Microbiome-gut-brain interaction in Anorexia Nervosa (MiGBAN)

Innovation: By the current transnational collaboration it will be possible -for the first time - to systematically investigate the causal role of altered gut microbiota for the course and outcome of anorexia nervosa (AN) and identify potential new therapeutic options such as psychobiotics for this severe disorder. We investigate hypotheses: (1) Which microbiota are present in ill and recovered AN patients compared to HC? (2) How is the composition of microbiome related to weight gain, brain morphology, functional brain changes incl. the DA system and neuropsychological parameters in AN. (3) What is the immune response to changing microbiota in AN during starvation and weight rehabilitation process as well as by food supplementation or psychobiotics including antibodies reactive with hunger and satiety hormones and their roles in the brain DA system involved in feeding reward? In Vienna the effects of a multistrain psychobiotic (Lactobacillus casei W56 - combination) will be investigated via Placebo RCT in 60 adolescent in- and outpatients with AN for 6 months. The patients will be followed up until one year after admission. Primary outcome will be the change in BMI at one- year follow-up. Longitudinally, stool samples (for microbiome and proteome analyses) and serum samples (inflammation markers, antibodies and hormones) will be collected per patient and the same number of age- and sex-matched healthy controls (HC) between admission, discharge (short-term weight recovery), 6-months and 1 year follow-up. All probands will fill in clinical questionnaires at all time-points to assess eating disorder, depressive and anxiety symptoms. Neuropsychological tests will be administered to all patients and HCs at admission, discharge, and 1 year follow-up. In addition, 30 patients and 15 HCs each will undergo MRI-scanning (including volumetric MRI, fMRI, DTI, MRS on 3T-scanners). Results from microbiome, gut permeability, inflammation markers, hormone levels and brain imaging will be used to further disentangle the mechanisms of interaction involved in acute illness, during weight recovery and facilitate fundamentally new interventions. Expertise from preclinical and clinical backgrounds will be optimally combined in the current translational proposal by systematically paralleling animal and patient research. The project headed by Prof B Herpertz-Dahlmann (Aachen, Germany) will involve Prof J Baines (Kiel, Germany), Prof S Fetissov (Rouen, France), and Prof R Adan (Utrecht, NL). The Austrian team will be headed by Prof A Karwautz (Vienna, Austria) and involves Dr K Kollndorfer, Dr F Fischmeister, and Prof V Schöpf (Uni Graz) and Prof Sevecke (MedUni Innsbruck).