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

  • Ya-Long Feng
  • Gang Cao
  • Dan-Qian Chen
  • Nosratola D. Vaziri
  • Lin Chen
  • Jun Zhang
  • Ming Wang
  • Yan Guo
  • Ying-Yong ZhaoEmail author
Original Article

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.

Keywords

Renal fibrosis Gut microbiota Metabolome Hypertension Creatinine clearance rate Polyamine metabolism 

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

18_2019_3155_MOESM1_ESM.docx (1.8 mb)
Supplementary material 1 (DOCX 1872 kb)
18_2019_3155_MOESM2_ESM.docx (386 kb)
Supplementary material 2 (DOCX 386 kb)

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Authors and Affiliations

  1. 1.School of Pharmacy, Faculty of Life Science & MedicineNorthwest UniversityXi’anChina
  2. 2.Division of Nephrology and Hypertension, School of MedicineUniversity of California IrvineIrvineUSA
  3. 3.School of PharmacyZhejiang Chinese Medical UniversityHangzhouChina
  4. 4.Department of Internal Medicine, Comprehensive Cancer CenterUniversity of New MexicoAlbuquerqueUSA

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