Impact of Dietary Fiber as Prebiotics on Intestinal Microbiota in Obese Thai Children

Study Overview
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Brief Summary
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This study evaluates the changes of gut microbiota composition and diversity, body weight, body fat, SCFAs, plasma amino acids, satiety hormones (Peptide-YY(PYY) and glucagon-like peptide(GLP-1)), Inflammatory cytokines (Interleukin-1β(IL-1β), Tumor necrosis factor-α (TNF-α) and Interleukin-6(IL-6)) after 6-month studied period in obese Thai children.165 participants Children, age 7 to 15 years with Body mass index (BMI) ≥ median + 2 standard deviation(SD) will be randomized into one of the three arms of 55 participants per group.Group A (intervention group) will receive inulin 10 g.Group B will receive placebo of isocaloric maltodextrin. Group C will receive dietary fiber advice aimed to match the recommended fiber intake for age.

Detailed Description
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The prevalence of childhood obesity is increasing worldwide. The prevalence of overweight and obesity in children and adolescents has risen dramatically from 4% to 18% in 40 years. Cause of obesity is gene-environment interactions. Recent evidence suggests that the gut microbiota is involved in energy regulation as well as inflammation Definition of obesity for children and teens is defined as a BMI at or above median +2 standard deviation(SD) of the same age and sex from World Health Organization (WHO) reference Management of childhood obesity are therapeutic lifestyle change by changing dietary habits and the physical activity level. Consumption of prebiotics, which are non-digestible polysaccharides that utilized by gut microorganisms then microbial shifts in response to prebiotic intake change in Bifidobacterium and lead to decreased body weight and adiposity. The microbial metabolite short-chain fatty acids (SCFAs) are likely to have impacts on various aspects of host physiology and then may decrease in body weight and adiposity. The mechanism of inflammation in obesity, Lipopolysaccharides (LPS) which derived from the outer cell membrane of Gram-negative bacteria are the trigger factor of inflammation.LPS cross the gastrointestinal mucosa, then they reach the systemic circulation and trigger innate immune response activate the maturation of IL-1β. Circulating LPS levels were associated with elevated TNF-α and IL-6 concentrations in adipocytes. Inulin-type fructans are non-digestible, fully soluble, and fermentable food ingredients with known prebiotic properties, which are found naturally in chicory root and Jerusalem artichoke, a plant grown in Thailand, that are fermented in the colon to produce SCFA. Bifidobacteria are preferentially stimulated to grow, by increasing the number of health-promoting bacteria and reducing the number of potentially harmful species. There was only one study about the effect of prebiotics on composition of the intestinal microbiota in children with overweight or obesity. The study performed a randomized controlled trial to study children, 7-12 years old, with overweight or obesity. Participants were randomly assigned to groups given either oligofructose-enriched inulin (OI; 8 g/day; n = 22) or maltodextrin placebo (isocaloric dose, controls; n = 20) once daily for 16 weeks. Fecal samples were collected at baseline and 16 weeks and the composition of the microbiota was analyzed by 16S ribosomal ribonucleic acid (rRNA) sequencing and qPCR. The primary outcome was change in percent body fat from baseline to 16 weeks. After 16 weeks, quantitative polymerase chain reaction(qPCR) showed a significant increase in Bifidobacterium spp. in the OI group compared with controls. 16S rRNA sequencing revealed significant increases in species of the genus Bifidobacterium and decreases in Bacteroides vulgatus within the group who consumed OI.children who consumed OI had significant decreases in body weight z-score (decrease of 3.1%), percent body fat (decrease of 2.4%), percent trunk fat (decrease of 3.8%), interleukin 6 from baseline (decrease of 15%) compared with children given placebo.

Official Title
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Impact of Dietary Fiber as Prebiotics on Intestinal Microbiota in Obese Thai Children

Conditions
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Obesity

Intervention / Treatment
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* Dietary Supplement: Inulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children, age 7 to 15 years Body mass index (BMI) ≥ median + 2 Standard deviation (SD) Exclusion Criteria: Underlying disease of syndromic obesity and monogenic obesity Endocrine causes of obesity (e.g. hypothyroidism, growth hormone deficiency) Use of drugs that influence appetite or body weight (e.g. corticosteroids) Attending other concurrent weight reduction programs

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 165 participants Children, age 7 to 15 years with Body mass index (BMI) ≥ median + 2 Standard deviation(SD) will be randomized into one of the three arms of 55 participants per group.Group A (intervention group) will receive inulin 10 g.Group B will receive placebo of isocaloric maltodextrin. Group C will receive dietary fiber advice aimed to match the recommended fiber intake for age.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inulin<br>Group A (intervention group) will receive inulin 10 g. | Dietary Supplement: Inulin<br>* Group A (intervention group) will receive inulin 10 g.Group B will receive placebo of isocaloric maltodextrin. Group C will receive dietary fiber advice aimed to match the recommended fiber intake for age.This study evaluates the changes of gut microbiota composition and diversity, body weight, body fat, SCFAs, plasma amino acids, satiety hormones (PYY and GLP-1), Inflammatory cytokines (IL-1β, TNF-α and IL-6) after 6-month studied period<br>* Other names: Maltodextrin;|
| Placebo Comparator: Maltodextrin<br>Group B will receive placebo of isocaloric maltodextrin. | Dietary Supplement: Inulin<br>* Group A (intervention group) will receive inulin 10 g.Group B will receive placebo of isocaloric maltodextrin. Group C will receive dietary fiber advice aimed to match the recommended fiber intake for age.This study evaluates the changes of gut microbiota composition and diversity, body weight, body fat, SCFAs, plasma amino acids, satiety hormones (PYY and GLP-1), Inflammatory cytokines (IL-1β, TNF-α and IL-6) after 6-month studied period<br>* Other names: Maltodextrin;|
| Active Comparator: Dietary fiber<br>Group C will receive dietary fiber advice aimed to match the recommended fiber intake for age. | Dietary Supplement: Inulin<br>* Group A (intervention group) will receive inulin 10 g.Group B will receive placebo of isocaloric maltodextrin. Group C will receive dietary fiber advice aimed to match the recommended fiber intake for age.This study evaluates the changes of gut microbiota composition and diversity, body weight, body fat, SCFAs, plasma amino acids, satiety hormones (PYY and GLP-1), Inflammatory cytokines (IL-1β, TNF-α and IL-6) after 6-month studied period<br>* Other names: Maltodextrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota (16S rRNA sequencing) | Relative abundant of gut microbiota phyla (focus on Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria) | Change from baseline in gut microbiota at 3 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body mass index (BMI) | Weight in kilograms and height in meters will be combined to report BMI in kg/m^2 | Change from baseline in body mass index at 1,2,3,4,5 and 6 months | 
| Short chain fatty acids | Acetate, propionate and butyrate (By High Performance Liquid Chromatography) | Change from baseline in acetate, propionate and butyrate at 3 months | 
| Inflammatory cytokines (ELISA method)(IL-1β, TNF-α and IL-6) | Inflammatory cytokine (ELISA method)(IL-1β(pg/ml), TNF-α (pg/ml) and IL-6(pg/ml)) | Change from baseline in inflammatory cytokines (ELISA)(IL-1β, TNF-α and IL-6) at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prebiotics, Intestinal Microbiota