时分别有 566、330 和 418 个特征的水平发生显著变化。改变的代谢物用于进一步的通路分析和生物标志物选择。受旋毛虫感染影响的主要途径是甘油磷脂代谢，甘油磷脂是鉴定的主要代谢物类别。受试者工作特征揭示了 244 种具有旋毛虫病诊断能力的分子，其中磷脂酰丝氨酸（PS）是主要的脂质类别。一些脂质分子，如 PS（18:0/19:0）[U]和 PA（O-16:0/21:0），在人类和小鼠的代谢组数据库中不存在，因此它们可能是由寄生虫分泌的。
结论/意义：本研究强调了甘油磷脂代谢是旋毛虫病的主要影响途径，因此甘油磷脂种类可能是旋毛虫病的潜在标志物。本研究的结果代表了发现生物标志物的初步步骤，可能有助于未来的旋毛虫病诊断。
