# Dietary Etiologies of Heart Disease

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2022 · $738,932

## Abstract

Coronary heart disease (CHD) remains the major health threat in the U.S. The effectiveness of CHD
prevention measures, such as dietary and lifestyle interventions vary greatly between individuals and may be
ascribed partly to differences in gut microbiome composition and function. The proposed research aims to
elucidate a critical metabolic pathway through which human microbiome may contribute to the CHD etiology
and account for the between-person responses to diet and lifestyle choices. Specifically, we aim to evaluate,
prospectively, the association of the estimated exposure to lipopolysaccharide (LPS), a major component of
the Gram-negative bacteria membrane, on CHD risk. We will also examine dietary, lifestyle, and microbial
predictors of LPS exposure and create an “empirical metabolic endotoxemia index”. Human LPS-infusion
experiments clearly demonstrate that LPS exposure induces potent innate immune reactions, including
inflammation and recruitment of leukocytes to endothelium, and predisposes humans to an elevated risk of
developing atherosclerosis. Circulating LPS concentrations are challenging to measure in large-scale human
population studies due to a short half-life and variability in assay effectiveness due to daily fluctuations and
interference from proteins in blood samples. More reliable biomarkers, including LPS binding protein (LBP) and
soluble cluster of differentiation 14 (sCD14), characterize LPS exposure, but have yet to be systematically
examined in prospective epidemiological studies with documented incident CHD. Further knowledge gaps
include a comprehensive evaluation of microbial composition and functional potential in relation to LPS
exposure. To address these scientific gaps directly, we aim to 1) evaluate LBP and sCD14 in relation to CHD
risk, 2) examine dietary and lifestyle predictors of LBP/sCD14 and derive an empirical metabolic endotoxemia
index of these biomarkers, 3) establish temporal relationships of changes in the empirical index with changes
in LBP/sCD14 levels, as well as CHD incidence, and 4) investigate the role of the microbiome in determining
circulating levels of LBP/sCD14 and their impact on mediating diet/lifestyle associations. These aims will be
realized among men and women participating in the Health Professionals Follow-up Study (HPFS) and the
Nurses’ Health Study II (NHSII), who provided multiple blood and fecal samples. In addition to stored
biospecimens, these studies also offer rich, existing data, including gut metagenome and metatranscriptome
data, dietary assessments by 7-day diet records, and three decades of follow-up of diet, lifestyle, and CHD
incidence, that allow us to examine the aims in an efficient and comprehensive manner. Data to be generated
from this project will provide novel evidence that elucidates the complex inter-relationships between
diet/lifestyle, microbial composition and functional potential, LPS exposure, and CHD incidence. The evidence
will also inform the develo...

## Key facts

- **NIH application ID:** 10474319
- **Project number:** 5R01HL035464-31
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** ERIC B RIMM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $738,932
- **Award type:** 5
- **Project period:** 1985-12-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474319

## Citation

> US National Institutes of Health, RePORTER application 10474319, Dietary Etiologies of Heart Disease (5R01HL035464-31). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10474319. Licensed CC0.

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