# Biological signatures of blueberry derived microbial metabolites

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $381,250

## Abstract

PROJECT SUMMARY/ ABSTRACT
 The goal of this study is to identify the molecular mechanisms by which blueberry-derived microbial
metabolites improve endothelial dysfunction during metabolic syndrome (MetS). We will employ multiomics
approaches to determine the vascular effects of blueberry metabolites. MetS is an important risk factor for
cardiovascular mortality and endothelial dysfunction plays a major role in the development of vascular
complications. Hyperglycemia, dyslipidemia, and pro-inflammatory cytokines contribute to endothelial
dysfunction in MetS. The vascular endothelium is covered with a glycocalyx which is comprised of proteoglycans
[core proteins with glycosaminoglycans (GAG)]. Intact glycocalyx of healthy vasculature acts as a protective
barrier and prevents endothelial dysfunction. Glycocalyx, importantly heparan sulfate proteoglycan (HSPG), is
severely compromised in MetS. Hence, preservation and restoration of HSPG to improve endothelial dysfunction
is a novel strategy to ameliorate vascular complications in MetS. Human studies support the vascular effects of
blueberry anthocyanins. Anthocyanins are extensively metabolized by the gut microbiota in humans, suggesting
their vascular benefits might be mediated by their microbial metabolites. Gut microbiota metabolize anthocyanins
and anthocyanins support the growth of microbes indicating a two-way relationship between them. Our
preliminary data show that :(i) blueberry supplementation improves vascular inflammation and dysfunction, and
increases the beneficial bacteria in diabetic mice; (ii) key blueberry metabolites attenuate palmitate-induced
endothelial inflammation and vascular dysfunction, and increase GAG production in endothelial cells (ECs)
isolated from diabetic patients. However, studies are lacking that identify (i) the microbial metabolites of
blueberries (Aim 1), (ii) the mechanisms by which blueberry-derived microbial metabolites improve endothelial
dysfunction in MetS (Aim 2), and (iii) the most active metabolites responsible for the vascular effects of
blueberries (Aim 3). Based on our preliminary studies, we hypothesize that blueberry attenuates endothelial
dysfunction in MetS by improving HSPG and/or acting on multiple targets which is mediated through the microbial
metabolites of blueberries. (1) Aim 1A: Determine the optimal dose of blueberry required to improve vascular
inflammation and dysfunction in mice with MetS using two established models [diabetic db/db mice and high fat
diet (HFD)-fed mice]. Aim 1B: Identify blueberry-derived `microbial metabolites'. (2) Aim 2: Determine the
mechanisms by which blueberry-derived microbial metabolites improve endothelial dysfunction in MetS. (3) Aim
3A: Determine the impact of circulating metabolites on endothelial dysfunction. Aim 3B. Identify the most active
microbial metabolite(s). We will use physiologically relevant models and state of the art techniques to evaluate
the mechanistic roles of microbial metabolites of ...

## Key facts

- **NIH application ID:** 10229449
- **Project number:** 5R01AT010247-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Anandh Babu Pon Velayutham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2018-09-21 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229449

## Citation

> US National Institutes of Health, RePORTER application 10229449, Biological signatures of blueberry derived microbial metabolites (5R01AT010247-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229449. Licensed CC0.

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