# Exploring Associations between Human Milk Oligosaccharides and Atherosclerosis Risk Factors in Infancy and Early Childhood

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $171,743

## Abstract

ABSTRACT
Cardiovascular disease (CVD) is the leading cause of mortality, accounting for over a third of all deaths globally.
CVD is caused by atherosclerosis, a complex chronic inflammatory disorder that results from chronic damage to
the arterial wall by inflammation and lipid accumulation. Atherosclerosis begins in early life and is essentially
universal by early adulthood. Thus, there is broad consensus that CVD prevention should begin early when
adverse trajectories may be most modifiable – potentially as early as during infancy. Epidemiological data show
that breastfed infants are at lower risk of developing CVD later in life, however, the protective components in
human breastmilk and underlying mechanisms that contribute to the beneficial effects of breastfeeding remain
unknown. After lactose and lipids, human milk oligosaccharides (HMOs), a group of complex carbohydrates,
are the third most abundant component of human breastmilk. HMOs – either directly, or indirectly through
shaping the infant gut microbiome – can impact infant inflammation and lipid metabolism, the two key contributors
to atherosclerosis and CVD. In fact, our preliminary data shows that mice that received the HMO 3’-sialyllactose
(3’SL) with the dam’s milk during the breastfeeding period had significantly lower plasma triglyceride and
cholesterol levels and developed less atherosclerosis later in life. Here, we aim to explore whether these
observed beneficial effects translate from mice to humans. Based on the finding that HMO composition varies
between women and has been associated with several infant health and disease outcomes, we propose to test
the hypothesis that HMO amount and composition associate with early preclinical markers of CVD and metabolic
risk, and markers of inflammation from birth to early childhood. We will leverage the extraordinary resources of
the Barwon Infant Study (BIS), one of the most comprehensive pre-birth cohort studies of cardiometabolic and
inflammatory phenotypes in the world, apply state-of-the-art technology to measure HMO composition in
biobanked breastmilk and infant plasma samples, and test whether HMO concentrations associate with infant
lipidomic, metabolic, and cardiovascular phenotypes (AIM 1) as well as infant markers of inflammation (AIM 2).
Knowledge gained from the successful completion of the proposed project will add to the existing preclinical data
that established causal relationships. Together, the results will greatly enhance our understanding why breastfed
infants are at lower risk of later CVD and form the basis for early life interventions. This is particularly timely as
HMOs like 3’SL are now synthesized in bioengineered microbes and stand ready as new, inexpensive, scalable
and safe options to help prevent CVD early in life when adverse trajectories may be most modifiable and help
address the substantial and increasing health and economic costs of CVD.

## Key facts

- **NIH application ID:** 10491367
- **Project number:** 5R21HD105186-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Lars Bode
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $171,743
- **Award type:** 5
- **Project period:** 2021-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491367

## Citation

> US National Institutes of Health, RePORTER application 10491367, Exploring Associations between Human Milk Oligosaccharides and Atherosclerosis Risk Factors in Infancy and Early Childhood (5R21HD105186-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10491367. Licensed CC0.

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