Clinical trial NCT03968003: Impact of Dietary Fiber as Prebiotics on Intestinal Microbiota in Obese Thai Children
Official title: Impact of Dietary Fiber as Prebiotics on Intestinal Microbiota in Obese Thai Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Prebiotics
Intestinal Microbiota
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
First posted: 2019-05-30
Enrollment: 165
Sex: ALL
Minimum age (years): 7
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: This study evaluates the changes of gut microbiota composition and diversity, gut-muscle axis, body weight, body fat, children eating behaviours, SCFAs, plasma amino acids, satiety hormones (Peptide-YY(PYY) and glucagon-like peptide 1(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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in gut microbiota (16S rRNA sequencing) at 3 and 6 months
timeFrame: From the enrollment to 3 months and the end of intervention at 6 months.
Secondary outcomes:
measure: Change from baseline in Body mass index (BMI) at 1,2,3,4,5 and 6 months
timeFrame: From the enrollment to monthly visit and the end of intervention at 6 months.
measure: Change from baseline in fat mass index (FMI) at 6 months
timeFrame: From the enrollment to 3 months and the end of intervention at 6 months.
measure: Change from baseline in fecal short chain fatty acids (SCFAs) at 3 and 6 months
timeFrame: From the enrollment to 3 months and the end of intervention at 6 months.
measure: Change from baseline in Inflammatory cytokines (ELISA method)(IL-1β, TNF-α and IL-6) at 6 months
timeFrame: From the enrollment to the end of intervention at 6 months.
measure: Change from baseline in Children Eating Behaviors at 3 and 6 months
timeFrame: From the enrollment to 3 months and the end of intervention at 6 months.
measure: Change from baseline in serum GLP-1 hormone at 6 months.
timeFrame: From enrollment to the end of intervention at 6 months
measure: Change from baseline in PYY hormone at 6 months
timeFrame: From enrollment to the end of intervention at 6 months.
measure: Change from baseline in myokine (interleukin-15) at 6 months
timeFrame: From enrollment to the end of intervention at 6 months.
measure: Change from baseline in creatinine/cystatin C ratio at 6 months
timeFrame: From enrollment to the end of intervention at 6 months.
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Chulalongkorn University
Study officials:
affiliation: Chulalongkorn University
name: Chonnikant Visuthranukul, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Visuthranukul C, Leelahavanichkul A, Tepaamorndech S, Chamni S, Mekangkul E, Chomtho S. Inulin supplementation exhibits increased muscle mass via gut-muscle axis in children with obesity: double evidence from clinical and in vitro studies. Sci Rep. 2024 May 16;14(1):11181. doi: 10.1038/s41598-024-61781-1.
citation: Visuthranukul C, Sriswasdi S, Tepaamorndech S, Chamni S, Leelahavanichkul A, Joyjinda Y, Aksornkitti V, Chomtho S. Enhancing gut microbiota and microbial function with inulin supplementation in children with obesity. Int J Obes (Lond). 2024 Dec;48(12):1696-1704. doi: 10.1038/s41366-024-01590-8. Epub 2024 Jul 20.
citation: Visuthranukul C, Sriswasdi S, Tepaamorndech S, Joyjinda Y, Saengpanit P, Kwanbunbumpen T, Panichsillaphakit E, Uaariyapanichkul J, Chomtho S. Association of Human Intestinal Microbiota with Lifestyle Activity, Adiposity, and Metabolic Profiles in Thai Children with Obesity. J Nutr Metab. 2022 May 20;2022:3029582. doi: 10.1155/2022/3029582. eCollection 2022.
citation: Visuthranukul C, Chamni S, Kwanbunbumpen T, Saengpanit P, Chongpison Y, Tepaamorndech S, Panichsillaphakit E, Uaariyapanichkul J, Nonpat N, Chomtho S. Effects of inulin supplementation on body composition and metabolic outcomes in children with obesity. Sci Rep. 2022 Jul 29;12(1):13014. doi: 10.1038/s41598-022-17220-0.
citation: Visuthranukul C, Kwanbunbumpen T, Chongpison Y, Chamni S, Panichsillaphakit E, Uaariyapanichkul J, Maholarnkij S, Chomtho S. The Impact of Dietary Fiber as a Prebiotic on Inflammation in Children with Obesity. Foods. 2022 Sep 15;11(18):2856. doi: 10.3390/foods11182856.
citation: Panichsillaphakit E, Chongpison Y, Saengpanit P, Kwanbunbumpen T, Uaariyapanichkul J, Chomtho S, Pancharoen C, Visuthranukul C. Children's Eating Behavior Questionnaire Correlated with Body Compositions of Thai Children and Adolescents with Obesity: A Pilot Study. J Nutr Metab. 2021 Jan 15;2021:6496134. doi: 10.1155/2021/6496134. eCollection 2021.
citation: Saengpanit P, Chomtho S, Sriswasdi S, Rodpan A, Joyjinda Y, Panichsillaphakit E, Uaariyapanichkul J, Tempark T, Bongsebandhu-phubhakdi C, Suteerojntrakool O, Visuthranukul C. Dietary fiber intake and its relationships with lipid profiles and gut microbiota in obese Thai children: a pilot study. J Med Assoc Thai . 2019;102:1282-8.