Hu Xiaofang, Xie Yuhong, Xiao Yi, Zeng Wenjing, Gong Zhicheng, Du Jie
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; The Hunan Institute of Pharmacy Practice and Clinical Research, Changsha, 410008, Hunan, China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; The Hunan Institute of Pharmacy Practice and Clinical Research, Changsha, 410008, Hunan, China.
Eur J Pharmacol. 2020 Nov 5;886:173555. doi: 10.1016/j.ejphar.2020.173555. Epub 2020 Sep 14.
Renal fibrosis is a major pathological process in the progression of various chronic kidney diseases to end-stage renal disease (ESRD). Growing evidence has suggested that gut microbiota dysbiosis is closely related to ESRD. However, the interplay between altered fecal microbiome and metabolome during the renal fibrotic process remains unclear. Herein, an integrated approach of 16S ribosomal DNA sequencing combined with an ultra-high performance liquid chromatography-mass spectrometry-based metabolomics platform was applied to investigate the dynamic changes of fecal microbiota and metabolites throughout renal fibrosis progression in a mouse model of unilateral ureteral obstruction (UUO). The composition of gut microbiota changed markedly before and after UUO surgery. UUO mice showed a decrease in short-chain fatty acids-producing genera, including Bacteroides, Prevotellaceae_UCG-001, Roseburia, and Lachnospiraceae_NK4A136_group, as well as an increase in the genera Parasutterella and Alistipes, which changed dynamically over time. Additionally, 41 differential metabolites, mainly involved in 12 metabolic pathways, including inositol phosphate metabolism, primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, taurine and hypotaurine metabolism, purine metabolism, were identified in the UUO mice before and after surgery. Four fecal metabolites, myo-inositol, dodecanoic acid, N-acetylputrescine, and anthranilic acid, were positively associated with the progression of renal fibrosis. Moreover, by using multi-omics analyses, we found the alteration in UUO-related gut microbiota was correlated with a change in fecal metabolites. Therefore, our results provide insights into disturbances of the microbiome-metabolome interface in the progression of UUO-related renal fibrosis.
肾纤维化是各种慢性肾脏病进展至终末期肾病（ESRD）的主要病理过程。越来越多的证据表明，肠道微生物群失调与ESRD密切相关。然而，在肾纤维化过程中，粪便微生物组与代谢组之间的相互作用仍不清楚。在此，我们应用16S核糖体DNA测序与基于超高效液相色谱-质谱联用的代谢组学平台相结合的综合方法，研究单侧输尿管梗阻（UUO）小鼠模型在肾纤维化进展过程中粪便微生物群和代谢物的动态变化。UUO手术前后肠道微生物群的组成发生了显著变化。UUO小鼠中产生短链脂肪酸的菌属减少，包括拟杆菌属、普雷沃氏菌科_UCG-001、罗斯氏菌属和毛螺菌科_NK4A136_组，而副萨特氏菌属和阿利斯氏菌属增加，且随时间动态变化。此外，在UUO小鼠手术前后鉴定出41种差异代谢物，主要涉及12条代谢途径，包括肌醇磷酸代谢、初级胆汁酸生物合成、不饱和脂肪酸生物合成、牛磺酸和亚牛磺酸代谢、嘌呤代谢。四种粪便代谢物，即肌醇、十二烷酸、N-乙酰腐胺和邻氨基苯甲酸，与肾纤维化的进展呈正相关。此外，通过多组学分析，我们发现与UUO相关的肠道微生物群的改变与粪便代谢物的变化相关。因此，我们的结果为UUO相关肾纤维化进展过程中微生物组-代谢组界面的紊乱提供了见解。
