# Development of allergy in offspring is enhanced by maternal eicosanoids and lung microbiota composition dysbiosis.

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $805,935

## Abstract

The greatest risk factor for development of allergies and asthma in offspring is a parental history of allergic
disease. Maternal transmission of reactivity that is not specific for allergen has been demonstrated in patients
and animal models. We demonstrated that there are increased numbers of subsets of dendritic cells (DCs) in
the fetal liver and offspring of allergic mothers. In preliminary animal studies, intratracheal transfer of lung
dendritic cells (DCs) or lung microbiota from neonates of allergic mothers transfers allergen responsiveness to
recipient neonates of non-allergic mothers. The mechanisms for regulation of offspring DCs and allergy by
factors from allergic mothers are not well defined. We propose the novel concept that increases in the
eicosanoids dihydroxyeicosatrienoic acids (DHETs) in allergic mothers are transported to the offspring, where
the DHETs regulate development of lung microbiota dysbiosis and offspring responsiveness to allergens. In our
preliminary lipidomics analyses, DHETs but not other eicosanoids were elevated in plasma of allergic mothers
and in fetuses, suggesting a potential function of this eicosanoid in development of allergy. In preliminary studies,
the development of bone marrow-derived DCs (BMDCs) was increased in vitro by DHET; also human cord blood
DHET levels correlated with infant wheeze. However, regulatory functions of maternal DHETs in the
development of offspring DCs and allergy are not known. Unknown are mechanisms for 1) maternal increases
in DHET, 2) DHET regulation of DC development in offspring, and 3) the reciprocity between lung microbiome
and host eicosanoid metabolism. Our long-term goal is to identify mechanisms for maternal DHET regulation
of offspring development of allergic responses. As a step towards our goal, our central HYPOTHESIS is that
increases in DHET levels in allergic mothers regulate the development of offspring numbers of pro-allergic DC
subsets, lung microbiota dysbiosis, and responses to allergen early in life. We will test our central hypothesis
with the following aims: Aim 1. Test the hypothesis that, a mechanism for increasing responsiveness to allergen
in offspring of allergic mothers is increased maternal lung DHETs that are transferred in utero to the fetus and in
milk to neonates. Aim 2. Test the hypothesis that increased levels of DHETs in allergic mothers is a mechanism
for increased hematopoiesis of fetal liver and pup bone marrow DC subsets and DC function in allergic
responses. We will also determine whether human cord blood plasma DHETs associate with infant atopy and
DC numbers. Aim 3. Test the hypothesis that increased DHETs of allergic mothers is a mechanism for induction
of maternal and neonate lung microbiome dysbiosis, thereby increasing the abundance of lung bacteria that
metabolize DHETs that then sustain increased offspring DC responsiveness to allergen. In human infants, we
will determine whether cord blood eicosanoid profiles associate with ...

## Key facts

- **NIH application ID:** 10792346
- **Project number:** 1R01AI180448-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** JOAN M COOK-MILLS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $805,935
- **Award type:** 1
- **Project period:** 2023-11-08 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792346

## Citation

> US National Institutes of Health, RePORTER application 10792346, Development of allergy in offspring is enhanced by maternal eicosanoids and lung microbiota composition dysbiosis. (1R01AI180448-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10792346. Licensed CC0.

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