# Early Life Stress and Cardiovascular Disease Risk: Identifying the Role of Microbial Metabolites

> **NIH NIH K99** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $170,532

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Exposure to early life stress (ELS), including abuse, neglect, and household dysfunction, significantly
increases the risk of mental illness, chronic kidney disease, and cardiovascular disease (CVD) later in life. The
previously characterized effects ELS and chronic disease development in adults may have their origins in ELS-
dependent effects on composition and functions of the gut microbiota. The gut microbiota interact directly with
the host’s immune and neurological systems and microbial derived metabolites have been shown to mediation
cardiovascular function. My recently published research using a mouse model of ELS has determined that ELS
alters the gut microbiota independent of maternal inheritance. This suggests ELS-medicated endogenous
factors within the offspring are responsible for the ELS microbial phenotype. However, it remains unknown
whether ELS-mediated changes in the gut microbiota play a direct role in the genesis risk factors for CVD. This
proposal will address these knowledge gaps by identifying ELS-medicated factors that regulate the gut
microbiota and elucidating microbial-mediated pathways that lead to increased CVD risk due to ELS.
 Adolescents and young adults with ELS have increased arterial stiffness and systemic vascular
resistance. Using an established mouse model of ELS involving maternal separation, our novel data indicate
that ELS is also associated with increased arterial stiffness in adolescent and adult mice. Furthermore, ELS
induces superoxide production and endothelial dysfunction in adult mice. This suggests that vascular
dysfunction is an important mediator of ELS-induced CVD risk. Our new data in mice show that ELS leads to
reduced gut microbial diversity, lower circulating short-chain-fatty acids (SCFAs), and impaired gut barrier
function during adolescence. Gut microbial diversity is negatively associated with arterial stiffness in women
and reduced SCFAs are associated with hypertension and impaired gut barrier function. This suggests a role
for the gut microbiota in ELS-induced vascular dysfunction, though exact mechanisms remain undefined.
Therefore, the overall goal of this proposal is to elucidate mechanisms by which microbial metabolites
mediate ELS-induced aortic stiffening and endothelial dysfunction and examine the potential of diet in the early
intervention of CVD risk.

## Key facts

- **NIH application ID:** 10739155
- **Project number:** 1K99HL165091-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Keri Kemp
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $170,532
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10739155

## Citation

> US National Institutes of Health, RePORTER application 10739155, Early Life Stress and Cardiovascular Disease Risk: Identifying the Role of Microbial Metabolites (1K99HL165091-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10739155. Licensed CC0.

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