Role of gut microbiota in the biological and behavioral control of alcohol-dependence

Leclercq, Sophie [UCL] de Timary, Philippe [UCL] Neyrinck, Audrey M. [UCL] Cani, Patrice D. [UCL] Delzenne, Nathalie M. [UCL]

Background and objectives Alcohol dependence touches 5 – 7 % of the population in the developed countries. Alcohol-dependent (AD) subjects are characterized by an increase in intestinal permeability, enhanced blood lipopolysaccharides (LPS) levels and low-grade systemic inflammation. It has been shown that pro-inflammatory cytokines are correlated to psychological symptoms, such as depression and alcohol-craving. The effects of chronic alcohol consumption on gut microbiota have already been tested in animal models but data on humans are scarce. The aims of this study were to analyze the composition of the gut microbiota in AD subjects and to test the potential relationship between microbial composition and psychological symptoms. Methods 13 AD subjects, hospitalized for a 3-week detoxification program, and 15 healthy controls were included in this study. Intestinal permeability was measured using 51Cr-EDTA. Faecal microbiota composition was assessed using qPCR of 16S rDNA. Depression, anxiety, craving and emotional intelligence were assessed using psychological questionnaires. All patients were tested twice, at the onset and at the end of the alcohol-withdrawal. Results AD subjects showed a decrease in Lactobacillus, Bifidobacterium and Faecalibacterium praustnizii, compared with healthy controls whereas Bacteroides did not change between groups. A short term alcohol-abstinence allowed the recovery of Lactobacillus and Bifidobacterium to normal levels. Bifidobacterium and Faecalibacterium praustinizii were negatively correlated with intestinal permeability. Bifidobacterium were also negatively correlated with depression, anxiety, craving and positively correlated with emotional intelligence. Conclusion These data, obtained in humans, showed that heavy and chronic alcohol consumption modifies the composition of gut microbiota. These changes were associated with intestinal barrier dysfunction and, more interestingly, with psychological disorders, adding further evidence to the important role of “gut-brain axis” in the development of alcohol-dependence and a potent role of bacteria with anti-inflammatory properties in the management of psychological symptoms associated with alcohol dependence.