Evidence map›Paper›PMID 34556145›Full record

ArticleImmunity & ageing : I & A2021

A novel murine model of multi-day moderate ethanol exposure reveals increased intestinal dysfunction and liver inflammation with age.

Rachel H McMahan, Kevin M Najarro, Juliet E Mullen, Madison T Paul, David J Orlicky, Holly J Hulsebus, Elizabeth J Kovacs

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Immunity & ageing : I & A, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Rachel H McMahanDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Alcohol Research Program, University of Colorado Denver, Anschutz Medical Campus, 12700 East 19th Ave, RC2, Mail Stop #8620, CO, 80045, Aurora, USA. Rachel.McMahan@CUAnschutz.edu.
Kevin M NajarroDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Alcohol Research Program, University of Colorado Denver, Anschutz Medical Campus, 12700 East 19th Ave, RC2, Mail Stop #8620, CO, 80045, Aurora, USA.
Juliet E MullenDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Alcohol Research Program, University of Colorado Denver, Anschutz Medical Campus, 12700 East 19th Ave, RC2, Mail Stop #8620, CO, 80045, Aurora, USA.
Madison T PaulDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Alcohol Research Program, University of Colorado Denver, Anschutz Medical Campus, 12700 East 19th Ave, RC2, Mail Stop #8620, CO, 80045, Aurora, USA.
David J OrlickyDepartment of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Holly J HulsebusDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Alcohol Research Program, University of Colorado Denver, Anschutz Medical Campus, 12700 East 19th Ave, RC2, Mail Stop #8620, CO, 80045, Aurora, USA.
Elizabeth J KovacsDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Alcohol Research Program, University of Colorado Denver, Anschutz Medical Campus, 12700 East 19th Ave, RC2, Mail Stop #8620, CO, 80045, Aurora, USA.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · US

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Edward L Melanson · 1995 to 2026
$32.6M
Aging, macrophage mediators, and burn trauma: SupplementR01AG018859 · NIA · UNIVERSITY OF COLORADO DENVER · PI KOVACS, ELIZABETH J. · 2001 to 2024
$7.6M
Alcohol and Burn Trauma: Multi-organ Inflammatory ResponsesR35GM131831 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ELIZABETH J. KOVACS · 2019 to 2026
$3.5M
Alcohol and Lung Immunity in the AgedR21AA026295 · NIAAA · UNIVERSITY OF COLORADO DENVER · PI KOVACS, ELIZABETH J. · 2018 to 2019
$408k
Ethanol effects on pulmonary innate immunity in a murine model of agingF31AA027687 · NIAAA · UNIVERSITY OF COLORADO DENVER · PI HULSEBUS, HOLLY J · 2019 to 2021
$101k
Multi-organ Inflammatory Responses after Burn TraumaI01BX004335 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI KOVACS, ELIZABETH J. · 2019 to 2023
–
BLRD VA I01 BX004335NIAAA NIH HHS F31 AA027687NIAAA NIH HHS F31AA027687NIAAA NIH HHS R21 AA026295NIA NIH HHS R01 AG018859NIDDK NIH HHS P30 DK048520NIGMS NIH HHS R35 GM131831U.S. Department of Veterans Affairs 1 I01 BX004335
6 · The paper itself

Abstract

backgroundThere are currently > 600 million people over the age of 65 globally and this number is expected to double by the year 2050. Alcohol use among this population is on the rise, which is concerning as aging is associated with increased risk for a number of chronic illnesses. As most studies investigating the effects of alcohol have focused on young/middle-aged populations, there is a dearth of information regarding the consequences of alcohol use in older consumers. In addition, most murine ethanol models have concentrated on exposure to very high levels of ethanol, while the vast majority of elderly drinkers do not consume alcohol in excess; instead, they drink on average 2 alcoholic beverages a day, 3-4 days a week.

methodsWe designed a murine model of aging and moderate ethanol consumption to determine if the deleterious effects of alcohol on the gut-liver axis are exacerbated in aged, relative to younger, animals. Aged and young mice were exposed to a multi-day moderate exposure ethanol regimen for 4 weeks and changes in gut permeability along with intestinal tight junction protein and antimicrobial peptide gene expression were measured. In addition, hepatic inflammation was assessed by histological analysis, inflammatory gene expression and flow cytometric analysis of inflammatory infiltrate.

resultsOur results reveal that in aged, but not young mice, moderate ethanol exposure yielded significantly worsened intestinal permeability, including increased bacterial translocation from the gut, elevated serum iFABP and leakage of FITC-dextran from the gut. Interestingly, moderate ethanol exposure in young animals led to gut protective transcriptional changes in the ileum while this protective response was blunted in aged mice. Finally, moderate ethanol exposure in aged mice also resulted in marked inflammatory changes in the liver.

conclusionsThese results demonstrate that aged mice are more susceptible to ethanol-induced gut barrier dysfunction and liver inflammation, even at moderate doses of ethanol. This increased vulnerability to ethanol's gastrointestinal effects has important implications for alcohol use in the aging population. Future studies will explore whether improving intestinal barrier function can reverse these age-related changes.

Indexed as

AgingAlcoholAntimicrobial peptideGut barrierLiver

Identifiers

PMID34556145
PMCPMC8459518
OpenAlexW3200424716

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.