# The Exposome and Lung Bacterial Infection: Role of Liver and Gut-derived Extracellular Vesicles

> **NIH NIH P50** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $241,761

## Abstract

Pneumonia is one of the leading causes of morbidity and mortality, particularly in older individuals. Importantly,
alcohol misuse has been associated with increased pneumonia for over 200 years. While the role of alcohol in
bacterial pneumonia susceptibility and severity remains to be fully understood, it is essential to define the at-
risk conditions and unique needs of those who misuse alcohol and to do so immediately to optimize clinical
care. Disease is impacted by the sum of all environmental exposures during one’s life. Collectively referred to
as the exposome, little alcohol-mediated lung injury has taken into consideration such real-world complexity. In
this 5-year project, we will investigate the alcohol exposome in lung bacterial infections. Compared to the
general public, those with alcohol use disorders (AUD) can be characterized by heavy cigarette smoking
leading to pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD), a major co-
morbidity for pneumonia. Likewise, nutritional deficiencies play an important role in disease pathogenesis. Our
knowledge about how such exposome characteristics impact alcohol-mediated lung injury is limited. However,
results from our previous lung alcohol research have already demonstrated that AUD are associated with cilia
dysfunction. Our results also demonstrate that AUD results in decreased surfactant anti-microbial action.
Surfactant protein D has been documented to specifically bind to and aggregate bacteria for optimal
microbicidal action. We hypothesize that altered innate lung defense at the level of mucociliary clearance and
anti-microbial surfactants will negatively impact susceptibility and pathogenesis of bacterial pneumonia, placing
individuals with AUD particularly in harm’s way. Our assembled team of investigators include a VA Research
Career Scientist with 26 years’ experience in the impact of alcohol on lung injury and repair, a pulmonologist
whose expertise is on characterizing primary human lung clinical samples, experienced alcohol liver injury
researcher with extracellular vesicle expertise, a senior professor of pharmacy recognized internationally as a
zinc expert, and a junior investigator who is already an expert in alcohol-mediated gut dysbiosis and bacterial
infections. Our established expertise in mouse models of alcohol injury combined with our existing biobank of
human lung cells and tissues, we propose to address our hypothesis by identifying any differences in S.
pneumoniae infection responses due to a complex exposome model of alcohol, cigarette smoking, and zinc
deficiency. We will specifically identify in these groups any changes in cilia beat controlling clearance and the
role of reactive aldehydes generated by liver- and gut-derived extracellular vesicles. Such studies will be
performed for the first time in animal and cell models relevant to AUD. Defining the modalities of risk will also
empower clinicians to make informed preventive care de...

## Key facts

- **NIH application ID:** 10797027
- **Project number:** 5P50AA030407-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Todd A Wyatt
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $241,761
- **Award type:** 5
- **Project period:** 2023-02-28 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797027

## Citation

> US National Institutes of Health, RePORTER application 10797027, The Exposome and Lung Bacterial Infection: Role of Liver and Gut-derived Extracellular Vesicles (5P50AA030407-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10797027. Licensed CC0.

---

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