# Impact of L. plantarum 299v Supplementation on Endothelial Function and Systemic Inflammation

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $730,464

## Abstract

Recent human studies report an emerging relationship between the gut microbiota and its metabolites with the
development of atherosclerotic disease and adverse cardiovascular (CV) events. However, critical knowledge
gaps must be bridged to translate these foundational works into specific, gut microbiota-targeted interventions
to reduce CV risk. These include 1) identifying mechanisms by which a selected intervention impacts the
vascular endothelial function and mediators of atheroma formation and 2) identifying differences in the impact
of a selected intervention on key populations with known differences in gut flora (including sex and obesity
status differences). This proposal will address these issues for L. plantarum 299v (Lp299v) supplementation.
Our preliminary data in 20 men with coronary artery disease (CAD) suggest that probiotic supplementation with
Lp299v has a strong and favorable impact on the vascular endothelium and a strong anti-inflammatory effect
on inflammatory cells critical to the development of endothelial dysfunction and atherosclerosis. Our
preliminary data suggest obese CAD patients derive the greatest benefit, but whether the favorable impact of
Lp299v supplementation systematically differs in women or in obese humans with CAD remains unknown and
will be the foci of Aims 1 and 2. Our preliminary data also show improved endothelium dependent vasodilation
and reduced systemic inflammation occur concomitantly with changes in the concentrations of circulating
short-chain fatty acid (SCFAs)– known systemic metabolic products of the gut microbiota. In animal models,
SCFAs cause endothelium-dependent vasodilation by activating G protein-coupled receptor 41 (FFAR3).
Whether this novel mechanism is relevant in humans with CAD remains unknown. Our preliminary data shows
Lp299v supplementation increases circulating propionate, a three-carbon SCFA. Additionally, post-
supplementation plasma reversed impaired endothelium-dependent vasodilation in resistance arteries from
CAD patients in an eNOS- and FFAR3-dependent manner. FFAR3's role in endothelium-dependent
vasodilation responses to Lp299v is a focus of in Aim 2. In Aim 3, we will test whether Lp299v
supplementation reduces pro-inflammatory signaling in human mononuclear cells known to contribute to
atherosclerosis formation and disease activity and whether FFAR3 activity is involved in this effect. The
application employs an innovative mix of translational investigations. We combine a randomized clinical trial to
study sex- and BMI-specific effects of Lp299v on vascular function using brachial artery ultrasound with critical
molecular and pharmacological studies targeting FFAR3 expression and activity in intact human vessels and
mononuclear cells. Additionally, we will employ innovative plasma-induced transcription studies and pathway
analyses to determine the impact of supplementation on whole genome transcription in human mononuclear
cells [lymphocytes (T-cell, B-cell, and NK ce...

## Key facts

- **NIH application ID:** 9898445
- **Project number:** 5R01HL144098-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Michael E Widlansky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $730,464
- **Award type:** 5
- **Project period:** 2019-03-22 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898445

## Citation

> US National Institutes of Health, RePORTER application 9898445, Impact of L. plantarum 299v Supplementation on Endothelial Function and Systemic Inflammation (5R01HL144098-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898445. Licensed CC0.

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