Dysregulated microbiota-gut brain axis induced by intermittent access to palatable food is associated with binge eating regardless of obesity development

Changes in dietary habits and increased consumption of high fat/high sugar content have contributed to an increased prevalence of obesity in the general population, while recurrent consumption of highly processed food leads to compulsive overeating in a smaller number of subjects. Obesity has long been associated with peripheral inflammation, loss of sensitivity to appetite controlling hormones and an imbalanced gut microbiota composition, therefore interrogating the role of obesity in the worsening of binge eating behavior. However, recent investigations suggest that repeated intake of highly palatable food is sufficient to promote changes in eating behavior, before obesity onset. In this study, we demonstrate that intermittent access to high fat/high sugar food results in binge-type eating behavior, neuroinflammation and loss of sensitivity for leptin signaling in the hypothalamus of non-obese female rats. Our data also indicate that a sporadic feeding with cheesecake is sufficient to increase the gut microbial diversity, favoring the overrepresentation of taxa that can exploit high sugar and fat availability. We further show that gut microbial alpha diversity does not only correlate with hyperphagic behavior but also with disrupted hypothalamic leptin sensitivity. Overall, our observations demonstrate that intestinal microbiota alterations and hypothalamic neuroinflammation precede obesity in a rat model of binge eating. This suggests that early interventions aiming at reducing central inflammation and/or rebalancing the gut microbiota composition could help to prevent or reduce compulsive overeating.