School of Public Health, Chongqing Medical University, Chongqing, 400016, China.
Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China; Department of Geology, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka.
Environ Pollut. 2023 Sep 1;332:121967. doi: 10.1016/j.envpol.2023.121967. Epub 2023 Jun 6.
Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, K-ATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H&E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas, Paracoccus, and ZOR0006, etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on "bio-markers" as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu.
斯里兰卡病因不明的慢性肾病（CKDu）作为一个全球健康问题引起了广泛关注。然而，当地饮用水中的环境因素如何导致生物体的肾脏损伤仍不得而知。我们研究了多种环境因素，包括水硬度和氟化物（HF）、重金属（HM）、微囊藻毒素-LR（MC-LR）及其联合暴露（HFMM），以阐明它们对斑马鱼 CKDu 风险的毒性作用。急性暴露会影响肾脏发育并抑制 Na，K-ATPase alpha1A4：GFP 斑马鱼肾脏的荧光。慢性暴露会影响成年雌雄鱼的体重，并通过组织病理学分析诱导肾脏损伤。此外，暴露还显著扰乱了肠道微生物群的差异表达基因（DEGs）、多样性和丰富度，以及与肾脏功能相关的关键代谢物。转录组分析表明，与肾脏相关的 DEGs 与肾细胞癌、近端肾小管重吸收碳酸氢盐、钙信号通路和 HIF-1 信号通路有关。显著失调的肠道微生物群与环境因素和 H&E 评分密切相关，这表明了肾脏风险的机制。值得注意的是，Spearman 相关分析表明，变化的细菌如假单胞菌、副球菌和 ZOR0006 等与 DEGs 和代谢物有显著关联。因此，对多种环境因素的评估为潜在的靶向信号通路、代谢物和肠道细菌的“生物标志物”作为监测或保护居民免受 CKDu 的治疗方法提供了新的见解。
