# Prebiotic Activity of Tart Cherry and the Immunoregulation of Bone Homeostasis

> **NIH NIH R15** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2020 · $440,865

## Abstract

Project Summary/Abstract:
Worldwide, an estimated 1 in 3 women and 1 in 5 men over the age of 50 y experience an osteoporotic
fracture. In the U.S. alone, the impact on the healthcare system is $19 billion annually, but with our
aging population and poor compliance with existing pharmacological options these costs are expected
to escalate. Consequently, the search has continued for alternative strategies to prevent and treat
osteoporosis. Recent reports targeting the gut-bone axis have provided renewed interest in the role of
nutritional interventions. Compelling evidence has shown that probiotics increase short chain fatty
acids (SCFAs), which in turn promote the differentiation of T regulatory (TREG) cells that mediate
osteoprotective effects. The bone-protective benefits of classic prebiotics (i.e., fibers) have been
attributed to a SCFA-induced increase in intestinal calcium uptake; however, insights gained more
recently from studies of probiotics raise the question of whether prebiotics target gut commensal
microbiota and alter bone homeostasis by similar immunoregulatory mechanisms. The recent adoption
of a more comprehensive definition of prebiotics has revealed that natural products such as tart
cherries provide an excellent source of fructo-oligosaccharide, anthocyanin and phenolic acid, each
with notable prebiotic activity. Preliminary data from our lab will show that supplementing the diet
with tart cherry promotes bone accrual, protects against bone loss, increases SCFAs (e.g., butyrate), and
downregulates inflammatory processes in gut-associated lymphoid tissues. The goal of this project is to
determine the extent to which the prebiotic activity of tart cherry mediates it effects on bone via
butyrate-induced alterations in TREG cells. We hypothesize that the benefits of tart cherry
supplementation on bone are mediated, at least in part, by enhanced TREG differentiation resulting from
alterations in the gut microbiota and the consequent increase in butyrate production. The following
aims have been developed to test this hypothesis: Aim 1) To determine how dietary supplementation
with tart cherry alters bone homeostasis and the extent to which these effects are mediated by
alterations in TREG cells; and Aim 2) To investigate the role of butyrate derived from the gut microbiota
on this skeletal response. The proposed studies will advance our understanding of how the bioactive
components in tart cherry mediate their effects on the gut-bone axis in addition to providing an
excellent training opportunity for undergraduate researchers. Furthermore, these findings could
establish the foundation for future clinical studies designed to target the gut with prebiotics, which is in
line with our long-term goal of developing alternative therapeutic strategies for the prevention and
treatment of osteoporosis.

## Key facts

- **NIH application ID:** 10046896
- **Project number:** 1R15AT010725-01A1
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** STEPHEN L CLARKE
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,865
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046896

## Citation

> US National Institutes of Health, RePORTER application 10046896, Prebiotic Activity of Tart Cherry and the Immunoregulation of Bone Homeostasis (1R15AT010725-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10046896. Licensed CC0.

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