# Role of the human gut microbiome and related metabolites for causally mediating vascular endothelial function

> **NIH NIH F31** · UNIVERSITY OF COLORADO · 2022 · $39,259

## Abstract

PROJECT SUMMARY/ABSTRACT
The purpose of this F31 application is to provide support for Ms. Abigail Casso, a 2nd year PhD student in Dr.
Douglas Seals’ (sponsor) laboratory at the University of Colorado Boulder, to conduct research and training
that will prepare her to become an independent investigator in the field of translational cardiovascular (CV)
aging research aimed at the prevention and treatment of age-related CV diseases (CVD). As part of her
proposed training plan, she aims to both refine research skills presently under development and learn a variety
of new technical, conceptual, and professional skills, including the use of preclinical mouse models and gaining
new experiences using human biospecimens, cell culture bioassays, and metabolomics approaches. Her
proposed research project seeks to investigate the role of age-related changes in the human gut microbiome
and circulating gut microbiome-derived metabolites in impairing vascular endothelial function. Gut microbiome
composition is uniquely altered with CVD and aging, and age-related changes in circulating concentrations of
certain gut-derived metabolites have been related to CVD. However, whether these age-related changes
causally impair endothelial function is unknown. Guided by strong preliminary data, Ms. Casso will determine:
(Aim 1) If age-related changes in the human gut microbiome impair endothelial function due to increased
oxidative stress and reduced nitric oxide bioavailability using innovative “humanized” mouse models and ex
vivo “pharmaco-dissection” techniques; (Aim 2A) The effect of age-related, gut microbiome-induced changes in
plasma circulating factors on endothelial function using cell culture bioassays; (Aim 2B) Which circulating
metabolites are altered by the aging human gut microbiome via targeted metabolomics; and (Aim 3) If specific
gut-derived metabolites that are increased in circulation with age directly induce endothelial dysfunction using
cell culture and isolated vessel approaches. The expected results will identify novel gut microbiome-related
and circulating gut-derived metabolite modulators of endothelial function and may facilitate translation of these
metabolites as new therapeutic targets for prevention and treatment of age-related endothelial dysfunction.
Overall, the proposed research has the potential to address important NHLBI Strategic Vision research
priorities, including: 1) investigate new pathobiological mechanisms important to the onset of CVD; and 2)
identify novel therapeutic targets to prevent and treat CVD113. Dr. Seals is an internationally recognized and
NIH-funded scientist with a strong history of successful mentoring in translational CV research, particularly in
the emerging field of “vascular aging”. Under his supervision and with the guidance of content expert co-
mentors Drs. Vienna Brunt, Angelo D’Alessandro, and Tiffany Weir, Ms. Casso will be able to successfully
complete the proposed research and training plan, facilita...

## Key facts

- **NIH application ID:** 10463449
- **Project number:** 1F31HL160173-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Abigail Grace Longtine
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,259
- **Award type:** 1
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463449

## Citation

> US National Institutes of Health, RePORTER application 10463449, Role of the human gut microbiome and related metabolites for causally mediating vascular endothelial function (1F31HL160173-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10463449. Licensed CC0.

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