# Influence of Early Life Gut Microbiota of HIV-Exposed Uninfected Infants on Inflammation, Growth and Immunity to Enteric Pathogens

> **NIH NIH R21** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $243,050

## Abstract

Rates of perinatal HIV transmission have fallen substantially due to increased access to antiretroviral therapy
during pregnancy and breastfeeding. However, this has led to a growing population of infants who are HIV-
exposed but uninfected (iHEU). iHEU display heightened inflammation, immune activation and immune
exhaustion potentially driven by their altered gut microbiota. HIV exposure has also been linked to impaired
growth (stunting) in infants. Multiple studies have shown evidence of stunting in iHEU compared to HIV
unexposed infants (iHU). In addition, malnutrition studies have linked chronic intestinal inflammation, which also
associated with gut microbiota alteration, in infants to impaired growth. The mechanism(s) behind impaired
growth in iHEU are not understood. It is plausible that heightened intestinal inflammation in iHEU may associate
with stunting. However, whether the gut microbiota in iHEU causes impaired growth has not been formally tested.
Beyond growth, the gut microbiota impacts immune development. Specifically, microbiota composition early in
life imprint lasting immunological consequences. iHEU display high infectious morbidity including to enteric
pathogens. For example, studies have shown that iHEU exhibit high prevalence of enteropathogenic Escherichia
coli (EPEC) and Cryptosporidium spp compared to unexposed counterparts. The gut microbiota has been shown
to protect against enteric pathogens via various mechanisms including colonization resistance and alteration of
mucosal immunity. Whether gut microbiota in iHEU enhance susceptibility to enteric pathogens is unknown.
Human studies are based on correlations which limit ability to infer causation. We will utilize a germ-free neonatal
mouse model to investigate the causal role of the early stool microbiota in iHEU in driving these clinical
phenotypes. In addition, we will use a neonatal mouse model of EPEC to test causality between stool microbiota
and immunity to enteric pathogens. We hypothesize that the gut microbiota of iHEU early in life causes
inflammation, poor growth and impairs immunity to enteric pathogens. We propose to test this hypothesis
with the following specific aims.
Aim 1: To investigate whether the early life gut microbiota of iHEU causes intestinal and systemic inflammation
and impaired linear growth during infancy.
Aim 2: To investigate whether the early life gut microbiota of iHEU impairs immunity to enteric pathogens

## Key facts

- **NIH application ID:** 10898915
- **Project number:** 7R21AI179225-02
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Donald Nyangahu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $243,050
- **Award type:** 7
- **Project period:** 2023-08-03 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898915

## Citation

> US National Institutes of Health, RePORTER application 10898915, Influence of Early Life Gut Microbiota of HIV-Exposed Uninfected Infants on Inflammation, Growth and Immunity to Enteric Pathogens (7R21AI179225-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10898915. Licensed CC0.

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