FTO deficiency reduces anxiety- and depression-like behaviors in mice via alterations in gut microbiota

Epidemiological evidence has identified robust associations between obesity and depression, demonstrating that obesity is a risk factor for future common mental disorders. In the present study, we investigated the role of the obesity-susceptibility gene FTO in the modulation of mood disorder. We show that deletion of the FTO reduces anxiety-like and depression-like behaviors in novel condition and increases abundance of Lactobacillus in gut microbiota. We report that FTO-deficient mice present less susceptibility to chronic unpredictable mild stress, highlighting the essential role of FTO in pathogenesis of mood disorders. Our results indicate that these alterations in behaviors are mediated by a shift in gut microbiota composition that can partially narrow by antibiotics. Together, our findings demonstrated that FTO deficiency to reduce anxiety and depression-like behaviors by altering the gut microbiota. These findings also provide a starting point in understanding the biological mechanism involved in the association between obesity and depression.