Microbiota-gut-brain axis drives overeating disorders.

Overeating disorders (ODs), usually stemming from dieting history and stress, remain a pervasive issue in contemporary society, with the pathological mechanisms largely unresolved. Here, we show that alterations in intestinal microbiota are responsible for the excessive intake of palatable foods in OD mice and patients with bulimia nervosa (BN). Stress combined with a history of dieting causes significant changes in the microbiota and the intestinal metabolism, which disinhibit the vagus nerve terminals in the gut and thereby lead to a subsequent hyperactivation of the gut-brain axis passing through the vagus, the solitary tract nucleus, and the paraventricular nucleus of the thalamus. The transplantation of a probiotic Faecalibacterium prausnitzii or dietary supplement of key metabolites restores the activity of the gut-to-brain pathway and thereby alleviates the OD symptoms. Thus, our study delineates how the microbiota-gut-brain axis mediates energy balance, unveils the underlying pathogenesis of the OD, and provides potential therapeutic strategies.