# Microbiome-driven immune changes and growth stunting in HIV-exposed uninfected children

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $792,925

## Abstract

PROJECT SUMMARY
Despite increasing access to antiretroviral therapy (ART) in pregnancy, the >1 million children born annually to
pregnant people with HIV (PPHIV) who are HIV-exposed but uninfected (HEU) remain at >2-fold higher risk of
growth stunting and infectious morbidity than HIV-unexposed children. Though the origins of adverse HEU child
health outcomes are poorly understood, mounting evidence suggests that abnormal microbiome development
may play a key role. However, the mechanisms remain elusive, and a better mechanistic understanding is
essential to improve care. Our overarching goals are to identify clinical, environmental, diet, and epidemiologic
features associated with growth stunting in HEU children, characterize mechanisms of host-microbe
communication, and link gut microbiome profiles to immune development in growth stunted HEU children using
a multi’omics approach. To do so, we will leverage data, biobanked, and newly collected samples from an
ongoing prospective longitudinal birth cohort in Uganda to relate growth stunting, diarrheal disease burden, and
adverse clinical outcomes to microbiome-driven changes in HEU child immunity. Innovation: Our disease model
examining and characterizing relationships between transferred maternal immunity, child gut microbiome and
immune profile development, and childhood growth stunting is novel, highly relevant, and conceptually innovative.
Distinct advantages of our proposed research include 1) simultaneous comparison of samples from HIV-exposed
and -unexposed groups to minimize confounding, 2) rich clinical, epidemiologic, and environmental exposure
data in a well-characterized longitudinal cohort, 3) integrated multi’omics approach leveraging metagenomics,
metabolomics, and immun’omics, to identify novel mechanisms of growth stunting and immune development.
Investigators: Our interdisciplinary team with expertise in epidemiology, birth cohorts and infectious diseases
(Bebell); immunology (Alter, Bernshtein), multi’omics (Mehta, Chan, Huttenhower) is well-poised to complete this
work. Approach: We will leverage biobanked samples and extend follow-up of enrolled mother-child dyads in
Dr. Bebell’s (K23AI138856) birth cohort, Dr. Bernstein’s adaptations of the Systems Serology platform to enteric
organisms, and Dr. Mehta’s established multi’omics laboratory and data pipeline infrastructure to elucidate the
effects of maternal HIV exposure and microbiome composition on child growth and immune development through
age 5 via these Specific Aims: 1) Identify clinical metadata features associated with growth stunting in HEU
children with fine resolution; 2) Characterize gut microbiome features associated with growth stunting in HEU
children and establish mechanisms of host-microbe communication using metabolomics; 3) Define alterations in
transplacental antibody transfer and breast milk antibody composition specific to pathogenic and non-pathogenic
gut organisms in PPHIV and growth-stunted HEU childr...

## Key facts

- **NIH application ID:** 10840355
- **Project number:** 5R01HD112302-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Lisa M Bebell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $792,925
- **Award type:** 5
- **Project period:** 2023-05-11 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840355

## Citation

> US National Institutes of Health, RePORTER application 10840355, Microbiome-driven immune changes and growth stunting in HIV-exposed uninfected children (5R01HD112302-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10840355. Licensed CC0.

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