Gut microbiota contributions to anorexia nervosa pathogenesis: insights from the activity-based anorexia model

Anorexia nervosa (AN) is a severe eating disorder that profoundly affects quality of life. Despite increasing understanding of the neurobiological basis of the disease, many patients develop a chronic course of illness accompanied by a variety of physical and psychiatric comorbidities. To investigate the contribution of the gut microbiome to disease progression, we employed the activity-based anorexia (ABA) mouse model of AN. We performed fecal microbiota transplantation using samples from three donor groups: healthy controls, patients with acute AN, and patients with severe and enduring AN (SEAN). We continuously assessed changes in the gut microbiota and fecal metabolites (e.g., short-chain fatty acids, serotonin, and GABA) throughout the experiment, along with behavioral traits across the three groups of mice. Mice colonized with microbiota from acute AN patients exhibited reduced hunger signaling (via NPY, AgRP, MCH, and orexin), accompanied by decreased food intake. In contrast, mice transplanted with microbiota from SEAN patients showed appetite signaling and food consumption comparable to those colonized with microbiota from healthy controls but displayed significantly higher running activity relative to the other groups. However, the distinct microbiota did not affect the development of the ABA phenotype. Overall, our findings suggest that changes in the gut microbiome during disease development contribute to disease progression. Our results also indicate that restoration of a healthy gut microbiome is essential for complete recovery.