The microbiome and metabolome of patients with acute or severe and enduring anorexia nervosa influence gamma-aminobutyric acid (GABA) metabolism and microbial fermentation

Anorexia nervosa (AN), an eating disorder, is associated with marked changes in the microbiome and metabolic profile of those affected. In this study, we compared the diversity and composition of the gut microbiota and the differences in various parameters between 29 female patients with acute AN, 33 severe and enduring AN (SEAN), and 30 healthy controls. Both patient groups differed in the assessment of eating behaviors, depression symptoms, stressful events in adulthood, and the use of antidepressants. The SEAN group showed elevated markers of gut damage and the greatest inter-individual variation in the gut microbiome. Certain bacterial taxa, such as Faecalibacterium , Fusicatenbacter , Lachnospiraceae, and CAG-56, were less abundant in the patients' microbiomes, while Erysipelatoclostridium and UBA1819 were more abundant, but with no difference between patient groups. Functional prediction of the microbiome revealed differences in metabolic pathways, particularly in amino acid metabolism and oxidative stress responses, which were more pronounced in patients with SEAN. Certain bacteria such as Christensenellaceae, Ruminococcaceae, and Escherichia-Shigella negatively affect GABA metabolism, as evidenced by the lower serum and fecal concentrations in both patient groups compared to healthy women. Members of the Christensenellaceae affect microbial fermentation, resulting in significant differences in acetic, propionic, and butyric acid levels in stool and serum samples from AN patients. These findings highlight the complex interplay between the gut microbiota and metabolic changes in AN patients and provide insights into potential microbial biomarkers and therapeutic targets for this disease.