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

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.

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.

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.