# Intestinal bacteria and epithelial barrier disruption after alcohol and burn injury

> **NIH NIH R01** · LOYOLA UNIVERSITY CHICAGO · 2021 · $409,597

## Abstract

Alcohol-related traumatic and burn injuries remain a considerable health and economic burden to the American
society. Studies have shown that patients who are intoxicated at the time of injury are more susceptible to
infection and exhibit significantly higher morbidity and mortality compared to burn patients who are not
intoxicated at the time of injury. Yet, the mechanism by which alcohol (ethanol) enhances post burn
pathogenesis remains largely unclear. Gut barrier dysfunction is frequently associated with ethanol exposure
and major injury. We have shown that the ethanol intoxication combined with moderate burn injury causes
intestinal tissue damage, leakiness, and a significant increase in bacterial translocation within 24 hours after
injury. We further observed a decrease in the expression of microRNA (miR-7a and miR-150) and microRNA
biogenesis components Drosha and Argonaute-2 in intestinal epithelial cells (IEC) one day following alcohol
and burn injury. Moreover, ethanol combined with burn injury increases bacterial load (Enterobacteriaceae) in
the small intestine. Such an increase in Enterobacteriaceae may disrupt the bacteria/host interactions and
potentiate the inflammatory response by activating pattern recognition receptors (PRR) expressed on IECs
leading to intestine tissue damage and leakiness following ethanol and burn injury. Our hypothesis is that
accumulation of Gram-negative bacteria (i.e. Enterobacteriaceae) in intestine following ethanol and burn injury
perturbs gut microbiota-epithelial interactions, which become exacerbated by altered microRNA homeostasis,
thus, culminating in gut inflammation and barrier disruption. The hypothesis will be tested in 3 Aims in a well-established
mouse model of ethanol intoxication and burn injury. Studies in Aim 1 are designed to delineate
the mechanism by which ethanol and burn induced changes in intestinal bacteria influence intestine barrier
integrity following injury. Aim 2 will determine whether changes in gut bacteria alone or in combination with an
increase in HIF-1α influence the expression of miR-150 and miR-7a and whether restoration of miR-150 and/or
miR-7a in intestinal epithelial cells following alcohol and burn injury reduces gut inflammation and improves
barrier integrity. Furthermore studies in Aim 3 will determine whether treatment of animals with probiotics reestablishes
gut microbiota and intestine barrier integrity following alcohol and burn injury. The findings from
these studies will reveal a novel role for gut microbiota in gut leakiness following ethanol intoxication and burn
injury and in turn may help in developing new therapeutic strategies for patients suffering from a combined
insult of ethanol and burn injury.

## Key facts

- **NIH application ID:** 10180982
- **Project number:** 5R01GM128242-04
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Mashkoor A Choudhry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $409,597
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180982

## Citation

> US National Institutes of Health, RePORTER application 10180982, Intestinal bacteria and epithelial barrier disruption after alcohol and burn injury (5R01GM128242-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10180982. Licensed CC0.

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