Are the Effects of Malnutrition on the Gut Microbiota-Brain Axis the Core Pathologies of Anorexia Nervosa?

Anorexia nervosa (AN) is a disabling, costly, and potentially deadly illness. Treatment failure and relapse after treatment are common. Several studies have indicated the involvement of the gut microbiota-brain (GMB) axis. This narrative review hypothesizes that AN is driven by malnutrition-induced alterations in the GMB axis in susceptible individuals. According to this hypothesis, initial weight loss can voluntarily occur through dieting or be caused by somatic or psychiatric diseases. Malnutrition-induced alterations in gut microbiota may increase the sensitivity to anxiety-inducing gastrointestinal hormones released during meals, one of which is cholecystokinin (CCK). The experimental injection of a high dose of its CCK-4 fragment in healthy individuals induces panic attacks, probably via the stimulation of CCK receptors in the brain. Such meal-related anxiety attacks may take part in developing the clinical picture of AN. Malnutrition may also cause increased effects from appetite-reducing hormones that also seem to have roles in AN development and maintenance. The scientific background, including clinical, microbiological, and biochemical factors, of AN is discussed. A novel model for AN development and maintenance in accordance with this hypothesis is presented. Suggestions for future research are also provided.