Alcohol and Innate Immunity

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Effects of Binge Drinking on Innate Host Defence Mechanisms

Conditions
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Binge Drinking

Intervention / Treatment
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* Other: Alcohol
* Other: Glucose
* Other: Fructose
* Other: vehicle


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 |