Haonon Ornuma, Liu Zhigang, Dangtakot Rungtiwa, Intuyod Kitti, Pinlaor Porntip, Puapairoj Anucha, Cha'on Ubon, Sengthong Chatchawan, Pongking Thatsanapong, Onsurathum Sudarat, Yingklang Manachai, Phetcharaburanin Jutarop, Li Jia V, Pinlaor Somchai
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
J Proteome Res. 2021 Aug 6;20(8):3940-3951. doi: 10.1021/acs.jproteome.1c00246. Epub 2021 Jul 16.
(Ov) infection causes hepatobiliary diseases and is a major risk factor for cholangiocarcinoma. While several omics approaches have been employed to understand the pathogenesis of opisthorchiasis, effects of Ov infection on the host systemic metabolism and fecal microbiota have not been fully explored. Here, we used a H NMR spectroscopy-based metabolic phenotyping approach to investigate Ov infection-induced metabolic disturbances at both the acute (1 month postinfection, 1 mpi) and chronic (4 mpi) stages in hamsters. A total of 22, 3, and 4 metabolites were found to be significantly different in the liver, serum, and urine, respectively, between Ov+ and Ov- groups. Elevated levels of hepatic amino acids and tricarboxylic acid (TCA)-cycle intermediates (fumarate and malate) were co-observed with liver injury in acute infection, whereas fibrosis-associated metabolites (e.g., glycine and glutamate) increased at the chronic infection stage. Lower levels of lipid signals ((C) and CCHCO) and higher levels of lysine and -inositol were observed in serum from Ov+ hamsters at 1 mpi compared to Ov- controls. Urinary levels of phenylacetylglycine (a host-bacterial cometabolite) and tauro-β-muricholic acid were higher in the Ov+ group, which coexisted with hepatic and mild kidney fibrosis. Furthermore, Ov+ animals showed higher relative abundances of fecal (Archaea), , and compared to the noninfected controls. In conclusion, along with liver and kidney pathologies, infection resulted in hepatic and mild renal pathologies, disturbed hepatic amino acid metabolism and the TCA cycle, and induced changes in the fecal microbial composition and urinary host-microbial cometabolism. This study provides the initial step toward an understanding of local and systemic metabolic responses of the host to infection.
华支睾吸虫（Ov）感染会引发肝胆疾病，是胆管癌的主要风险因素。尽管已采用多种组学方法来了解华支睾吸虫病的发病机制，但Ov感染对宿主全身代谢和粪便微生物群的影响尚未得到充分研究。在此，我们使用基于核磁共振氢谱的代谢表型分析方法，研究Ov感染在仓鼠急性（感染后1个月，1mpi）和慢性（4mpi）阶段引起的代谢紊乱。结果发现，Ov+组和Ov-组之间，肝脏、血清和尿液中分别有22种、3种和4种代谢物存在显著差异。急性感染时，肝脏氨基酸和三羧酸（TCA）循环中间体（富马酸和苹果酸）水平升高，同时伴有肝损伤；而在慢性感染阶段，与纤维化相关的代谢物（如甘氨酸和谷氨酸）增加。与Ov-对照组相比，1mpi时Ov+仓鼠血清中的脂质信号（（C）和CCHCO）水平较低，赖氨酸和肌醇水平较高。Ov+组尿中苯乙酰甘氨酸（一种宿主-细菌共代谢物）和牛磺-β-鼠胆酸水平较高，同时伴有肝脏和轻度肾脏纤维化。此外，与未感染的对照组相比，Ov+动物粪便中的古菌、和的相对丰度更高。总之，除肝脏和肾脏病变外，Ov感染还导致肝脏和轻度肾脏病变、肝脏氨基酸代谢和TCA循环紊乱，并引起粪便微生物组成和尿液宿主-微生物共代谢的变化。本研究为了解宿主对Ov感染的局部和全身代谢反应迈出了第一步。
