Effect of POSTbiotics Supplementation on Microbiome in OBese Children: the POST-OB Study (POST-OB)

This study evaluates the possible effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, on gut microbiota composition and metabolite production. It also wants to determine whether postbiotics supplementation, combined with interventions to improve diet and lifestyle, reduces adverse metabolic consequences together with their co-morbidities.

All participants will follow a behaviour (promotion of physical activity) and dietary treatment according to Italian dietary guidelines for childhood obesity.

Postbiotics and vitamin D3 will be given orally for four months; patients will be evaluated four months after supplementation and diet-lifestyle intervention and four months after the end of supplementation and after the alone diet-lifestyle intervention with blood testing and echosonography of the liver.

Study Overview

• Status: Unknown
• Conditions: Childhood Obesity
• Intervention / Treatment: Drug: Vitamin D3; Drug: Immunofos; Other: Promotion of physical activity; Other: Healthy food habits promotion

Detailed Description

25-30 Caucasian obese children will be enrolled at the Pediatric Department of San Paolo Hospital - University of Milan.

Stool samples from all enrolled patients at the different time points (t0, before supplementation and diet-lifestyle intervention, t1, four months after supplementation and diet-lifestyle intervention and t2 four months after the end of supplementation and after the alone diet-lifestyle intervention) will be collected and stored at -80°C until the following investigation:

1. study of the microbiota biodiversity by high-throughput sequencing techniques (16S rRNA gene sequencing) in order to establish whether postbiotics could modulate the microbial composition in obese children;
2. analysis of short chain fatty acids concentration by gas-chromatography (GC-FID) in order to monitor the effect of postbiotics intake modulating microbial metabolite production.

The following tasks will be also performed at t0, t1 and t2:

• Clinical examination including: physical examination, Tanner score evaluation; Bristol Stool Chart
• Blood pressure will be checked in all children by using oscillometric devices validated in the pediatric age group.
• Anthropometry including body circumferences and skinfolds, calculation of BMI z scores and body composition. Body composition will be assessed using an air displacement plethysmography system (BOD POD COSMED-USA).

• Dietary assessment:

  1. Food intakes will be recorded by prospective 3-d weighed food records obtained with food scales. Parents will be advised on how to record all food and beverages consumed during 2 weekdays and 1 weekend day. Quantification and analysis of the energy intake and nutrient composition will be performed with an ad hoc PC software (MètaDieta®, Me.Te.Da S.r.l., San Benedetto del Tronto, Italy).

  2. Mediterranean Diet Quality Index (KIDMED) questionnaire for Mediterranean Diet assessment. The KIDMED index ranges from 0 to 12, and is based on a 16-question test that can be self-administered. The sums of the values from the administered test will be classified into three levels:

     1. 8 or more: optimal Mediterranean diet;
     2. 4-7: improvement needed to adjust intake to Mediterranean patterns.
     3. 3 or less: very low diet quality.

• Hematological and biochemical status including:

  1. Complete cell blood count;

  2. Metabolic and nutritional parameters according to local routines for childhood obesity (fasting glucose, fasting insulin, LDL, HDL, total cholesterol, triglycerides, Apolipoprotein A and Apolipoprotein B levels, transaminases and amma-glutamyl transferase). Oral Glucose Tolerance Test (OGTT) will be performed. The insulin sensitivity and insulin resistance was assessed by calculating HOMA index (Homeostasis Model Assessment) and QUICKI (Quantitative Insulin-Sensitivity Check Index), using the following formulas:

     • HOMA: fasting plasma insulin in mU/l x FPG in mmol/l/22.5
     • QUICKI: 1/(log10 fasting plasma insulin in mU/l + log10 glucose in mg/dl)
  3. Inflammatory index (VES, high-sensitive CRP, including fecal calprotectin)
• Liver ultrasonography will be performed by a single evaluator.

All participants will follow a behavior (promotion of physical activity) and dietary treatment according to Italian dietary guidelines for childhood obesity.

Postbiotics will be given at the dose of 80 mg/day (2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN; fermented fructooligosaccharides from Lactobacillus paracasei strain CNCM I-5220). 2 mk of product will give 1600 UI/die of VIT D3.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20142
    • Recruiting
    • Ospedale San Paolo
    • Contact: Elvira Verduci, MD PhD Assistant Professor; Phone Number: +39 0281844508; Email: elvira.verduci@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 6 <Age <14 years
• Severe obesity (>3 DS) according to WHO classification.
• Gestational age: 37-42 weeks.
• Birth-weight: > 2500 g e < 4000 g
• Caucasian

Exclusion Criteria:

• secondary obesity
• supplementation with pre/probiotics (in the previous 3 months);
• antibiotic treatment (in the previous 3 months);
• chronic or acute intestinal diseases (in the previous 3 months).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Postbiotic &vitamin D3, lifestyle intervention.; Postbiotics will be given at the dose of 80 mg/day (2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN; immunofos from Lactobacillus paracasei CNCM I-5220). 2 mL of product will give 1600 UI/die of VIT D3. Healthy living habits will be encouraged at t0, t1 and t2 visit.

Drug: Vitamin D3; 2 ml per day SMART D3 MATRIX Smartfarma S.r.l. Via San Vittore 40 - 20123 MILAN: 2 mL of product will give 1600 UI/die of VIT D3.; Drug: Immunofos; Postbiotics will be given at the dose of 80 mg/day. immunofos from Lactobacillus paracasei CNCM I-5220).; Other: Promotion of physical activity; Promotion of physical activity will be encouraged at t0, t1, t2; Other: Healthy food habits promotion; Promotion of healthy food habits will be encouraged at t0, t1, t2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiota composition	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in short chain fatty acids production by gut microbiota	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in HDL-cholesterol levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in LDL-cholesterol levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in triglycerides levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in systemic arterial blood pressure	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in body mass index	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in Bristol stool chart	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in puberal stage	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in fasting glucose levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in fasting insulin levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in oral glucose tolerance test results	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in Apoprotein A1 levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in Apoprotein B levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in alanine aminotransferase (ALT) levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in aspartate aminotransferase (AST) levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in Gamma-glutamyl transferase (GGT) levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in complete cell blood count	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in total cholesterol levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in Homeostasis Model Assessment (HOMA) index	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in Quantitative Insulin-Sensitivity Check Index (QUICKI)	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in erythrocyte sedimentation rate (ESR)	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in C-reactive protein (CRP) levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in fecal calprotectin levels	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Echosonographic changes in liver morphology (degree of steatosis)	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in body mass composition assessed with air displacement plethysmography system	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in body circumference (waist, left arm)	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months
Changes in body skinfold thickness (waist, posterior skinfold and anterior skinfold of left arm)	Effect of postbiotics supplementation, combined with interventions aimed at improving diet and lifestyle, will be evaluated. Difference in gut microbiota composition will be evaluated before starting supplementation (t0), at the end of supplementation (t1: +4 months) e after 4 months of dietary dietary-lifestyle intervention without supplementation (t2: +8 months).	t0: 0 t1: +4 months t2: +8 months

Collaborators and Investigators

• Sponsor: University of Milan

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Anticipated): January 7, 2021
• Study Completion (Anticipated): January 7, 2021

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 28, 2020
• Last Update Submitted That Met QC Criteria: July 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Nutrition; Gut microbiota; Childhood obesity; Postbiotics
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2015/ST/135-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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