Integrative metagenomic and metabolomic analyses reveal severity-specific signatures of gut microbiota in chronic kidney disease

I. Wen Wu, Sheng Siang Gao, Hsin Cheng Chou, Huang Yu Yang, Lun Ching Chang, Yu Lun Kuo, Michael Cong Vinh Dinh, Wen-Hung Chung, Chi Wei Yang, Hsin Chih Lai, Wen Ping Hsieh, Shih Chi Su

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

Chronic kidney disease (CKD) is a serious healthcare dilemma, associated with specific changes in gut microbiota and circulating metabolome. Yet, the functional capacity of CKD microbiome and its intricate relationship with the host metabolism at different stages of disease are less understood. Methods: Here, shotgun sequencing of fecal samples and targeted metabolomics profiling of serum bile acids, short- and medium-chain fatty acids, and uremic solutes were performed in a cohort of CKD patients with different severities and non-CKD controls. Results: We identified that levels of 13 microbial species and 6 circulating metabolites were significantly altered across early to advanced stages or only in particular stage(s). Among these, Prevotella sp. 885 (decreased) was associated with urea excretion, while caproic acid (decreased) and p-cresyl sulfate (elevated) were positively and negatively correlated with the glomerular filtration rate, respectively. In addition, we identified gut microbial species linked to changes in circulating metabolites. Microbial genes related to secondary bile acid biosynthesis were differentially abundant at the early stage, while pathway modules related to lipid metabolism and lipopolysaccharide biosynthesis were enriched in the CKD microbiome at the advanced stage, suggesting that changes in microbial metabolism and host inflammation may contribute to renal health. Further, we identified metagenomic and metabolomic markers to discriminate cases of different severities from the controls, among which Bacteroides eggerthii individually was of particular value in early diagnosis. Conclusions: Our dual-omics data reveal the connections between intestinal microbes and circulating metabolites perturbed in CKD, which may be of etiological and diagnostic importance.

Original languageEnglish
Pages (from-to)5398-5411
Number of pages14
JournalTheranostics
Volume10
Issue number12
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • Chronic kidney disease
  • Gut microbiome
  • Serum metabolites
  • Short-chain fatty acid
  • Uremic solute

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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