Metabolic Homeostasis in Chronic Helminth Infection Is Sustained by Organ-Specific Metabolic Rewiring

Opisthorchiasis, is a hepatobiliary disease caused by flukes of the trematode family Opisthorchiidae. A chronic form of the disease implies a prolonged coexistence of a host and the parasite. The pathological changes inflicted by the worm to the host’s hepatobiliary system are well documented. Yet, the response to the infection also triggers a deep remodeling of the host systemic metabolism reaching a new homeostasis and affecting the organs beyond the worm location. Understanding the metabolic alternation in chronic opisthorchiasis, could help us to pinpoint pathways that underlie infection opening possibilities for the development of more selective treatment strategies. Here, with this report we apply an integrative, multicompartment metabolomics analysis, using multiple biofluids, stool samples and tissue extracts to describe metabolic changes in Opisthorchis felineus infected animals at the chronic stage. We show that the shift in lipid metabolism in the serum, a depletion of the amino acids pool, an alteration of the ketogenic pathways in the jejunum and a suppressed metabolic activity of the spleen are the key features of the metabolic host adaptation at the chronic stage of O. felineus infection. We describe this combination of the metabolic changes as a “metabolically mediated immunosuppressive status of organism” which develops during a chronic infection. This status in combination with other factors (e.g., parasite-derived immunomodulators) might increase risk of infection-related malignancy.后睾吸虫病（Opisthorchiasis）是由后睾科（Opisthorchiidae）吸虫纲吸虫引发的肝胆疾病。该疾病的慢性形式表现为宿主与寄生虫的长期共存。寄生虫对宿主肝胆系统造成的病理改变已有充分文献记载。然而，感染引发的宿主全身代谢深刻重塑可建立新的稳态，并影响寄生虫定植部位以外的器官。明确慢性后睾吸虫病的代谢变化特征，有助于精准定位感染相关的核心通路，为开发更具选择性的治疗策略提供可能。本研究采用整合式多室代谢组学（metabolomics）分析方法，结合多种生物体液、粪便样本及组织提取物，描述了慢性感染猫后睾吸虫（Opisthorchis felineus）的动物模型的代谢变化情况。研究结果显示，血清脂质代谢紊乱、氨基酸池耗竭、空肠生酮通路改变以及脾脏代谢活性受抑制，是猫后睾吸虫感染慢性期宿主代谢适应的关键特征。我们将这种慢性感染过程中形成的代谢变化组合定义为“代谢介导的机体免疫抑制状态”。该状态与其他因素（如寄生虫源性免疫调节因子）共同作用，可能增加感染相关恶性肿瘤的发病风险。