# Alcohol-induced Gut Dysbiosis and Cardiovascular Disease

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2022 · $429,615

## Abstract

PROJECT SUMMARY
Hazardous alcohol use (HAU) leads to tremendous morbidity and mortality in millions of individuals in the United
States and worldwide annually. The cognitive, neuronal, and psycho-social aspects of alcohol use have been
well established. More recently, clinical, and basic research has begun to understand the role in which HAU
contributes to gut dysbiosis, which plays a significant role in one’s overall health status. Furthermore, a large
portion of deaths associated with alcohol use are related to digestive diseases. HAU predisposes and contributes
to the manifestation of several comorbidities, like hypertension, metabolic syndrome, and diabetes mellitus which
drive and exacerbate vascular dysfunction and cardiovascular disease (CVD). Previous research has
demonstrated that the gut microbiome too plays a critical role in the diagnosis and prognosis of individuals with
established CVD. Increased levels of circulating trimethylamine-N-oxide (TMAO), a gut derived metabolite, has
been shown to drive the development of atherosclerotic heart disease. However, the relationship between HAU-
induced gut dysbiosis and its’ metabolites towards vascular and CV function is not well-defined. We hypothesize
that HAU-induced gut dysbiosis leads to endothelial dysfunction and increased risk of CVD via gut-
derived metabolites (i.e., TMAO). Furthermore, we believe that HAU-induced gut dysbiosis exacerbates
the progression of heart failure and that gut microbiota-targeted therapies (MBTT) will restore vascular
function thereby improving CV health in the setting of HAU. Through utilization of mouse models of HAU
and microbiota adoptive transfer we plan to execute a series of studies that demonstrate HAU-induced dysbiosis
and CV-related pathology are related; moreover, that the dysbiotic microbiome is sufficient to cause the vascular
dysfunction and increased risk of CVD. We plan to utilize metagenomics, metabolomics, and cardiovascular
function assessment to demonstrate the causal relationship between HAU, the gut microbiome and CVD. We
will then investigate the effects of prior HAU gut dysbiosis on the progression of heart failure in a murine model
of myocardial ischemia-reperfusion (MI/R). This will answer questions regarding the predisposition of individuals
who participate in HAU and their risk for worsening CV outcomes after MI/R-induced heart failure. Concurrently,
we will examine continuous HAU prior to and after MI/R-induced heart failure to understand if HAU leads to
increase morbidity or mortality in the presence of CVD. Successful completion of these studies will significantly
advance our understanding of the pathology of alcohol-induced gut dysbiosis and its’ effects on vascular and
cardiac function.

## Key facts

- **NIH application ID:** 10412366
- **Project number:** 1R01AA029984-01
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Thomas E. Sharp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $429,615
- **Award type:** 1
- **Project period:** 2022-05-05 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412366

## Citation

> US National Institutes of Health, RePORTER application 10412366, Alcohol-induced Gut Dysbiosis and Cardiovascular Disease (1R01AA029984-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10412366. Licensed CC0.

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