Date Published: February 1, 2019
Publisher: Public Library of Science
Author(s): Vanessa Stadlbauer, Angela Horvath, Irina Komarova, Bianca Schmerboeck, Nicole Feldbacher, Sonja Wurm, Ingeborg Klymiuk, Marija Durdevic, Florian Rainer, Andreas Blesl, Sarah Stryeck, Tobias Madl, Philipp Stiegler, Bettina Leber, Helge Bruns.
Alcohol binge drinking is a dangerous drinking habit, associated with neurological problems and inflammation. The impact of a single alcohol binge on innate immunity, gut barrier and gut microbiome was studied. In this cohort study 15 healthy volunteers received 2 ml vodka 40% v/v ethanol/kg body weight. Neutrophil function was studied by flow cytometry; markers of gut permeability and inflammation (lactulose/mannitol/sucrose test, zonulin, calprotectin, diamino-oxidase) were studied with NMR spectroscopy and enzyme-linked immunosorbent assay in urine, stool and serum respectively. Bacterial products in serum were quantified using different reporter cell lines. Gut microbiome composition was studied by 16S rDNA sequencing and bioinformatics analysis. After a single alcohol binge, neutrophils were transiently primed and the response to E.coli stimulation with reactive oxygen species (ROS) production was transiently increased, on the other hand the percentage of neutrophils that did not perform phagocytosis increased. No changes in gut permeability, inflammatory biomarker, bacterial translocation and microbiome composition could be detected up to 4 hours after a single alcohol binge or on the next day. A single alcohol binge in young, healthy volunteers transiently impacts on neutrophil function. Although the exact biological consequence of this finding is not clear yet, we believe that this strengthens the importance to avoid any alcohol binge drinking, even in young, otherwise healthy persons.
Alcohol binge drinking, defined as 5 or more drinks for men and 4 or more drinks for women within 2 hours, 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 behavioral and neurological consequences of binge drinking are well characterized [2–4]. Less is known about the systemic effects on the intestine as the first organ in contact with alcohol and on the consequences on inflammation and immune function. Chronic alcohol intake can lead to increased gut permeability, bacterial translocation and alterations in the gut microbiome in animal models [5–7]. Recently bacterial translocation has been shown in healthy volunteers after a single alcohol binge  and in frequent binge drinkers . On immune cells, alcohol intake seems to have dichotomous effects. On the one hand alcohol-induced liver injury is driven by pro-inflammatory reactions, whereas in the long-term, immunosuppressive and anti-inflammatory effects have been described . These immune effects, via Toll-like receptors, may be driven by endotoxin or other bacterial products that are translocated to the circulation via a defective gut barrier . It is so far unknown what effects a single alcohol binge has on gut microbiome, gut barrier, bacterial translocation and innate immunity. We therefore aimed to study whether a single alcohol binge with 2 ml of vodka 40% v/v ethanol/kg body weight impairs gut barrier and gut microbiome composition, increases bacterial translocation and inflammation and impacts on neutrophil dysfunction.
15 volunteers participated in the study and all individuals completed the study (Fig 1). Baseline characteristics are given in Table 1. None of the volunteers had any evidence of acute or chronic diseases at the time of the study and no drug (prescription or non-perceptional) intake was reported. Alcohol binge did not cause any severe adverse events. Smoking status did not have any impact on any parameters at baseline.
Our study shows that one single alcohol binge in young, healthy volunteers without dangerous alcohol consumption habits impacts on innate immune function, even though it has no detectable effect on gut permeability, bacterial translocation and microbiome composition.
Taken together, a single alcohol binge in young, healthy persons without any dangerous alcohol drinking behavior, impacts on neutrophil burst and phagocytic function, but gut microbiome composition and function and the gut barrier function remains unaltered. Innate immune dysfunction during long-term alcohol misuse therefore may not only be caused by bacterial products leading to “immune paralysis”  but also directly through ethanol effect on neutrophil granulocytes or through other indirect effects not related to the gut barrier.