Key Laboratory of Hydraulic and Waterway Engineering of the Ministry of Education, School of River and Ocean Engineering, Chongqing Jiaotong University, Chongqing 400074, China; Chongqing Institute of Green and Intelligent Technology, Chongqing School of University of Chinese Academy of Sciences, Chinese Academy of Sciences, Chongqing, 400714, China.
School of Public Health, Chongqing Medical University, Chongqing, 400016, China.
Environ Pollut. 2023 Nov 15;337:122524. doi: 10.1016/j.envpol.2023.122524. Epub 2023 Sep 6.
Chronic kidney disease of unknown etiology (CKDu) is an endemic disease in the dry zone of farming communities, Sri Lanka. The drinking water in a CKDu prevalent area contains a high concentration of F, hardness and other environmental pollutants, including heavy metals and microcystin, which are considered possible etiology of CKDu in these areas. Here, multi-omics data with host transcriptome, metabolome and gut microbiomes were obtained using simulated local drinking water of Sri Lanka after their exposure to adult zebrafish. Based on an integrated multi-omics analysis in the context of host physiology in the kidney injury samples with different pathologic grades, two common pathways necroptosis and purine metabolism were identified as potentially important pathways that affect kidney injury. The key metabolite acetyl adenylate in the purine metabolism pathway was significantly positively correlated with Comamonas (rho = 0.72) and significantly negatively correlated with Plesiomonas (rho = -0.58). This crucial metabolite and two key gut bacteria genera may not only be potential markers but also potential therapeutic targets in the uric acid metabolic pathway, which is an important factor in the pathogenesis of acute kidney injury (AKI) in general, as well as of chronic kidney disease (CKD). Based on this, we revealed the urea metabolism pathway of kidney injury in zebrafish and provided a new avenue for the treatment of CKDu in Sri Lanka.
原因不明的慢性肾病（CKDu）是斯里兰卡干旱地区农耕社区的地方病。CKDu 流行地区的饮用水含有高浓度的氟、硬度和其他环境污染物，包括重金属和微囊藻毒素，这些被认为是这些地区 CKDu 的可能病因。在这里，使用模拟的当地饮用水对成年斑马鱼进行暴露后，获得了宿主转录组、代谢组和肠道微生物组的多组学数据。基于不同病理分级的肾脏损伤样本中宿主生理学的综合多组学分析，鉴定出两个常见的途径：坏死性凋亡和嘌呤代谢，这两个途径可能是影响肾脏损伤的重要途径。嘌呤代谢途径中的关键代谢物乙酰腺嘌呤与 Comamonas（rho=0.72）呈显著正相关，与 Plesiomonas（rho=-0.58）呈显著负相关。这种关键代谢物和两种关键肠道细菌属不仅可能是潜在的标志物，而且可能是尿酸代谢途径的潜在治疗靶点，尿酸代谢途径是急性肾损伤（AKI）以及慢性肾病（CKD）发病机制中的一个重要因素。基于这一点，我们揭示了斑马鱼肾脏损伤的尿素代谢途径，并为治疗斯里兰卡的 CKDu 提供了新的途径。
