Weight Cycling Deregulates Eating Behavior in Mice via the Induction of Durable Gut Dysbiosis

Abstract Background & Aims: Alternating periods of excessive and restrained eating results in weight cycling (‘yo‐yo’ effect), a suspected risk factor for eating behavior dysregulation such as binge eating. The hypothesis that recurrent diet alternation alters hedonic feeding regulation by changing either or both intestinal microbiota and brain neuronal and glial regulation in mouse is tested. Methods : C57BL/6 mice undergo 3 cycles of 1 week of western diet (WD) separated by 2 weeks of chow diet (CYCL group) or remain under chow diet (CTRL group). Results : CYCL mice exhibit weight cycling, with enhanced weight gain upon each WD feeding phase and increased energy intake specifically during the first hours following WD re‐introduction, reminiscent of binge‐eating episodes. Expression of reward‐related genes in the striatum and thickness of the astro‐glial barrier in the brain stem is enhanced in CYCL mice. Diet alternation induces caecal dysbiosis in CYCL mice. Gut microbiota transfer from CYCL mice to naive recipient mice recapitulates the altered eating behavior upon WD exposure. Conclusions : Alternation between high‐energy and standard diets is established to durably remodel the gut microbiota and the brain toward a profile associated with an increase in hedonic appetite and that this microbiota signature affects hedonic feeding regulation.