# Microbial Dysbiosis and Epithelial Dysfunction in Vitamin A-deficient Lungs

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $18,707

## Abstract

Abstract
Once believed to be sterile, recent studies now show microbes inhabiting healthy lungs that are dysregulated in
patients with chronic obstructive pulmonary disease (COPD), asthma, tuberculosis (TB), and SARS-CoV-2
infection. Malnourished patients have an increased risk of respiratory infections and pathogenesis according to
recent studies, indicating a potential link between metabolic status and lung homeostasis. These and other
studies indicate the presence of host-microbe-vitamin A interactions that are present in the lung and influence
the respiratory immune response, however details of whether changes to the lung microbiome is a cause or
consequence of lung pathology, or whether retinoic acid (RA) – the bioactive metabolite of Vitamin A – can
directly influence the lung microbiome in a host-independent manner are largely unknown. We hypothesize that
dietary VAD-induced airway epithelial remodeling promotes microbial dysbiosis in the lung, further
perpetuating respiratory epithelial dysfunction via host-microbe interactions. Aim 1 will determine whether
dietary VAD directly alters metabolic pathways of opportunistic microbes found upregulated in the lower
respiratory tract (LRT) of adult VAD mouse lungs. Our Microscopy core facilities offer state-of-the-art
microscopes designed to capture high-quality fluorescent images that will enable us to identify microbial
composition, protein expression, and localization within the airway (1.1). Using qRT-PCR machines freely
accessible to me in the Pulmonary Center, we will measure changes in relative abundance of the opportunistic
microbes upregulated in VAS and VAD lungs at 3 weeks and 8 weeks post-dietary modulation (1.2). Aim 2 will
determine whether locally-derived vs. distally-derived metabolic changes in the host could influence airway
epithelial remodeling in the lower respiratory tract. We will measure ciliary motility in tracheal explants of VAS
and VAD lungs using a ciliary motility protocol already completed by our laboratory (2.1). We will also investigate
whether microbes have the ability to influence epithelial remodeling and ciliary function independent of host
metabolic status. We aim to expose VAS and VAD tracheal explants to microbes from opposing diets in-vitro
(2.2) and repeat the ciliary motility technique proposed in Aim 1. Our lab’s metatranscriptomic work paired with
the Pulmonary department’s proven expertise in intratracheal viral injections and cell culture techniques makes
this sub-aim easily achievable within the proposed time frame. Aim 3 will identify mechanisms associated with
microbial metabolic functions that are dysregulated in the absence of vitamin A. We will measure RNA transcripts
of our upregulated microbes via qRT-PCR gathered from our explanted tissues mentioned in Aim 2 (3.1). We
will also investigate microbe-microbe and microbe-environment interactions using an in-silico community-based
modeling program called COMETS (3.2), a platform created by our c...

## Key facts

- **NIH application ID:** 10894604
- **Project number:** 5F31HL162523-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Kiloni Quiles
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $18,707
- **Award type:** 5
- **Project period:** 2023-04-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894604

## Citation

> US National Institutes of Health, RePORTER application 10894604, Microbial Dysbiosis and Epithelial Dysfunction in Vitamin A-deficient Lungs (5F31HL162523-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894604. Licensed CC0.

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