# Bifidobacterium infantis supplementation in early life to improve immunity in infants exposed to HIV: a randomized, placebo-controlled, double-blind trial

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2024 · $760,095

## Abstract

The early life microbiome plays a significant role in health and disease, including immune development and
maturation, and maternal microbiota is a major determinant of infant microbiota. Infants who are exposed to
HIV but uninfected (iHEU) are more vulnerable to disease, have stunted growth, altered gut microbiota and
poorer immunity, even when they are not infected with HIV themselves. In iHEU and mice we found that higher
relative abundances of Bifidobacterium longum subspecies infantis in the gut around time of Bacillus
Calmette–Guérin (BCG) vaccination results in improved cellular immunity later in life, which was accompanied
changes in gut metabolome, suggesting a link between B. infantis abundance or metabolites and T cell
immunity. We hypothesize that B. infantis supplementation in early life offers a therapeutic avenue to improve
immunity and subsequent health outcomes in iHEU. We thus propose to randomize 200 breastfed South
African iHEU into a placebo-controlled, double-blinded trial of B. infantis ECV001 (a commercially available
product with proven safety and health outcomes) versus placebo. The aims are to 1) compare gut microbial
structure and function longitudinally in iHEU randomized to receive B. infantis versus placebo in early life and
evaluate associations with stool metabolome. Infant stool will be analysed using shotgun metagenomics and
metabolome using semi-targeted metabolomics. The microbiome composition and function will be compared
between groups at birth, week 4, 7 and 36 of life, and correlated with stool metabolome at week 4. 2) To
compare gut mucosal integrity and regulatory versus inflammatory T cell ratios in iHEU who received early life
B. infantis versus placebo. At baseline, weeks 4, 7 and 36 markers of microbial translocation and systemic
inflammation will be assessed by ELISA and T cell phenotyping conducted using multi-parameter flow
cytometry. We will use an unsupervised self-assembly matching approach to compare T cell subsets and
correlate findings with measurements systemic markers in infants who received B. infantis versus placebo. 3)
To compare T cell responsiveness to BCG vaccination and linear growth in iHEU who received early life B.
infantis versus placebo. BCG vaccine responses will be measured at week 7 and 36 using a whole-blood-
assay and flow cytometry, and growth at week 36 using length for age Z scores, and compared cross-
sectionally between groups. BCG vaccine responses will be correlated with B. infantis abundance at all time
points. Finally, we will develop an integrative model on the effects of B. infantis supplementation on the health
of iHEU using data generated from all aims. Determining whether B. infantis ECV001, a readily available
intervention, is effective in improving gut health, inflammation, and immunity in iHEU, a growing and vulnerable
pediatric population, could result in improved clinical management and health outcomes of iHEU. This proposal
is highly relevant for sub-Sa...

## Key facts

- **NIH application ID:** 10838355
- **Project number:** 5R01HD109089-03
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Heather Beryl Jaspan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $760,095
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838355

## Citation

> US National Institutes of Health, RePORTER application 10838355, Bifidobacterium infantis supplementation in early life to improve immunity in infants exposed to HIV: a randomized, placebo-controlled, double-blind trial (5R01HD109089-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10838355. Licensed CC0.

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