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Microbiome–metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease

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Abstract

Dysbiosis of the gut microbiome and related metabolites in chronic kidney disease (CKD) have been intimately associated with the prevalence of cardiovascular diseases. Unfortunately, thus far, there is a paucity of sufficient knowledge of gut microbiome and related metabolites on CKD progression partly due to the severely limited investigations. Using a 5/6 nephrectomized (NX) rat model, we carried out 16S rRNA sequence and untargeted metabolomic analyses to explore the relationship between colon’s microbiota and serum metabolites. Marked decline in microbial diversity and richness was accompanied by significant changes in 291 serum metabolites, which were mediated by altered enzymatic activities and dysregulations of lipids, amino acids, bile acids and polyamines metabolisms. Interestingly, CCr was directly associated with some microbial genera and polyamine metabolism. However, SBP was directly related to certain microbial genera and glycine-conjugated metabolites in CKD rats. Administration of poricoic acid A (PAA) and Poria cocos (PC) ameliorated microbial dysbiosis as well as attenuated hypertension and renal fibrosis. In addition, treatments with PAA and PC lowered serum levels of microbial-derived products including glycine-conjugated compounds and polyamine metabolites. Collectively, the present study confirmed the CKD-associated gut microbial dysbiosis and identified a novel dietary and therapeutic strategy to improve the gut microbial dysbiosis and the associated metabolomic disorders and retarded the progression of kidney disease in the rat model of CKD.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (nos. 81872985, 81673578, 81603271).

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  1. Ya-Long Feng, Gang Cao and Dan-Qian Chen contributed equally as co-first authors to this work.

Authors and Affiliations

  1. School of Pharmacy, Faculty of Life Science & Medicine, Northwest University, No. 229 Taibai North Road, Xi’an, Shaanxi, 710069, China

    Ya-Long Feng, Dan-Qian Chen, Lin Chen, Jun Zhang, Ming Wang & Ying-Yong Zhao

  2. Division of Nephrology and Hypertension, School of Medicine, University of California Irvine, Irvine, CA, 92897, USA

    Nosratola D. Vaziri

  3. School of Pharmacy, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, Zhejiang, 310053, China

    Gang Cao

  4. Department of Internal Medicine, Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, 87131, USA

    Yan Guo

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  1. Ya-Long Feng
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Feng, YL., Cao, G., Chen, DQ. et al. Microbiome–metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease. Cell. Mol. Life Sci. 76, 4961–4978 (2019). https://doi.org/10.1007/s00018-019-03155-9

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