Alcohol and Innate Immunity

The Effects of Binge Drinking on Innate Host Defence Mechanisms

Alcohol leads to a leaky gut and translocation of bacterial products. This may lead to inflammation and immune dysfunction as well as the typical hangover symptoms.

Study Overview

• Status: Completed
• Conditions: Binge Drinking
• Intervention / Treatment: Other: Alcohol; Other: Fructose; Other: Glucose; Other: vehicle

Detailed Description

Alcohol binge drinking, defined as 5 or more drinks for men and 4 or more drinks for women at one time, is the most frequent form of alcohol consumption worldwide, especially in younger people. This drinking pattern is popular and leads to increased mortality and morbidity. Therefore binge drinking is a major public health issue. The behavioural and neurological consequences of binge drinking are well characterized.

Less is known about the systemic effects on the gut as the first organ in contact with alcohol. Chronic alcohol intake can lead to increased gut permeability, bacterial translocation and alterations in the gut microbiome in animal models. Recently bacterial translocation has been shown in healthy volunteers after a single alcohol binge. On immune cells, acute alcohol intake seems to have dichotomous effects. On the one hand immunosuppressive and anti-inflammatory effects have been described, however, alcohol induced liver injury is driven by pro-inflammatory reactions. These immune effects seem to be driven by endotoxin or other bacterial products via Toll-like receptors that are translocated to the circulation via a defective gut barrier. Immune effects of alcohol have also been linked to hangover symptoms after an alcohol binge.

Furthermore there is evidence that endotoxemia might also contributes to alcohol dependence by promoting prolonged and increased voluntary alcohol intake in mice. On the other hand mutant mice lacking important genes for immune responses exhibit decreased alcohol consumption. This indicates that immune signaling promotes alcohol consumption. Therefore it is tempting to speculate that increased gut permeability leading to increased bacterial translocation after an acute alcohol binge could promote the desire for further alcohol consumption.

The investigators aim to test in this pilot trial whether one alcohol binge damages gut barrier function, increases bacterial translocation and causes innate immune dysfunction. Furthermore the effect of glucose and fructose will be studied too.

• Study Type: Observational
• Enrollment (Actual): 46

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Department of Internal Medicine, Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Healthy volunteers selected from a database

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the study.
• Age above 18 years
• Willingness to abstain from alcohol 48h prior to the study visits

Exclusion Criteria:

• Alcohol abuse .Alcohol Use Disorders Identification Test ≥ 8 in men or ≥ 7 in women or CAGE test ≥ 2 (both men and women)
• Elevated liver function test
• Any disease or medication that does not allow concomitant consumption of alcohol
• Women: pregnancy and lactation

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alcohol binge; Healthy volunteers receive 2ml vodka 40% per kg bodyweight as a binge	Other: Alcohol; every participant will drink vodka at a dose of 2ml/kg bodyweight
Fructose; 75 g Fructose orally	Other: Fructose; oral fructose tolerance test
Glucose; 75 g Glucose orally	Other: Glucose; oral Glucose tolerance test
Vehicle; 2ml tap water per kg body weight	Other: vehicle; control (water)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endotoxin assessed by percentage of endotoxin positive subjects	Endotoxin measured by a HEK-blue cell based assay	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gut permeability (zonulin in stool)	changes in gut permeability	4 hours
bacterial translocation (bacterial DNA in serum)	changes in bacterial translocation	4 hours
oxidative stress (advanced oxidation protein products)	changes in oxidative stress	4 hours
inflammation (neutrophil oxidative burst)	changes in inflammation	4 hours
neutrophil phagocytic capacity	changes in neutrophil function	4 hours
gut microbiome composition	changes in gut microbiome composition	4 hours
fibroblast growth factor 21 (FGF21)	changes in FGF21 serum levels	4 hours

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Vanessa Stadlbauer, MD, Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): February 22, 2019
• Study Completion (Actual): February 22, 2019

Study Registration Dates

• First Submitted: July 29, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Binge Drinking
• Other Study ID Numbers: Alcohol01