# Interspecies microbial interactions in CKD

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $689,095

## Abstract

ABSTRACT
 Chronic kidney disease (CKD) is a gradual loss of kidney function, which affects an
estimated 37 million American adults, resulting in 14.6 deaths per 100,000 population. Once
kidney damage occurs, it impairs removal of uremic toxins, leading to further deterioration of
physiological functions and progression of renal failure. Surprisingly, many uremic toxins are not
produced by the body itself, but rather derived from the gut microbiota. CKD is associated with
changes in the composition of the gut microbiota (dysbiosis), which is characterized by an
increased abundance of Enterobacteriaceae in the fecal microbiota, a group of microbes known
to produce uremic toxins, such as indole. The objectives of this application are to understand the
ecological causes of dysbiosis in CKD on a molecular level and to determine whether dysbiosis
has a causative effect on CKD progression. Our central hypothesis is that elevated expression of
inducible nitric oxide synthase (iNOS) in the intestine fuels growth of Enterobacteriaceae by
anaerobic nitrate respiration. In turn, increased indole production by respiring Enterobacteriaceae
aggravates CKD disease progression. We will test different aspects of our hypothesis using the
logical and innovative approach outlined in the following specific aims. Specific Aim 1: Determine
the ecological causes of dysbiosis during CKD. Specific Aim 2: Determine whether dysbiosis has
a causative effect on CKD progression. The proposed work is innovative because it is among the
first to provide molecular insights into how changes in the microbiota composition occur in CKD,
and how microbiota changes are causatively linked to disease progression. Successful
completion of the proposed work will establish how CKD-associated host responses drive
changes in the ecology of the gut microbiota, which in turn set the stage for release of uremic
toxins by Enterobacteriaceae, thus accelerating CKD progression. This outcome will be of broad
significance for the rational design of new intervention strategies.

## Key facts

- **NIH application ID:** 10851184
- **Project number:** 1R01DK138912-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Andreas J Baumler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $689,095
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851184

## Citation

> US National Institutes of Health, RePORTER application 10851184, Interspecies microbial interactions in CKD (1R01DK138912-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10851184. Licensed CC0.

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