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

> **NIH NIH R01** · LOYOLA UNIVERSITY CHICAGO · 2020 · $71,487

## Abstract

Project Summary/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. Similar to clinical findings, studies performed in experimental conditions also
suggest that ethanol intoxication at the time of burn injury decreases host resistance to infectious
complications. Yet, the mechanism by which 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 found that
ethanol combined with burn injury increases bacterial load (primarily Gram-negative bacteria) in the gut. Such
a shift in gut microbiota may perturb bacteria/host interactions to produce a microenvironment conducive for
neutrophil accumulation and activation, leading to tissue damage and gut leakiness following ethanol and burn
injury. Our hypothesis is that accumulation of intestinal Gram-negative (i.e. enterobactericeae) bacteria
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
Aim1 are to delineate the mechanism by which ethanol and burn induced changes in gut bacteria influence gut
barrier integrity following injury. We will use TLR-2, TLR-4, Nod-1 and/or Nod-2 deficient mice to identify the
key PRR by which intestine epithelial cells detect Gram-negative bacteria and/or their products. Aim 2 will
determine whether restoration of microRNA biogenesis or miR-150 in intestine epithelial cells following alcohol
and burn injury reduces gut inflammation and prevents barrier disruption. Furthremore studies in Aim3 will
determine whether treatment of animals with probiotics re-establishes gut microbiota and gut barrier following
burn injury. The findings from these studies will reveal a novel role for gut microbiota in altered gut barrier
function 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 intoxication and burn injury.

## Key facts

- **NIH application ID:** 10134763
- **Project number:** 3R01GM128242-02S1
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Mashkoor A Choudhry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,487
- **Award type:** 3
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134763

## Citation

> US National Institutes of Health, RePORTER application 10134763, Intestinal bacteria and epithelial barrier disruption after alcohol and burn injury (3R01GM128242-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10134763. Licensed CC0.

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