# Early Life Stress Patterning of the Gut-Brain Axis: An Intergenerational Approach

> **NIH NIH R03** · JOHNS HOPKINS UNIVERSITY · 2021 · $85,096

## Abstract

PROJECT SUMMARY
Adverse childhood experiences (ACEs), such as abuse or chronic stress, program a dysregulated
neuroendocrine-neuroimmune axis that persists through adulthood and promotes elevated inflammation. A
proinflammatory milieu during pregnancy may be particularly pernicious, with potential health effects on both
mother and offspring. In African American (AA) women, childhood stress is associated with poor infant
outcomes, independent of adulthood stress exposure. AA women have higher rates of ACE exposure and
greater physiologic vulnerability to the inflammatory impact of stress than Caucasian women, and double the
rate of preterm birth as Caucasians in the U.S., underlining the importance of studying stress and maternal-
offspring health in this population. Data from our laboratory suggests that the gut microbiome may be a key link
in the association between maternal ACE and elevated inflammation in pregnancy. While there are links
between gut microbial composition and elevated proinflammatory cytokines, a gap in the research remains in
establishing links from ACE to gut microbiome to inflammation, which our first aim addresses. Further, if ACE
is associated with an altered gut microbiome during pregnancy, does this altered microbiome pass to the
offspring during vaginal delivery? Our second aim addresses whether stress-induced alterations in the
maternal gut microbiome are passed to the offspring, assessing offspring gut microbial community composition
and metabolites (the metabolome). As the gut microbiome-metabolome shapes development of the offspring
immune system and makes nutrients available for brain development, its function has important implications for
offspring outcomes. Finally, our laboratory found that maternal dietary intake of omega-3 fatty acids may
ameliorate the effects of ACE on inflammation during pregnancy. In women with a history of multiple ACEs
(“high ACE”), those who consumed large amounts of omega-3 fatty acids had an inflammatory stress response
similar to that of women with no ACE history, while high ACE women with low omega-3 consumption had
elevated levels of proinflammatory cytokines. Our final aim assesses impact of maternal diet during pregnancy
on the relationship between gut microbiome and inflammation, with implications for future intervention work in
this high-risk pregnant AA population. To address these aims, we will study 200 mother-infant dyads from the
existing Children’s Hospital of Philadelphia (CHOP) Infant Growth and Microbiome (IGRAM) cohort, with
existing fecal and blood samples. We will measure gut microbial community composition at the sub/species
level using leading-edge shotgun metagenomics sequencing, gut metabolites (short chain fatty acids; SCFAs)
as an index of gut function, and serum proinflammatory cytokines in mothers and offspring. This would allow us
to model the complex relationships among maternal ACEs, gut microbiome, and inflammation, and the
relationship of these factors...

## Key facts

- **NIH application ID:** 10227802
- **Project number:** 5R03HD101336-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Liisa Victoria Hantsoo
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $85,096
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227802

## Citation

> US National Institutes of Health, RePORTER application 10227802, Early Life Stress Patterning of the Gut-Brain Axis: An Intergenerational Approach (5R03HD101336-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10227802. Licensed CC0.

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