PROBESITY-2: Synbiotics in Pediatric Obesity (PROBESITY-2)

Effects Of Synbiotic Supplementation On Anthropometric Measurements, Glucose Metabolism, Lipid Parameters And Intestinal Microbiota Composition In Children With Exogenous Obesity: (Probesity-2 Study)

The global obesity epidemic presents an unprecedented challenge to the public health worldwide. The factors associated with obesity are complex, and include health behaviours, such as eating habits and daily physical activity, and broader social, environmental and biological determinants that influence these health behaviours. The intestinal microbiota has several beneficial functions related to host health and accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. Recent studies have suggested some beneficial effects of probiotics and/or prebiotics on obesity and metabolic syndrome in adults; such experience is limited in children and adolescents. There are limited information about the synbiotics in children and adolescent with obesity.The mechanism of action of probotics on obesity are scarce and microbiota restoration/reshaping might be the one. The objective of this study tested the effects of a multispecies synbiotic on anthropometric measurement, glucose metabolism, lipid parameters and intestinal microbiota in children with exogenous obesity.

Study Overview

• Status: Completed
• Conditions: Obesity, Childhood; Obesity, Adolescent
• Intervention / Treatment: Dietary supplement: Synbiotic

Detailed Description

The global obesity epidemic presents an unprecedented challenge to the public health worldwide. The factors associated with obesity are complex, and include health behaviours, such as eating habits and daily physical activity, and broader social, environmental and biological determinants that influence these health behaviours. The intestinal microbiota has several beneficial functions related to host health and accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. Recent studies have suggested some beneficial effects of probiotics and/or prebiotics on obesity and metabolic syndrome in adults; such experience is limited in children and adolescents. There are limited information about the synbiotics in children and adolescent with obesity.The mechanism of action of probotics on obesity are scarce and microbiota restoration/reshaping might be the one. The objective of this study tested the effects of a multispecies synbiotic on anthropometric measurement, glucose metabolism, lipid parameters and intestinal microbiota in children with exogenous obesity.

This is a randomized, double-blind, placebo-controlled clinical study with 61 children, aged between 8 to 17 years-old, with exogenous obesity which received a daily dose of a multispecies symbiotic formulation or a placebo for 12 weeks. At entry, the anthropometric measures included weight, height, waist and hip circumference were recorded. Waist circumference to height ratio, waist circumference to hip circumference ratio and body mass index (BMI) was calculated. Venous blood samples were drawn after a minimum 8 hours fasting for measures including serum glucose, insulin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, C-reactive protein (CRP), erythrocyte sedimentation rate; at admission and 12 weeks later. Both groups were treated with a standard diet and increased physical activity. Patients were randomly allocated into two groups in a ratio of 1:1. Randomization with permutated blocks was done using the online software tool. First group received a daily synbiotic supplementation which consisted of a daily probiotic mixture including Lactobacillus acidophilus), Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium (total 2.5 x109CFU/sachet), fructooligosaccharydes (FOS) 625 mg, lactulose 400 mg, vitamin A (6 mg), B1 (1.8 mg), B2 (1.6 mg), B6 (2.4 mg), E (30 mg), C (75 mg) for 12 weeks. Second group received placebo for 12 weeks. Each visit (Day 0 and 12 weeks later), stool samples were also collected. The V3 and V4 regions of the 16S rRNA gene were amplified following the 16S Metagenomic Sequencing Library Preparation. The primary end point of this study was to evaluate the effect of the multispecies synbiotic would on weight loss (reduction as percentage for weight and body mass index). Secondary endpoints were the evolution of the other anthropometeic measurements, glucose and lipid metabolism and intestinal microbiota composition.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Odunpazarı
    • Eskisehir, Odunpazarı, Turkey, 26040
      • Eskisehir Osmangazi University Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children and adolescents
• Aged between 8 to 17 years old with exogenous obesity

Exclusion Criteria:

• Children and adolescents with endogenous obesity
• Children with adolescents with a history of gastrointestinal surgery
• Children with adolescents with chronic intestinal disorders including inflammatory bowel disease
• Children receiving probiotics and /or antibiotics 8 weeks prior this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synbiotic; Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium (total 2.5 x10 9CFU/sachet), fructooligosaccharydes (FOS) 625 mg, oral sachet daily, for 12 weeks	Dietary supplement: Synbiotic; Oral sachet, for 12 weeks
Placebo Comparator: Placebo; Oral sachet daily for 12 weeks	Dietary supplement: Synbiotic; Oral sachet, for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change as percentage for weight and body mass index.	% reduction comparing to baseline	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change as percentage of anthropometric measurement	Waist circumference, hip circumference, waist/hip ratio, waist/height ratio	12 weeks
Change of glucose metabolism	Reduction as percentage of HOMA-IR	12 weeks
Change of lipid metabolism	Serum total cholesterol, LDL-C, HDL-C, serum triglyceride	12 weeks
Change of Intestinal microbiota composition	Change of predominant bacterial genera	12 weeks

Collaborators and Investigators

• Sponsor: Eskisehir Osmangazi University
• Investigators: Principal Investigator: Ener C Dinleyici, MD, Eskisehir Osmangazi University Faculty of Medicine

Publications and helpful links

General Publications

• Kilic Yildirim G, Dinleyici M, Vandenplas Y, Dinleyici EC. Effects of Multispecies Synbiotic Supplementation on Anthropometric Measurements, Glucose and Lipid Parameters in Children With Exogenous Obesity: A Randomized, Double Blind, Placebo-Controlled Clinical Trial (Probesity-2 Trial). Front Nutr. 2022 Jul 1;9:898037. doi: 10.3389/fnut.2022.898037. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Obesity; Microbiome; Microbiota; Synbiotic
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity
• Other Study ID Numbers: PROB2018

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