# Aerosolized Nicotine Modulation of Host Inflammation and Microbiota Dysbiosis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $381,250

## Abstract

The use of aerosolized nicotine products, mostly electronic nicotine delivery systems (ENDS), are growing
in popularity and especially among younger individuals who have not necessarily used tobacco products previously.
We know little about the impact this has on their future health landscape. Challenges to our understanding of the
unique concerns ENDS present to health include their highly variable and inconsistent formulations. Despite this
variability, ENDS share in common the delivery of the biologically active component nicotine, which is present in
relatively high purity and concentration. This proposal will focus on examining the biologic effects of nicotine that
are unique to delivery by aerosolization (aeroNic) and inhalation. Our group has studied the impact of nicotine on
both peripheral immune and central processes leading to addiction since the original cloning of the nicotinic
acetylcholine receptors (nAChR). Because the effects of nicotine are highly dependent upon its route of delivery, we
have first developed a reliable method of aeroNic administration to the mouse that produces quantitative uptake and
kinetics comparable to those in humans. The experimental focus will apply this AeroNic delivery system to define
its impact on mouse inflammatory stasis in the lung and gastrointestinal (GI) tract, and determine how this modifies
the inflammatory response to challenge of the lung by either acute lung injury (ALI) or to allergic eosinophilic
inflammation (AEI; a model of asthma). This analysis will be greatly facilitated through application of genetic tools
that manipulate signaling through nicotine's principal target in peripheral cells, the nAChRalpha7 (α7). This
includes how nicotine couples to specific calcium signaling networks to modulate these pro-inflammatory responses.
In preliminary studies, aeroNic actions through α7 calcium-coupled mechanisms in the lung reduce inflammatory
responsiveness and alter epithelial cell signaling networks such as those controlling mucin production. Most recently
we have discovered a concurrent and robust impact by aeroNic on microbiota dysbiosis. The experiments proposed
build upon these preliminary and published findings to test the project hypothesis: Aerosolized nicotine acts to
depress lung responsiveness to ALI and to AEI through modifying α7 calcium signaling networks controlling
normal modulation of immune - epithelial - microbiota interactions. This will be tested in experiments outlined in
three interactive Specific aims. Aim 1 will measure how aeroNic alters the mouse microbiota and if dysbiosis is
permanent. Aim 2 will define transcriptional signaling networks and proteomic mechanisms through which aeroNic
acts through α7 to modify normal epithelial cell function. Aim 3 will define how aeroNic modifies the lung/GI axis
stasis through modifications of mucosal immune cells known to regulate both ALI and AEI. At the conclusion of
these experiments we will have a clear understanding of ...

## Key facts

- **NIH application ID:** 10071189
- **Project number:** 5R01HL135610-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** LORISE C GAHRING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071189

## Citation

> US National Institutes of Health, RePORTER application 10071189, Aerosolized Nicotine Modulation of Host Inflammation and Microbiota Dysbiosis (5R01HL135610-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071189. Licensed CC0.

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