Gut microbiota as diagnostic tools for mirroring disease progression and circulating nephrotoxin levels in chronic kidney disease: Discovery and validation study

I. Wen Wu, Chan Yu Lin, Lun Ching Chang, Chin Chan Lee, Chih Yung Chiu, Heng Jung Hsu, Chiao Yin Sun, Yuen Chan Chen, Yu Lun Kuo, Chi Wei Yang, Sheng Siang Gao, Wen Ping Hsieh, Wen Hung Chung, Hsin Chih Lai, Shih Chi Su

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

Abstract

The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in large human cohort. Significant compositional and functional differences in the intestinal microbiota (by 16S rRNA gene sequencing) were noted among 30 controls and 92 (31 mild, 30 moderate and 31 advanced) patients at different chronic kidney disease (CKD) stages (discovery cohort). A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at early-stage of disease. The performance was further confirmed in a validation cohort comprising 22 controls and 76 peritoneal dialysis patients. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified. Prediction of the functional capabilities of microbial communities showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages. Collectively, our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of chronic kidney disease and highlight a usefulness of specific gut microorganisms as possible disease differentiate marker of this global health burden.

Original languageEnglish
Pages (from-to)420-434
Number of pages15
JournalInternational Journal of Biological Sciences
Volume16
Issue number3
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • Chronic kidney disease
  • Gut microbiome
  • Indoxyl sulfate
  • P-cresyl sulfate

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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