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Longitudinal analysis of fecal microbiome and metabolome during renal fibrotic progression in a unilateral ureteral obstruction animal model

Xiaofang Hu, Yuhong Xie, Yi Xiao, Wenjing Zeng, Z. Gong, Jie Du

European Journal of Pharmacology, 2020

25 citations

Abstract

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…

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