Dysregulation of the Microbiota–Gut–Brain Axis Drives Binge Eating Behavior Independent of Obesity
Abstract Background 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 imbalanced gut microbiota composition, therefore questioning the role of obesity in binge eating. However, recent investigations suggest that repeated intake of highly palatable food is sufficient to promote changes in eating behavior, before obesity onset.  Results 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 such 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, including potentially harmful species such as Escherichia, Streptococcus, and certain Clostridium spp., alongside sugar-fermenters like Bifidobacterium and Roseburia. We further report that gut microbial alpha diversity (Shannon index) does not only correlate with hyperphagic behavior but with disrupted hypothalamic leptin sensitivity as well.  Conclusions 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.