Chronic kidney disease (CKD) may alter the homeostatic relationship between human hosts and their intestinal tract microbial inhabitants (i.e., the gut microbiota) due to the enhanced delivery of urea to the gut microbiota, alterations in diet, and the decrease in urinary excretion of small molecules produced by the gut microbiota. As a result, both the composition of the gut microbiota and its metabolite byproducts may be altered in patients with CKD. We propose a set of inter-related specific aims to examine the association between CKD, gut microbiota and the fecal metabolome, the plasma metabolome, and the development of clinical outcomes using a longitudinal prospective cohort within the Chronic Renal Insufficiency Cohort (CRIC) Study. In addition, we propose a small interventional study to eradicate and then re-populate the gut microbiota among an additional population of CKD patients to identify gut-derived byproducts that accumulate in the systemic circulation. The results of our study will provide new insights into interventions, such as modulation of diet, that may alter the metabolome of the gut microbiota to help prevent and/or treat diseases associated with the development of CKD.

Public Health Relevance

Chronic kidney disease (CKD) may alter the homeostatic relationship between human hosts and their intestinal tract microbial inhabitants (i.e., the gut microbiota) due to the enhanced delivery of urea to the gut microbiota, alterations in diet, and the decrease in urinary excretion of small molecules produced by the gut microbiota. As a result, both the composition of the gut microbiota and its metabolite by-products may be altered in patients with CKD. Our overall study goal of investigating the role of the gut microbiota and gut-derived metabolites in altering the risk of major clinical outcomes associated with CKD will be accomplished using a longitudinal prospective cohort within the Chronic Renal Insufficiency Cohort (CRIC) Study, and a small additional population of CKD patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK107566-06
Application #
9980882
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Chan, Kevin E
Project Start
2016-09-20
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Tulane University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118