A Study of the Intestinal Microbiota in Children and Adolescents With Eating Disorders. A Perspective From Psychoneuroimmunology

NCT ID: NCT07066033

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 158 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-08-29
• Study Completion Date: 2027-08-31

Brief Summary

The goal of this observational study is to learn if behavioral and psychological factors are associated with the intestinal microbiota composition and function in children and adolescents with eating disorders (ED). The main questions it aims to answer are:

• Are there any differences between the microbiota composition and function in adolescent patients with eating disorders and healthy adolescents?
• Are the dietary pattern and other lifestyle habits associated with the intestinal microbiota composition in patients with a recent onset eating disorder?
• Is it possible to predict the treatment response at one year by looking at any of the psychological and biological factors measured in the patients at baseline?
• Are there any differences in the intestinal microbiota among patients with different subtypes of anorexia nervosa (restrictive, binge-purging, atypical) or with avoidance/restrictive food intake disorder (ARFID)? Researchers will compare the results with those obtained from a group of healthy children and adolescents matched by sex and age to find out if the associations observed differ between ED and control participants.

Participants with ED will fill in different lifestyle questionnaires and psychological tests; they will also undergo anthropometrical measurements and will provide fecal and blood samples at baseline and one year later. Healthy participants will provide the same lifestyle information, anthopometrical measurements and stool and blood samples. They will only undergo the baseline evaluation.

Detailed Description

BACKGROUND: Eating disorders (ED) are severe and complex psychiatric pathologies characterised by the presence of abnormal eating patterns. There is not an easy cure, the clinical courses are long and often present medical, psychiatric and family complications that influence their evolution and prognosis. Almost half of the patients continue with symptoms many years after their first episode. So far, the etiology of AN remains unclear but it certainly seems to encompass multiple intertwined genetic and environmental factors, that seem to affect appetite, behavioral pathways, psychological traits and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Socio-cultural and familiar factors may favor the onset of an ED. More specifically, there are hypotheses involving brain neurotransmitters and dysregulation of reward systems, via pathways in which the gut-brain axis may be involved. The gut microbiota synthesizes or regulates the production of short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, and various neurotransmitters and hormones that may affect the central nervous system.

AIM: the study investigates whether the composition and function of the intestinal microbiota in children and adolescents with eating disorders are different from those of healthy children and adolescents. Secondarily, the relationship between the dietary pattern prior to enrollment, the psychopathology symptoms and the intestinal microbiota will be assessed.

STUDY DESIGN: a cross-sectional controlled study will be performed where the microbiota of children and adolescents with ED (AN any subtype or ARFID) will be compared with that of healthy participants matched by sex and age.

SUBJECTS: All patients referred to the specialized ED unit of the Hospital Infantil Universitario Niño Jesús that fulfill inclusion and exclusion criteria and who are willing to participate will be included. Diagnosis will be performed by psychiatrists with DSM-5 criteria.

The following information will be gathered during the interview: i) developmental history, ii) medical and psychiatric history, iii) Behaviors around the ED, iv) psychopharmacological treatment, v) sleep quality and quantity.

Healthy children and adolescents matched by sex and age will be included used as control group, who will be enrolled at their education centers.

BIOMARKER ANALYSES:

1. anthropometry and body composition study (BMI Z-score, arm circumference and tricipital skinfold thickness, bioimpedance analysis)

2. blood biomarkers: hematology, routine biochemistry, insulin, cortisol, T3; Leptin, active Ghrelin, Total PYY, active GLP-1, adiponectin, plasma inflammatory cytokines, intestinal permeability mediators of inflammation and neurotransmitters.

3. fecal biomarkers: intestinal microbiota composition analysis using shot-gun metagenomic and deep sequencing and functional genetic mechanisms; neurotransmitters (HPLC), short-chain fatty acids.

PSYCHOMETRIC TESTS: aiming the assessment of i) ED specific psychopathology (EDI-II) ii) comorbidities (anxiety and depression), iii) personality, iv) stressful life events. The family will also fill in i) ED symptoms, ii) care giver experience, iii) parental functioning.

DIETARY STUDY: includes i) 24-hour recall, ii) food frequency questionnaire over the last 15 days and iii) questionnaire on dietary habits. Dietary patterns and diet quality indexes will be derived.

