Getting into the guts of eating disorders in children and adolescents, with a perspective from psychoneuroimmunology (the PSYNIGED study): an observational, longitudinal study protocol

Abstract

Abstract Background Eating disorders (ED) are severe and complex psychiatric conditions characterized by the presence of abnormal eating patterns. An integrative biopsychosocial model has been developed to describe vulnerability to developing an ED, as well as its maintenance and treatment resistance. Potential predisposing factors for anorexia nervosa (AN) include neurobiological and genetic factors, psychological traits and early life experiences. More specifically, dysregulation of brain neurotransmitters and the reward systems, appetite-regulating neuropeptides, the hypothalamic–pituitary–adrenal (HPA) axis and the bidirectional communication between the gut microbiome and the brain have all been pointed out . However, studies relevant to characterizing the gut microbiota features in AN patients are still scarce and more research is needed to discern the mechanisms operating in specific stages of the disease and in specific diagnostic subtypes. Thus, the objective of this project is to investigate differences in gut microbiota composition and microbial-related metabolite levels between children and adolescents experiencing their first episode of ED and matched healthy controls. Additionally, we will study the associations between psychological variables, dietary patterns, microbiota composition, and neuroendocrine and inflammatory variables to generate hypotheses about the most important factors in the pathophysiology of ED. Methods A cross-sectional, controlled study will be conducted with children and adolescents who have been newly diagnosed with an ED and have had symptoms for less than one year. Healthy preadolescents and adolescents will serve as the control group. The study will include an assessment of clinical status, medical history, early life experiences, psychometric tests, dietary patterns, and gut microbiota composition and function (shotgun metagenomics). Additionally, appetite-regulating peptides, neurotransmitters, inflammatory cytokines, and SCFAs will be analyzed. For patients willing to undergo a second assessment, clinical variables, microbiota, and blood biomarkers will be analyzed after one year of treatment. Discussion Understanding the regulatory mechanisms of physiological functions affected by ED, such as appetite control, reward systems, and energy homeostasis, as well as the role of gut microbiota in these systems, could help advance the design of personalized treatments. Trial registration ClinicalTrials.gov ID: NCT07066033. Released on July 3, 2025.