The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial

Trials, vol. 23, pp. 545

Abstract

BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN. METHODS: This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology. DISCUSSION: Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017130 . Registered on 12 November 2019.

Authors 20

1. Lara Keller corresponding Aachen Department of Child and Adolescent Psychiatry

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany. lkeller@ukaachen.de

   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany

2. Astrid Dempfle

   Christian-Albrechts-Universität zu Kiel

   Affiliation as printed

   Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany

3. Brigitte Dahmen Aachen Department of Child and Adolescent Psychiatry

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany

4. Samira Schreiber Aachen Department of Child and Adolescent Psychiatry

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany

5. Roger A.H. Adan

   University Medical Center Utrecht

   Affiliation as printed

   Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands

6. Nadia Andrea Andreani

   Max Planck Institute for Evolutionary Biology

   Affiliation as printed

   Max Planck Institute for Evolutionary Biology, Plön, Germany

7. Unna Nora Danner

   Utrecht University · Altrecht GGZ

   Affiliation as printed

   Altrecht Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, The Netherlands

   Department of Clinical Psychology, Utrecht University, Utrecht, Netherlands

8. Albrecht Eisert Aachen Institute of Clinical Pharmacology

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Institute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany

9. Sergueı̈ O. Fetissov

   Inserm · Université de Rouen Normandie

   Affiliation as printed

   INSERM UMR-1239, University of Rouen Normandy, Rouen, France

10. Florian Ph. S. Fischmeister

    Medical University of Vienna · University of Graz · BioTechMed-Graz

    Affiliation as printed

    BioTechMed, Graz, Austria

    Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria

    Institute of Psychology, University of Graz, Graz, Austria

11. Andreas F. K. Karwautz

    Medical University of Vienna

    Affiliation as printed

    Eating Disorders Unit at the Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria

12. Kerstin Konrad Aachen Department of Child and Adolescent Psychiatry Section for Neuropsychology

    RWTH Aachen University · Universitätsklinikum Aachen

    Affiliation as printed

    Section for Neuropsychology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany

13. Karlijn L. Kooij

    University Medical Center Utrecht

    Affiliation as printed

    Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands

14. Stefanie Trinh Aachen Institute of Neuroanatomy

    RWTH Aachen University · Universitätsklinikum Aachen

    Affiliation as printed

    Institute of Neuroanatomy, University Hospital RWTH Aachen, Aachen, Germany

15. Benny van der Vijgh

    Altrecht GGZ

    Affiliation as printed

    Altrecht Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, The Netherlands

16. Annemarie Elburg

    Utrecht University · Altrecht GGZ

    Affiliation as printed

    Altrecht Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, The Netherlands

    Department of Clinical Psychology, Utrecht University, Utrecht, Netherlands

17. Michael D. Zeiler

    Medical University of Vienna

    Affiliation as printed

    Eating Disorders Unit at the Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria

18. John F. Baines

    Christian-Albrechts-Universität zu Kiel · Max Planck Institute for Evolutionary Biology

    Affiliation as printed

    Institute for Experimental Medicine, Kiel University, Kiel, Germany

    Max Planck Institute for Evolutionary Biology, Plön, Germany

19. Jochen Seitz Aachen Department of Child and Adolescent Psychiatry

    RWTH Aachen University · Universitätsklinikum Aachen

    Affiliation as printed

    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany

20. Beate Herpertz‐Dahlmann Aachen Department of Child and Adolescent Psychiatry

    RWTH Aachen University · Universitätsklinikum Aachen

    Affiliation as printed

    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital RWTH Aachen, Aachen, Germany