# The role of the microbiome and other host related factors in determining urine oxalate levels

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $771,555

## Abstract

Oxalate is involved in the pathophysiology of kidney stones (KS) and chronic kidney disease
(CKD), which, respectively, affect more than 9% and 15% of the adult US population. Higher
urine oxalate (UOx) can lead to calcium oxalate KS and CKD incidence and progression. The
gut microbiome plays a key role in human oxalate homeostasis, which differs between stone
formers (SF) and non-stone formers (NSF). In SF, rates of oxalate absorption and endogenous
oxalate synthesis are higher than in NSF. The determinants of UOx and their interplay are still
unknown limiting our ability to develop therapeutics to treat hyperoxaluria. Our data demonstrate
oxalate degradation in the human intestine is performed by multiple bacterial species (the
oxalobiome) with variable contributions to global oxalate metabolism and that alteration of the
oxalobiome function is associated with higher UOx in SF. In mice, we showed that the gut
microbiota is an important determinant of UOx and colonization with an oxalate degrader
(Oxalobacter formigenes) led to lower UOx. We hypothesize that the gut microbiome is a
major determinant of UOx, and its manipulation can reduce UOx levels. The overarching
goal of this proposal is to better understand how gut microbial metabolism of dietary oxalate is
linked to UOx levels within a host and can serve as a potential therapeutic target. We propose
to leverage the rich resources available for participants in the Nurses' Health Study II (n = 584
women; 218 SF and 366 NSF) and the Health Professionals Follow-up Study (n = 308 men; 58
SF and 250 NSF), including existing and to be completed sequencing data from fecal samples,
existing genomic data, 24-hour UOx, validated dietary information, comorbidities, and
medication use. In Aim 1, we plan to investigate the metaorganismal oxalate degrading function
in determining UOx, and whether it differs in SF and NSF by performing additional sequencing
and analyzing metagenomes and metatranscriptomes from fecal samples to quantify the
oxalobiome function and then conduct comprehensive multi-layer microbiome data analysis
around the oxalobiome. In Aim 2, we will identify the interwoven role of gut microbiome, host
genetics, comorbidities, and dietary information in determining UOx. In Aim 3 we will test the
role of the oxalobiome in UOx excretion and the efficacy of several probiotic combinations in
reducing UOx. In these multidisciplinary, computational, translational, and animal-model based
investigations, we aim to reveal a role for the gut oxalobiome in urinary oxalate excretion with
the goal of developing therapeutic approaches for the treatment and prevention of the adverse
effects of oxalate in humans.

## Key facts

- **NIH application ID:** 10900154
- **Project number:** 1R01DK137473-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** GARY C. CURHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $771,555
- **Award type:** 1
- **Project period:** 2024-08-16 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900154

## Citation

> US National Institutes of Health, RePORTER application 10900154, The role of the microbiome and other host related factors in determining urine oxalate levels (1R01DK137473-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10900154. Licensed CC0.

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