# Multi-omic approaches to mechanisms of vitamin D, environmental influences, and the microbiome on asthma

> **NIH NIH UH3** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $2,629,203

## Abstract

PROJECT SUMMARY / ABSTRACT
Asthma and allergic diseases continue to be major public health problems resulting in significant disability and resource
utilization globally. Most asthma is diagnosed before the age of six. Thus, prenatal and early life exposures play an
important role in the development of asthma and allergies. On the basis of finding an inverse association between family
size and atopy, it was postulated that reduced microbial exposure in early life explains the epidemic of allergic diseases
(the “hygiene hypothesis”). The original hygiene hypothesis has undergone changes and refinement, and is now taken to
mean not just simply a reduced microbial exposure, but perhaps changes in the breadth and types of microorganisms
coupled with changing environments. The gut flora is, quantitatively, the most important postnatal source of microbial
stimulation of the immune system. Significant differences between the gut flora of children in industrialized and
developing nations suggest that the high prevalence of asthma in affluent nations may be due to changes in the
intestinal flora of young infants. This concept of “dysbiotic drift,” whereby environmental forces related to Westernized
lifestyles leads to a shift of the developing microbiota away from the norm, may explain why many chronic inflammatory
conditions, such as asthma, are associated with Westernized lifestyles. Dysbiosis is a potential mechanism by which the
environment interacts with the early developing immune system to program risk for chronic disease.
While there are a growing number of studies that are investigating the role of the intestinal microbiome in asthma,
these have examined stool samples obtained at one point in time. Since the intestinal microbiome undergoes rapid
changes before it becomes established between the ages of 1 and 3 years of life, longitudinal studies are needed.
Additionally, no studies have accounted for the host genetic background, which may determine both the development
of dysbiosis and who develops asthma when faced with dysbiosis. The overarching hypothesis of this proposal is that
vitamin D deficiency in the pre-, peri-, and immediate post-natal periods, in addition to host genetic influences, lead
to intestinal dysbiosis in early life. Dysbiosis, in the proper host genetic context, then increases the risk for
development of asthma. While we have collected information on a host of other relevant exposures, this proposal will
focus on vitamin D as the primary exposure of interest. We have put together 2 vitamin D clinical trial populations –
Vitamin D Antenatal Asthma Reduction Trial (VDAART) and Copenhagen Prospective Studies on Asthma in Childhood
(COPSAC2010) – with prospective collection of exposures during pregnancy and early life, that we will leverage to test our
hypotheses. This proposal is in response to FOA RFA-OD-16-004, Environmental Influences on Child Health Outcomes
(ECHO) Pediatric Cohorts (UG3/UH3).
In these cohorts, we will fir...

## Key facts

- **NIH application ID:** 10475748
- **Project number:** 5UH3OD023268-07
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** AUGUSTO A LITONJUA
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,629,203
- **Award type:** 5
- **Project period:** 2016-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475748

## Citation

> US National Institutes of Health, RePORTER application 10475748, Multi-omic approaches to mechanisms of vitamin D, environmental influences, and the microbiome on asthma (5UH3OD023268-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10475748. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*