Investigating the Rescue Potential of Fecal Microbiota Transplants in Anorexia Nervosa using Antibiotic-treated Mice in a Split Group Cross-Over Study

Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from AN patients on food intake, body weight, behavior, and gut microbiota in antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received FMT from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a healthy donor. The first FMT, from AN donors, resulted in lower food intake in mice without affecting body weight. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Gut microbiota analysis showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a healthy donor potentially offering FMT as a supportive treatment for AN. ### Competing Interest Statement SM declares no conflict of interest. TH declares no conflict of interest. LK declares no conflict of interest. LFZ declares no conflict of interest. DBS declares that he has collaborated with pharmaceutical industry and received funding from this source as described on https://research.ku.dk/search/result/?pure=en/persons/114880 CMJM declares no conflict of interest. AKH declares that he has collaborated with pharmaceutical industry and received funding from this source, as well as he is the owner of a diabetes related patent as described on https://ivh.ku.dk/english/employees/?pure=en/persons/107126. MS declares no conflict of interest. KKB declares no conflict of interest.