STOOL PROCESSING: Stool samples, at least the size of a walnut are stored at -80C until different aliquots are separated and weighed into processing tubes for the different techniques. For fecal microbiota composition analysis specimens are analyzed as follows: bacterial DNA extraction with chromatographic column and a prior optimization step, shot-gun Illumina DNA sequencing, generation of Operational Taxonomic Unit (OTU) tables at different taxonomic levels, functional gene annotation. The DNA purification is done at the Institute of Food Science, Technology and Nutrition, CSIC and the shot-gun sequencing and bioinformatic analysis at the Microbiological Unit of the Hospital Ramón y Cajal, Madrid, Spain.

SAMPLE SIZE: previous data on microbiota in the pediatric population with ED are lacking as well as those of healthy children from the reference population. The sample size calculation performed was based on an expected effect of moderate-large size according to published findings comparing AN patients and healthy women microbiota and SCFA. For the current study to prove a medium effect size (d=0.45) in the microbiota variables with a confidence level 95% and power 80%, the result was 79 subjects per group. The ex-post power of the differences observed will be calculated.

STATISTICAL METHODS: To identify significant and predictive factors among psychological, clinical and biological variables studied, multivariate predictive models will be run on the different outcomes: binary and multidimensional. The predictive models will be chosen according to the statistical restrictions of the data.

ONE YEAR FOLLOW UP ASSESSMENT: one year after entering the study, participating patients, only, will be evaluated with the same procedures as in the baseline study to check the differences in microbiota composition with time and study potentially prognostic factors.

ETHICS: The study is approved by the Research Ethics Committee at the Hospital Infantil Universitario Niño Jesús (reference number: 0068/23. 28 November 2023) and the Ethics Committee at the Spanish National Research Council (CSIC) (reference number: 245/2023. 22 January 2024). All sensitive information of personal or biological origin will be treated with confidentiality and according to the Spanish law. All biological specimens will be treated according to specified storage, reutilization and discarding procedures as consented by the participating subjects or their legal representatives.

PERSPECTIVES: The results and findings derived from this study will help understand whether the intestinal microbiota contributes to AN etiopathology and might provide evidence to support treatment strategies for personalized treatments and better disease prognosis.

Conditions

Eating Disorders in Adolescence; Eating Disorders in Children

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Eating disorder patients

Children and adolescents with a recent onset eating disorder initiating treatment in a Specialized Eating Disorder Unit

No interventions assigned to this group

Control group

Healthy children and adolescents matched by age and sex with the ED patients

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Age: 7-17.9 years
• Diagnosis of Anorexia Nervosa, both restrictive (ANR) and binge-purging (ANBP) subtypes, Other Specified Feeding and Eating Disorders (OSFED), Avoidant/Restrictive Food Intake Disorder (ARFID) according to DSM-V (APA, 2013).
• Males and females
• First episode or less than 1 year evolution since initial symptoms
• Written informed consent by parent/tutor and also by the adolescent if age is more than 12 y.

Exclusion Criteria

• Comorbidities: Current infectious disease at admission; Severe neurodevelopmental disorders with impaired language development; Moderate or severe intellectual disability; Endocrine disorders such as diabetes mellitus or thyroid disease; Celiac disease; Suicidal behaviors in the previous 3 months.
• Patients with previous unsuccessful treatments for more than one year.
• Use of the following medications before entering the study: laxatives, anabolic steroids, immunosuppressant drugs, Helicobacter pylori eradication treatment, thyroid hormones or antibiotic treatment in the previous two months

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Spanish National Research Council (ICTAN, CSIC)

UNKNOWN

Sponsor Role: collaborator

FUNDACION PARA LA INVESTIGACIÓN BIOMÉDICA HOSPITAL INFANTIL UNIVERSITARIO NIÑO JESUS

UNKNOWN

Sponsor Role: collaborator

Esther Nova

OTHER_GOV

Sponsor Role: lead

Responsible Party

Esther Nova

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Esther Nova, PhD

Role: STUDY_CHAIR

Spanish National Research Council (CSIC - ICTAN)

Mar Faya, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Infantil Universitario Niño Jesús

Locations

Hospital Infantil Universitario Niño Jesús

Madrid, Madrid, Spain

Site Status: RECRUITING

Institute of Food Science and Technology and Nutrition (ICTAN, CSIC)

Madrid, Madrid, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Esther Nova, PhD

Role: CONTACT

enova@ictan.csic.es

34 5492300 ext. 436322

Facility Contacts

Mar Faya, PhD, MD

Role: primary

mar.faya@salud.madrid.org

34 915744669 ext. 410747

Esther Nova, PhD

Role: primary

enova@ictan.csic.es

34 915492300 ext. 436322

Other Identifiers

PID2022-136588OB-C21

Identifier Type: -

Identifier Source: org_study_id