Longitudinal investigation of the microbiome-gut-brain axis in adolescent anorexia nervosa (MiGBAN 2.0)

Anorexia nervosa (AN) is a severe and multifaceted psychiatric disorder, characterised by distorted body image and profound neurobiological alterations. It is associated with substantial morbidity and has one of the highest mortality rates among mental illnesses. In recent years, the microbiome-gut-brain axis has been proposed as a potentially important pathway in AN. Both cross-sectional and longitudinal studies suggest that individuals with AN show alterations in gut microbiome composition, some of which may normalise with weight restoration. However, it remains unclear how strongly these microbial patterns relate to clinical outcomes or underlying neurobiological changes. Particularly, longitudinal evidence connecting microbiome profiles with brain structure and illness trajectory is scarce.

The MiGBAN 2.0 study is designed to address these gaps by investigating how the gut microbiome changes over time and how these changes relate to clinical and neurobiological outcomes in adolescents with AN. Its primary aim is to examine whether baseline microbiome composition can predict changes in body mass index (BMI) across a 12-month period. In addition, the study will explore how microbiome dynamics relate to depressive symptoms, eating disorder psychopathology, inflammatory markers, and alterations in brain structure and function.

This ongoing longitudinal study will recruit 100 adolescents (aged 12-18 years) with typical or atypical AN who are undergoing inpatient treatment, together with 50 age- and sex-matched healthy controls. Patients will be assessed at admission, discharge, and again at 12-month follow-up, whereas controls will complete assessments at baseline and follow-up only. Data collection is multimodal and includes stool samples for microbiome profiling, blood samples assessing hormonal and inflammatory markers, validated psychometric measures of depressive and eating disorder symptoms, neuropsychological testing, and structural and functional magnetic resonance imaging.

The primary outcome is the change in percentage median BMI over 12 months, with baseline gut microbiome composition serving as the main predictor. Secondary measures include changes in body weight and nutritional intake, alongside shifts in eating disorder psychopathology and microbial diversity. Additional variables capture inflammatory markers and microbial activity. A further key outcome concerns the severity of depressive symptoms. Longitudinal associations will be examined using linear mixed-effects models, with adjustment for relevant covariates such as age, sex, illness duration, and pre-admission weight loss. Further analyses will investigate how microbiome diversity relates to intestinal permeability (e.g. zonulin), inflammatory processes, and clinical outcomes.

As data collection is ongoing, results are not yet available. It is hypothesised that baseline microbiome composition will partially predict clinical trajectory and BMI at follow-up, and that microbiome changes will be associated with improvements in psychopathology and neurobiological measures.

By integrating longitudinal clinical data with biological and neuroimaging measures, this study seeks to advance understanding of the microbiome-gut-brain axis in AN. A more refined characterisation of these mechanisms may help identify prognostic microbial markers and inform the development of targeted interventions, ultimately supporting improved stratification and treatment for adolescents with AN.

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