# Impact of Peripheral Circadian Misalignment on Resiliency of Intestinal Barrier Function to Alcohol

> **NIH NIH F31** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $46,036

## Abstract

Project Abstract
 Only 20-30% of heavy alcoholics develop alcohol-induced intestinal hyperpermeability and alcoholic liver
disease (ALD). Thus, emphasizing other cofactors that play a critical role is necessary to better
understand mechanisms behind pathogenesis. Recent years have seen an increased prevalence of circadian
rhythm disruption that contributes to human disease pathogenesis such as colonic hyperpermeability.
However, the role of peripheral circadian misalignment in barrier homeostasis of t he gastrointestinal tract (GIT)
is incompletely understood. Our focus is on the peripheral circadian clock in relation to alcohol consumption.
Peripheral circadian disruption can occur by eating close to the body’s biological rest period. This ‘wrong-time
eating’ (WTE) can cause changes in the intestinal microbiota and their metabolites, which may mediate
intestinal gut leakiness to alcohol. Thus, we will test the overall hypothesis that peripheral circadian disruption
will decrease resiliency of the intestinal barrier function to alcohol, mediated through microbial metabolites .
Aim 1: Establish that peripheral circadian disruption through WTE decreases resiliency of the colon to
alcohol. We will disrupt peripheral circadian rhythms in PERIOD2 luciferase (PER2::Luc) reporter BL/6 mouse
model and assess the effect of alcohol consumption on intestinal permeability and intestinal barrier function
Aim 2: Demonstrate that bacterial metabolites impact peripheral circadian rhythms and mediate
decreased resiliency of colonic barrier function. We will demonstrate that bacterial metabolites can affect
circadian rhythms as well as mediate changes in intestinal barrier function through colonic PER2::LUC
organoids. In this proposed research, I will expand knowledge regarding the impact of peripheral circadian
misalignment on intestinal resiliency to alcohol. Additionally, I will investigate the effect of bacterial metabolites
from peripherally circadian disrupted PER2::LUC mice. The proposed work will elucidate how wrong -time
eating makes the gut more susceptible to injury by alcohol by mechanisms related to microbial dysbiosis and
bacterial products. Successful completion of this research would greatly increase our understanding of a key
co-factor in alcohol induced barrier disfunction. Ultimately, the establishment of colonic peripheral circadian
misalignment in ALD and identifying the microbial metabolites associated with this phenotype will lead to the
development of microbial and circadian related interventions and identify therapeutic targets to mitigate
alcohol-induced damage. This proposal will enhance the trainee’s ability to conceptualize, develop, execute,
and evaluate meaningful research questions with increasing independence and will help her develop into a
productive, leading independent research scientist. The research project and ca reer development will be
guided by an outstanding team of sponsors and the dissertation committee who are excepti...

## Key facts

- **NIH application ID:** 10315546
- **Project number:** 1F31AA029631-01
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Laura Tran
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315546

## Citation

> US National Institutes of Health, RePORTER application 10315546, Impact of Peripheral Circadian Misalignment on Resiliency of Intestinal Barrier Function to Alcohol (1F31AA029631-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10315546. Licensed CC0.

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