509. INVOLVEMENT OF THE GUT-BRAIN AXIS IN FOOD ADDICTION

Abstract Background Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and eating disorders. This alteration of eating control modifies gut microbiota composition. However, the mechanisms underlying this behavioral disorder are largely unknown. Aims & Objectives We aimed to investigate the changes in miRNA expression and gut microbiota promoted by food addiction in male and female animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. Method We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify miRNA expression and gut microbiota signatures associated with vulnerability to this disorder, as well as the relationships between these epigenetic and gut microbiota changes. Results Male and female mice present several important differences in the behavioral manifestations of food addiction, which parallels the the differential manifestations of food addiction in men and women. Close similarities in miRNA signatures in the medial prefrontal cortex of our animal cohort and circulating miRNA levels in our human cohort were revealed. In addition, both animal and human cohorts showed similarities in the gut microbiota signatures linked to food addiction. Several miRNAs were revealed of potential interest in the development of this disorder. Indeed, tough decoy inhibition of miRNA-29c-3p and miRNA-665-3p enhanced food addiction vulnerability revealing their potential role as protective factors with regard to food addiction. The gut microbiota signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species Blautia wexlerae was observed in addicted humans and of Blautia genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour Blautia growth, led to increased relative abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of Blautia wexlerae as a beneficial microbe (see Figure). Close relationships were found in mice between the levels of miR-29c-3p in the medial prefrontal cortex and the abundance of Blautia in faeces. Discussion & Conclusions Male and female mice and humans present differential behavioral manifestations of food addiction. The elucidation of the involvement of these epigenetic and gut-brain mechanisms may lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related eating disorders. The understanding of the crosstalk between these epigenetic and gut microbiota changes may lead to the identification of specific mechanisms linking the changes in gut microbiota and the development of food addiction.