# Acute kidney injury and microbiome

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $611,713

## Abstract

Project Summary /Abstract
Acute kidney Injury (AKI) associated morbidity and mortality is a major clinical problem that involves multiple
overlapping pathophysiological mechanisms. Recent observations from our team and others demonstrated that
intestinal microbiota modulates AKI outcome, however the underlying mechanism involved in intestinal
microbiota-kidney crosstalk, especially during the recovery phase, remain poorly understood. Our working
hypothesis for this grant application is that gut microbiota induces specific changes in the kidney T cell population
to mediate AKI outcome and recovery. Furthermore, we hypothesize that short chain fatty acids (SCFAs)
produced by certain gut microbiota communicate with kidney tissue via specific smell receptors, such as G
protein coupled receptor 41 (Gpr41), olfactory receptor 78 (Olfr78) and Olfr558 present in the kidney. To test our
hypotheses, we will (AIM 1) immunophenotype kidney immune cells from wild type (WT), antibiotic treated (AB)
and germ free (GF) mice at baseline, during the early phase of AKI, and during recovery of ischemic and cisplatin
induced AKI. We will conduct mechanistic studies using T cell deficient mice, T cell antibody depletion and
adoptive transfer studies targeting select T cells (e.g. CD4, Tregs, CD3+CD4-CD8- double neg) to determine
roles of select T cells on microbiome effects on AKI. Metagenomic and metabolomics with focus on immune
inflammatory pathways will be measured in AKI and recovery for identification of microbial communities and
metabolites. We will also perform colonization studies with specific bacteria, anti-inflammatory stool (from
pregnant mice) and probiotics in AB treated, GF and WT mice. Furthermore, effect of endotoxin released from
leaking gut on renal immune cells population will be investigated in studies using toll like receptor 4 (TLR4)
deficient mice. To study the role of SCFA signaling receptors in intestinal microbiota–kidney crosstalk (AIM 2)
we will induce AKI in Gpr41-/-, Olfr78-/- and Olfr558-/- mice to delineate role of SCFA signaling during AKI
recovery. We will identify immune cell or resident kidney endothelium/epithelial source of SCFA interaction with
Gpr41, Olfr78 and Olfr558 by evaluating kidney and immune cell specific SCFA receptor deficient mice and
performing bone marrow transplants. Additionally, SCFA producing bacteria and exogenous SCFAs will be
administered to Gpr41-/-, Olfr78-/- and Olfr558-/- mice and its effect examined on AKI outcomes. To make our
lab studies more relevant to human AKI, we will (AIM 3) perform metagenomics of pre and post stool samples
and blood metabolomics from patients undergoing cardiac surgery to find gut microbiota differences between
those that develop AKI and those that are protected. We will investigate the effect of human microbiota from
patients that develop AKI in AB treated, GF mice and SCFA receptor deficient mice. Successful completion of
these studies will help understand immunological ef...

## Key facts

- **NIH application ID:** 10050192
- **Project number:** 1R01DK123342-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** HAMID RABB
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $611,713
- **Award type:** 1
- **Project period:** 2020-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050192

## Citation

> US National Institutes of Health, RePORTER application 10050192, Acute kidney injury and microbiome (1R01DK123342-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10050192. Licensed CC0.

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