4.5 Article

Chronic kidney disease, uremic milieu, and its effects on gut bacterial microbiota dysbiosis

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 315, Issue 3, Pages F487-F502

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00092.2018

Keywords

chronic kidney disease; gut bacterial microbiota; microbiology; urea transporters; uremic milieu

Funding

  1. National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) [UL1-TR-001412]
  2. University at Buffalo Genome, Environment and Microbiome
  3. Innovative Micro-Programs Accelerating Collaboration in Themes
  4. NIH [RO1-AI-125982, RO1-DE-024523]
  5. NIH
  6. NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001412] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI125982] Funding Source: NIH RePORTER
  8. NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE024523] Funding Source: NIH RePORTER

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Several lines of evidence suggest that gut bacterial microbiota is altered in patients with chronic kidney disease (CKD). though the mechanism of which this dysbiosis takes place is not well understood. Recent studies delineated changes in gut microbiota in both CKD patients and experimental animal models using microarray chips. We present 16S ribosomal RNA gene sequencing of both stool pellets and small bowel contents of C57BL/6J mice that underwent a remnant kidney model and establish that changes in microbiota take place in the early gastrointestinal tract. Increased intestinal urea concentration has been hypothesized as a leading contributor to dysbiotic changes in CKD. We show that urea transporters (UT)-A and UT-B mRNA are both expressed throughout the whole gastrointestinal tract. The noted increase in intestinal urea concentration appears to be independent of UTs' expression. Urea supplementation in drinking water resulted in alteration in bacterial gut microbiota that is quite different than that seen in CKD. This indicates that increased intestinal urea concentration might not fully explain the CKD- associated dysbiosis.

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