The Stress-obesity Axis: a Metabolomics Approach Towards Personalized Nutrition in Adolescents (FAME)

The Stress-obesity Axis: a Metabolomics Approach Towards Personalized Nutrition in Adolescents (FAME)

The ultimate aim of this project is to establish a validated strategy that allows for personalized intervention in adolescents (11 to 17 years) whom are assigned a state of overweight or obesity.

The investigators will assess the following hypotheses:

• Weight condition is reflected by the fecal metabolome (WP1)
• Emotional stress is implicated in weight condition (WP1)
• Functionality of the gut microbiome is related to the diet-stress-obesity axis (WP2)
• Dietary pattern impacts the fecal metabolome and gut microbiome (WP2)
• Personalized dietary intervention outperforms generalized dietary approaches (WP3)

Participants will:

• Produce a saliva, stool and hair sample
• Fill in questionnaires regarding mental health, medical health and demographic information
• Fill in a food frequency questionnaire and a 24-hrecalls
• Be measured (height, weight, fat% and waist circumference)

The samples will be analyzed using a technique called metabolomics to identify biomarker candidates with diagnostic and/or prognostic potential. Additionally, microbiome analysis will be performed to map the microbiome of all groups.

Study Overview

• Status: Recruiting
• Conditions: Pediatric Obesity
• Intervention / Treatment: Other: Collection of anthropometric data, biological samples (stool, saliva and hair), questionnaires (demographic data, psychological data, medical data)

Detailed Description

In WP1, the investigators will assess the metabolic mechanisms underlying the obesity pathology in adolescents, whereby the involvement of emotional stress, will be of particular interest. To this end, a dual strategy fecal metabolomics will be performed: targeted profiling and untargeted fingerprinting. A major objective in this respect is to metabolically segregate between the overweight/obesity and normal weight condition as well as to reveal metabolic singularities that specifically relate to emotional stress. Fecal material, saliva and a hair sample will be collected from adolescents (11 to 17 years). Assignment of a participant's stress state will be performed post-hoc and based on hair cortisol concentrations and scores from the psychological questionnaires. The samples will be collected at home and have to be frozen immediately after sample collection. The samples will be analyzed using a technique called metabolomics, using UHPLC-HRMS (Ultra-High Performance Liquid Chromatography coupled to High-Resolution Mass Spectrometry).

In WP2 the investigators will assess the microbiome and diet as drivers for obesity. Fecal samples will be subjected to DNA extraction and whole-metagenome shotgun sequencing will be performed using the Illumina HiSeq 2500 system (151 bp paired-end reads; Novogene). In order to collect data about both long- and short-term dietary intakes, participants will be provided with a FFQ and a 24-h recall.

Eventually, discovery of metabolite marker signatures and elucidation of mechanistic pathways will offer opportunities to stratify obese adolescents according to emotional stress status, microbial composition and dietary preferences.

In WP3, the new data from WP1/2 will be translated in personalized dietary recommendations. The investigators will assess the potential of dietary interventions focused on nutrient quality (not energy-reduced) to affect the stress-obesity axis directly or by gut microbial modulation. After ethical approval, the dietary intervention study will include up to 20 individuals that were allocated to the overweight/obesity group. In our 3-month personalized intervention, separate menus for each participant will be prepared by our dietician. Based on WP1/2 and literature evidence, appropriate changes in nutrients will be aimed for. At different points in time, fecal samples will be collected, aliquoted and biobanked at -80°C. Fecal samples will be used for polar metabolomics and lipidomics analyses and microbiome metasequencing. At the start and after the 3-months intervention, fasting blood samples will be taken for clinical biomarkers (glucose, insulin, cholesterol, cytokines, ...). In addition, indirect calorimetry will determine resting energy expenditure. Anthropometric measures include BMI, waist and fat%. Questionnaires cover emotional eating (DEBQ), satiety, physical activity, sleep and quality-of-life (KINDL). Study volunteers will be asked to fill out an FFQ and 3-day 24-h recall to assess dietary habits prior to the trial.

• Study Type: Observational
• Enrollment (Estimated): 750

Contacts and Locations

• Study Contact: Name: Lynn Vanhaecke, Prof; Phone Number: 0032 9 264 74 57; Email: Lynn.Vanhaecke@ugent.be
• Study Contact Backup: Name: Emile Callemeyn, Dr; Phone Number: +32473271636; Email: emile.callemeyn@ugent.be

