Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals

Abstract

Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to men, women had higher blood alcohol and circulating endotoxin levels. In addition, alcohol binge caused a prolonged increase in acute phase protein levels in the systemic circulation. The biological significance of the in vivo endotoxin elevation was underscored by increased levels of inflammatory cytokines, TNFα and IL-6, and chemokine, MCP-1, measured in total blood after in vitro lipopolysaccharide stimulation. Our findings indicate that even a single alcohol binge results in increased serum endotoxin levels likely due to translocation of gut bacterial products and disturbs innate immune responses that can contribute to the deleterious effects of binge drinking.

Figure 1. Induction of blood alcohol content and serum endotoxin after an acute binge drink in healthy humans.

A–D. Serum alcohol (A and B, n = 8) and endotoxin (C and D, n = 16) levels were measured as described in methods. The data for serum alcohol (B) and endotoxin (D) was presented separately for men and women. Data is presented as mean ± S.E., and depending upon the data distribution, statistical analysis was performed either with Mann-Whitney U test or Student's two-tailed test. *p<0.05. *represents comparison between baseline and treatment groups. # represents comparison between men and women.

Figure 2. Induction of acute phase proteins after an acute binge drink in healthy humans.

A–B. Serum LBP (A, n = 21) and serum sCD14 (B, n = 21) were measured as described in methods. Data is presented as mean ± S.E., and depending upon the data distribution, statistical analysis was performed either with Mann-Whitney U test or Student's two-tailed test. *p<0.05.

Figure 3. Induction of bacterial DNA after an acute binge drink in healthy humans.

DNA was isolated from the serum (n = 22) using QIAamp mini kit (Qiagen) and 16S rDNA was amplified using 16S universal primers. The fold change was calculated compared to baseline samples of the same individual. Data is presented as mean ± S.E. *p<0.05.

Figure 4. Physiological dose of LPS induces immune response in whole blood plasma of normal individuals.

The amount of TNFα, IL-6 and MCP1 was measured by ELISA from the whole blood plasma collected after 18 h of LPS (100 pg/ml) treatment (n = 4). Data is presented as mean ± S.E. *p<0.05.