Role of intestinal permeability and inflammation on the biological and behavioral control of alcohol-dependent subjects

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

Aims: Alcohol-dependence is commonly investigated in relation to modification of various neurotransmitters in brain. Our hypothesis is that the development of alcohol dependence could also involve more peripheral mechanisms and especially gut-brain interactions. Our first goal was to test whether intestinal permeability, lipopolysaccharides (LPS) and inflammatory cytokines are increased in alcohol-dependent subjects and recover after withdrawal. To explore the possible role of gut-brain axis in alcoholism, our second goal was to test correlations between the biological and the behavioral variables that are known to play a central role in alcohol-dependence, such as depression, anxiety, alcohol craving and selective attention. Methods: 40 alcohol-dependent-subjects hospitalized for detoxification program were tested both at onset (T1) and end (T2) of withdrawal and compared for biological and behavioral markers with a control group. Participants were evaluated for gut permeability, LPS, systemic inflammation (TNFα, IL-6, IL-10, hsCRP) and stress (Cortisol) and for depression (BDI), anxiety (STAI), alcohol craving (OCDS) and selective attention (BAWL). Results: Intestinal permeability and LPS that were largely increased in alcohol-dependent subjects at T1 recovered completely at T2. A low-grade inflammation was observed at T1and recovered partially after withdrawal in parallel with the psychological variables. We found that pro-inflammatory markers were positively correlated with depression and craving. The anti-inflammatory cytokine IL-10 was negatively correlated with depression and craving. Conclusion: Leaky gut-induced inflammation is correlated to emotions and craving for alcohol. We can therefore consider that gut-brain axis may play a significant role in the development of alcoholic pathology. IL-10 could be a protective factor in relation to emotional disturbances and relapse probability. Moreover, recent animal and human studies have shown that chronic alcohol consumption altered gut microbiota. An interesting perspective would be to test pro- or prebiotics that are known to improve the composition of gut microbiota and therefore restore the gut barrier to reduce inflammation, depression and craving to help patients to remain abstinent.