Study Locations

• Belgium
  • Antwerpen, Belgium, 2000
    • Recruiting
    • UZ Antwerpen
    • Contact: Karolien Van de Maele, Prof; Phone Number: +32 3 821 32 51; Email: karolien.vandemaele@uza.be
  • Antwerpen, Belgium, 2000
    • Recruiting
    • ZNA Middelheim
    • Contact: Daniel Klink, Dr; Email: daniel.klink@zna.be
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • AZ Jan Palfijn Gent, Oost-Vlaanderen, Belgium, 9000
      • Contact: Nele Baeck, Dr; Email: Nele.Baeck@janpalfijngent.be
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • Ghent university Hospital
      • Contact: Stefaan de Henauw, Prof; Phone Number: +32 9 332 36 79; Email: Stefaan.deHenauw@UGent.be
  • Waals Brabant
    • Ottignies-Louvain-la-Neuve, Waals Brabant, Belgium, 1340
      • Recruiting
      • Clairs Vallons
      • Contact: Laure Joachim, Dr; Email: laurejoachim@clairsvallons.be
  • West-Vlaanderen
    • De Haan, West-Vlaanderen, Belgium, 8420
      • Recruiting
      • Zeepreventorium
      • Contact: Ann Tanghe; Email: Ann.tanghe@zeepreventorium.be
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Recruiting
      • AZ Delta
      • Contact: Els Ide, dr; Email: els.ide@azdelta.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Volunteers with normall weight and overweight/obesity are being recruited from several hospitals (UZ Ghent, AZ Jan Palfijn, UZ Antwerpen, ZNA Middelheim, AZ Delta Roeselare, UZ Brussel, UZ Leuven, Onze-Lieve-Vrouw Ziekenhuis Aalst, AZ Sint-Lucas Brugge, AZ Sint-Elizabeth Zottegem, Zeepreventorium, Clairs Vallons) and schools (Don-Bosco Sint-Denijs-Westrem, Leiepoort Deinze, Broederschool Sint-Niklaas, SFI Melle) in Belgium

Description

Inclusion Criteria:

• Age 11-17 years

Exclusion Criteria:

• Obesity/overweight
• Type 1 diabetes
• Medical conditions including pancreatic failure
• Developmental and hormonal disorders. E.g. thyroid problems, adrenal problems, Kallmann's syndrome, Klinefelter's syndrome, Prader-Willi syndrome (PWS), Congenital hypogonadotropic hypogonadism (CHH), ...
• Pregnancy
• In treatment with systemic concentrations of corticosteroids (cortisone). Eg cortisone/betamethasone/Dexamethasone/Fludrocortisone/Hydrocortisone in pill form or administration by injections.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Overweight/obese; BMI-Z > 25	Other: Collection of anthropometric data, biological samples (stool, saliva and hair), questionnaires (demographic data, psychological data, medical data); Saliva and feces are collected at the families home. A questionnaire is filled in by the participant (psychological) and parents (demographical and medical info). Upon consultation we are collecting anthropometric data (date of birth, length, weight, abdominal circumference, Tanner pubertal stage, etc.)
Normal weight; BMI-Z < 25	Other: Collection of anthropometric data, biological samples (stool, saliva and hair), questionnaires (demographic data, psychological data, medical data); Saliva and feces are collected at the families home. A questionnaire is filled in by the participant (psychological) and parents (demographical and medical info). Upon consultation we are collecting anthropometric data (date of birth, length, weight, abdominal circumference, Tanner pubertal stage, etc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomics	Saliva and fecal samples will be analyzed using a technique called metabolomics, which analyses all small molecules (metabolites) present in a biological fluid. These metabolites will be used to find biomarkers that are related to the disease and could have diagnostic or prognostic potential. Additionally, these metabolites could give more insights into the development and maintenance of the disease.	Samples will be analyzed in the 4th quarter of 2024.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome analysis	The microbiomes of all groups will be analyzed because it has been described in literature that the microbiome can differ between healthy and obese individuals	Microbiome analyses will be performed at the start of 2025
Stress levels	Assignment of a participant's stress state will be performed based on hair cortisol concentrations, and scores from the Perceived Stress Scale (PSS), the Children's Depression Inventory 2 (CDI-2) and the Rosenberg Self-Esteem Scale (RSES) questionnaires. A summary chronic stress variable will be calculated by adding up the four z-score-transformed variables to give them equal weight	Hair cortisol analyses will be conducted in the first quarter of 2025. Data processing of the questionnaires is an ongoing process, to be completed by the last quarter of 2024
Food frequency questionnaire	To collect data about dietary intakes, participants are provided with an FFQ. Participants are required to indicate the frequency of consumption for each food of interest, ranging from (almost) never, to a few times a week, (almost) daily, to multiple times a day. All responses are encoded into numerical values, representing the frequency of consumption for specific foods.	FFQ data are being analyzed continuously and will be finished when the sample collection is finished (estimated by the end of 2024)

Collaborators and Investigators

• Sponsor: University Ghent
• Investigators: Principal Investigator: Stefaan de Henauw, Prof, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: April 19, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Mass spectrometry; Metabolomic
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity
• Other Study ID Numbers: BC-10583

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No