# Role of the Gut Microbiome in Polycystic Ovary Syndrome

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $29,107

## Abstract

Project Summary/Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women
worldwide. In addition to infertility, many women with PCOS have metabolic abnormalities that result in an
increased risk of type 2 diabetes and cardiovascular disease. Studies have shown that the large intestine
contains a complex community of microorganisms (the gut microbiome), that the gut microbiome is altered in
humans with metabolic disorders such as obesity and type 2 diabetes, and that changes in the gut microbiome
may contribute to metabolic dysregulation. Two recent clinical studies reported that changes in the gut
microbiome were associated with PCOS. In addition, we and others demonstrated that the gut microbiome
composition was significantly altered in rodent models of PCOS. Our preliminary data with fecal microbiome
transplantation in germ-free mice as well as co-housing a PCOS mouse model with healthy mice suggests that
the gut microbiome plays a causal role in PCOS and that manipulation of the gut microbiome may improve
PCOS symptoms. In addition, studies demonstrated that serum LBP is increased in women with PCOS and
PCOS mouse models, suggesting that gut permeability may be altered in PCOS. Collectively, these studies
suggest that a microbial imbalance, or “dysbiosis”, in the gut may contribute to the development and pathology
of PCOS. Studying the role of the gut microbiome in a PCOS mouse model has several advantages for
mechanistic studies including the ability to control for diet and genetics, to use gnotobiotic (germ-free) mice
that lack a microbiome to test causality and to knockout genes of interest. We propose to use the letrozole-
induced PCOS mouse model to test the hypothesis that androgen action via the androgen receptor
results in dysregulation of the gut microbiome and gut epithelial function, which in turns contributes to
the development and pathology of PCOS. In Aim 1, we propose to use the androgen receptor antagonist,
flutamide to determine if the androgen receptor is necessary for changes in the gut microbiome, gut
permeability and the metabolic phenotype. In Aim 2, we will use germ-free mice to determine whether the gut
microbiome is necessary and sufficient for development of a metabolic phenotype. Finally, in Aim 3, we will use
fecal microbiome transplantation to ascertain whether modulation of the gut microbiome can improve PCOS
reproductive or metabolic phenotypes. In addition, we will use metagenomics coupled with transcriptomics to
identify which bacterial strains and functions are altered in the letrozole-induced PCOS mouse model in order
to identify potential pre- or probiotic therapeutic targets. Results from this proposal have the potential to answer
fundamental questions concerning the role of the gut microbiome in the development and pathology of PCOS
and expedite development of novel treatment options for women with PCOS (e.g., pre- or probiotic therapies).

## Key facts

- **NIH application ID:** 10329272
- **Project number:** 3R01HD095412-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Varykina G Thackray
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $29,107
- **Award type:** 3
- **Project period:** 2019-02-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329272

## Citation

> US National Institutes of Health, RePORTER application 10329272, Role of the Gut Microbiome in Polycystic Ovary Syndrome (3R01HD095412-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10329272. Licensed CC0.

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