Anorexia nervosa (AN) is characterised by the restriction of energy intake in relation to energy needs and a significantly lowered body weight than normally expected, coupled with an intense fear of gaining weight. Treatment of AN is currently based on psychological and refeeding approaches, but their efficacy remains limited since 40% of patients after 10 years of medical care still present symptoms of AN. The intestine hosts a large community of microorganisms, called the “microbiota”, which live in symbiosis with the human host. The gut microbiota of a healthy human is dominated by bacteria from two phyla: Firmicutes and, majorly, Bacteroidetes. However, the proportion in their representation differs on an individual basis and depends on many external factors including medical treatment, geographical location and hereditary, immunological and lifestyle factors. Drastic changes in dietary intake may profoundly impact the composition of the gut microbiota, and the resulting dysbiosis may play a part in the onset and/or maintenance of comorbidities associated with AN, such as gastrointestinal disorders, anxiety and depression, as well as appetite dysregulation. Furthermore, studies have reported the presence of atypical intestinal microbial composition in patients with AN compared with healthy normal-weight controls. This review addresses the current knowledge about the role of the gut microbiota in the pathogenesis and treatment of AN. The review also focuses on the bidirectional interaction between the gastrointestinal tract and the central nervous system (microbiota–gut–brain axis), considering the potential use of the gut microbiota manipulation in the prevention and treatment of AN.

Recent advances highlight that nutrient receptors (such as T1R1/T1R3 heterodimer, Ca sensing receptor and GPR93 for amino acids and protein, GPR40, GPR41, GPR43 and GPR120 for fatty acids, T1R2/T1R3 heterodimer for monosaccharides) are expressed in the apical face of the gut and sense nutrients in the lumen. They transduce signals for the regulation of nutrient transporter expressions in the apical face. Interestingly, they are also localised in enteroendocrine cells (EEC) and mainly exert a direct control on the secretion in the lamina propria of gastro-intestinal peptides such as cholecystokinin, glucagon-like peptide-1 and peptide YY in response to energy nutrient transit and absorption in the gut. This informs central nuclei involved in the control of feeding such as the hypothalamus and nucleus of the solitary tract of the availability of these nutrients and thus triggers adaptive responses to maintain energy homoeostasis. These nutrient receptors then have a prominent position since they manage nutrient absorption and are principally the generator of the first signal of satiation mechanisms mainly transmitted to the brain by vagal afferents. Moreover, tastants are also able to elicit gut peptides secretion via chemosensory receptors expressed in EEC. Targeting these nutrient and tastant receptors in EEC may thus be helpful to promote satiation and so to fight overfeeding and its consequences.