Microbiome Shifts in Adolescent Anorexia Nervosa

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effect of starvation and recovery in adolescent anorexia nervosa patients in regard to microbiome activity and composition and to elucidate potential connections between weight gain, depression and other comorbidities, further to capture hormone levels and inflammation parameters in a longitudinal design.

Detailed Description
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Anorexia Nervosa (AN) has the highest mortality of all psychiatric disorders. Large part of all patients the disorder becomes chronical. Until now, no (bio-) markers which allow a prognosis of outcome are known. Recently the function of the intestinal microbiome and its effects on food uptake, immunological processes and barrier malfunctions in the intestine is discussed. Especially the concept of the leaky gut, an adsorption malfunction of the intestinal wall under starvation for antigens may help to explain the low inflammatory response which is commonly found in Anorexia Nervosa subjects and a connection to higher rate of autoimmune diseases by Anorexia Nervosa. Furthermore the presence and quantity of specific bacteria in the intestine seems to be dependent on patient's sex which would contribute to the gender gap of prevalence for Anorexia Nervosa. Stress induced changes of the HPA-axis which are well documented in Anorexia Nervosa patients and often persist even after weight rehabilitation, play an important part for intestinal wall permeability disorders. In the most often used animal model for AN, the Activity-Based Anorexia (ABA) model which combines nutrition restriction and weight loss with hyper activity, a malfunction in intestinal wall permeability was found. Malnutrition and long lasting dieting have a fast and reproducible impact on the intestinal microbiome. Especially animal derived food seems to support proliferation of pro-inflammatory bacteria. A substantial intestinal dysbiosis (reduced alpha-diversity) was found in AN patients which only partly recovered after weight rehabilitation. Reduction in diversity and composition of the microbiome was significantly associated with severity of depressive symptoms in patient, where severity is an indicator for higher level eating pathologies and poorer prognosis. Aim of this longitudinal study is therefore to investigate to interconnections between fecal microbiome and progression of AN, including associations with stress, inflammatory markers and metabolic markers in blood sera as well as clinical parameters such as severity of depression and eating pathologies.

Official Title
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Microbiome Shifts in Adolescent Anorexia Nervosa

Conditions
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Anorexia Nervosa

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients and volunteers between age 12 and 18 at inclusion. Written informed consent by Patient/volunteer and caregiver. Volunteers with BMI between 10 and 90 percentile of their age group. Volunteers without prior eating or mental disorder. Exclusion Criteria: Psychotic disorder(s) Personality disorder(s) Alcohol and substance abuse Prone to self-harming behaviour Primary caregiver insufficient German language skills Patient/Volunteers IQ lower 85 Antibiotic treatment within 4 weeks prior to inclusion

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>100 female patients between the age of 12 and 18 years suffering from anorexia nervosa. | |
| Age matched Controls<br>100 females volunteers between the age of 12 and 18 years old without eating disorder. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation BMI and Microbiome Variability | Correlation between Body Mass Index and Microbiome Variability. | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacteria | Qualitative description of bacteria species | 12 month | 
| Bacteria activity | Quantitative description of Bacterial activity | 12 month | 
| Inflammatory parameters |  | 12 month | 
| Depression | Depression assessment Beck's Depression Inventory II | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anorexia, Depression, Microbiome