# Role of the Gut Microbiota in Abdominal Aortic Aneurysm

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2020 · $658,280

## Abstract

ABSTRACT (Project Summary)
Rupture of abdominal aortic aneurysms (AAA) leads to sudden death in 15,000 to 30,000 men and women
each year in the US, and this number is growing due to both an increase in the elderly population and our
increasingly poor life-style choices, e.g. sedentary lifestyle and western diet, resulting in cardiovascular
disease. Known risk factors for AAA include tobacco use, hypertension, male gender, and cardiovascular
disease. However, the underlying cause of this condition is still poorly understood. Further, little progress has
been made to identify any pharmacologic treatments which may benefit these patients leaving surgery as the
only treatment option. Recent evidence has emerged that gut microbes resident in the human intestine can
promote several cardiovascular diseases. Specifically, nutrients present in high fat foods (phosphatidylcholine
and choline) can be metabolized by the gut microbial enzymes to generate trimethylamine (TMA), which is
further metabolized by the host hepatic enzyme Flavin-containing monooxygenase 3 (FMO3) to produce
trimethylamine N-oxide (TMAO). Our preliminary data demonstrates that circulating levels of TMAO are
associated with AAA diameter, growth, and severity in a human cohort. Further, we present extensive
preliminary studies demonstrating choline feeding augments a mouse model of aneurysm potentially via TMAO
production by the gut microbiome. The overall goal of this proposal is to determine how the gut microbiome-
derived metabolite TMAO contributes to the initiation and progression of AAA. Our two specific aims will (1)
examine the role of the gut microbiota in the initiation of AAA by investigating the TMAO meta-organismal
pathway; and (2) will determine whether inhibition of TMAO production attenuates the progression of
developed aneurysms. The long-term goals of this research are to increase our understanding of the effect of
gut microbiome-derived factors and their contribution to AAA in order to translate these findings into more
effective therapeutics to improve survival and quality of life for patients with this condition. We anticipate our
translational studies to reveal new molecular mechanisms linking gut microbe-derived factors to aneurysm,
which may ultimately be leveraged into the first ever gut microbe-targeted therapeutic and pharmaceutical
intervention for AAA.

## Key facts

- **NIH application ID:** 9972545
- **Project number:** 1R01HL147171-01A1
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Albert Phillip Owens III
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $658,280
- **Award type:** 1
- **Project period:** 2020-06-01 → 2024-05-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972545

## Citation

> US National Institutes of Health, RePORTER application 9972545, Role of the Gut Microbiota in Abdominal Aortic Aneurysm (1R01HL147171-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972545. Licensed CC0.

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