# Exploring human milk oligosaccharides and malaria risk in breastfed infants

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $170,000

## Abstract

ABSTRACT
There is a significant burden of malaria in young African infants - the majority of whom are breastfed from birth up to 24
months. These `break through' malaria infections probably indicate incomplete protection by breastfeeding. There is a
significant gap in our knowledge about antimalarial immunity mediated by breastfeeding and the factors involved. Our
recent preliminary data demonstrated that high concentrations of specific human milk oligosaccharides (HMOs) in
Ugandan mothers' milk are differentially associated with malaria risk in their infants. HMOs represent the third most
abundant component in breast milk which, upon ingestion by infants, reach the systemic circulation where they directly
engage innate immune cells through specific surface receptors. Studies involving ex vivo stimulation of human cells and
cell lines demonstrated that HMOs modulate the functions of macrophages and monocytes in several ways. This includes
inducing anti-inflammatory or proinflammatory responses, inducing or inhibiting monocyte or macrophage activation,
inhibition of proliferation or migration, and enhancing phagocytosis. A human clinical trial involving infants fed 2'-
fucosyllactose (2'FL) in formula confirmed the anti-inflammatory effect of 2'FL. HMO-mediated modulation of
monocyte function is highly relevant to pediatric malaria which involves monocyte dysregulation and systemic
inflammation. Our long-term goal is to elucidate the role of HMOs in early innate immunity against malaria.
The objective of this project is to determine the relationship between HMOs in breast milk and infant blood, monocyte
function, and malaria outcomes in breast-fed infants. The central hypothesis is that direct HMO modulation of monocytes
tips the balance towards disease or protection during pediatric malaria and that differences in levels of specific HMOs are
linked to different malaria outcomes. This hypothesis will be tested in two Specific Aims. Aim 1: To recruit a birth cohort
and prospectively collect health metadata including malaria outcomes and concentrations of soluble monocyte activation
markers, cytokines and chemokines in infants. A birth cohort of 388 mother-infant pairs will be recruited and infants
followed over 18 months with blood sampling every month and during infant illness for malaria diagnosis, multiplex
bead-based cytokine and chemokine assays and ELISA for soluble monocyte activation markers. Aim 2: To measure
concentrations of HMOs in mothers' milk and infant plasma to assess their association with monocyte mediators and
malaria outcomes in infants. We will measure concentrations of HMOs in mothers' milk and infant plasma monthly and
during pediatric malaria attacks to identify HMOs that are associated with specific monocyte inflammatory cytokines and
chemokines and activation markers which are, in turn, linked to distinct malaria outcomes. To account for correlation
between multiple measurements in the same infant, the relationships betwe...

## Key facts

- **NIH application ID:** 10226366
- **Project number:** 5R21AI149452-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Lars Bode
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $170,000
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226366

## Citation

> US National Institutes of Health, RePORTER application 10226366, Exploring human milk oligosaccharides and malaria risk in breastfed infants (5R21AI149452-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10226366. Licensed CC0.

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