MULTIMODAL CHARACTERIZATION OF BINGE EATING DISORDER IN WILD-TYPE MICE: BEHAVIORAL, PROTEOMIC AND GUT MICROBIOTA (16S RRNA) ANALYSES

Background: Binge eating disorder (BED) is an eating disorder characterized by recurrent episodes of excessive food intake and high comorbidity with psychiatric conditions. Its prevalence increased and current pharmacological treatments show limited efficacy, highlighting the need to further investigate its neurobiological basis. The aim of this study was to characterize anxiety- and compulsive-like behaviors, evaluate molecular alterations at the hypothalamic level and in the gut microbiota, and assess the influence of environmental factors on BED predisposition.
Methods: Female wild-type C57BL/6J mice (30–40 days old) were assigned to three groups: control without exposure (Control S/E), control with continuous exposure to palatable food (Control E/C), and intermittent exposure (Binge). For 30 days, the Binge group had access to palatable food for 2-hours on alternate days. Anxiety- and compulsive-like behaviors were assessed using standardized behavioral tests. Hypothalami from the Control E/C and Binge groups were analyzed by LC-MS/MS-based proteomics, and gut microbiota composition was evaluated by 16S-rRNA gene sequencing. In addition, an unpredictable chronic mild stress (UCMS) protocol was applied in combination with the binge paradigm.
Results: The Binge group showed increased palatable food intake and a significant increase in anxiety- and compulsive-like behaviors. Proteomic analysis identified 173 differentially expressed proteins, mainly associated with GABAergic-signaling, inflammatory pathways, and others. Microbiota analysis revealed significant differences in relative abundance as well as alpha and beta diversity. Exposure to UCMS further potentiated compulsive-like behaviors in both Control E/C and Binge groups.
Conclusion: Together, these findings suggest that intermittent exposure and environmental stress contribute to a neurobiological predisposition to BED.