Prebiotic Reduces Body Fat and Alters Intestinal Microbiota in Children With Overweight or Obesity


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Prebiotic Reduces Body Fat and Alters Intestinal Microbiota in Children With Overweight or Obesity

Alissa C. Nicolucci, Megan P. Hume, Inés Martínez, Shyamchand Mayengbam, Jens Walter, Raylene A. Reimer'Correspondence information about the author Raylene A. ReimerEmail the author Raylene A. Reimer
Open AccessArticle has an altmetric score of 123
DOI: http://dx.doi.org/10.1053/j.gastro.2017.05.055
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Publication History
Published online: June 05, 2017
Accepted: May 30, 2017
Received in revised form: May 25, 2017
Received: April 6, 2017
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Abstract
Background & Aims
It might be possible to manipulate the intestinal microbiota with prebiotics or other agents to prevent or treat obesity. However, little is known about the ability of prebiotics to specifically modify gut microbiota in children with overweight/obesity
or reduce body weight. We performed a randomized controlled trial to study the effects of prebiotics on body composition, markers of inflammation, bile acids in fecal samples, and composition of the intestinal microbiota in children with overweight or
obesity.

Methods
We performed a single-center, double-blind, placebo-controlled, trial of 2 separate cohorts (March 2014 and August 2014) at the University of Calgary in Canada. Participants included children, 7 – 12 years old, with overweight or obesity (>85th
percentile of body mass index) but otherwise healthy. 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. Fat mass
and lean mass were measured using dual-energy-x-ray absorptiometry. Height, weight, and waist circumference were measured at baseline and every 4 weeks thereafter. Blood samples were collected at baseline and 16 weeks, and analyzed for lipids, cytokines,
lipopolysaccharide, and insulin. Fecal samples were collected at baseline and 16 weeks; bile acids were profiled using high-performance liquid chromatography and the composition of the microbiota was analyzed by 16S rRNA sequencing and quantitative PCR.
The primary outcome was change in percent body fat from baseline to 16 weeks.

Results
After 16 weeks, children who consumed OI had significant decreases in body weight z-score (decrease of 3.1%), percent body fat (decrease of 2.4%), and percent trunk fat (decrease of 3.8%) compared to children given placebo (increase of 0.5%, increase of
0.05%, and decrease of 0.3%, respectively). Children who consumed OI also had a significant reduction in level of interleukin 6 (IL6) from baseline (decrease of 15%) compared with the placebo group (increase in 25%). There was a significant decrease in
serum triglycerides (decrease of 19%) in the OI group. Quantitative PCR 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. In fecal samples, levels of primary bile acids increased in the placebo group but not in the OI group over the 16-week study period.

Conclusions
In a placebo-controlled, randomized trial, we found a prebiotic (OI) to selectively alter the intestinal microbiota and significantly reduce body weight z-score, percent body fat, percent trunk fat, and serum level of IL6 in children with overweight or
obesity. Clinicaltrials.gov no: NCT02125955.

Key words:
inulin-type fructans, pediatric obesity, BMI, adiposity
Abbreviations:
A:G (Android to gynoid fat ratio), ANCOVA (Analysis of covariance), ANOSIM (Analysis of similarities), BMI- body mass index (CA), cholic acid (CDCA), chenodeoxycholic acid (CRP), C-reactive protein (DXA), dual-energy x-ray absorptiometry (FBA), fecal
bile acid (HOMA2-IR), homeostatic model assessment for insulin resistance 2 (IBS), irritable bowel syndrome (IL), interleukin (LPS), lipopolysaccharide (NMDS), nonmetric multidimensional scaling (OI), oligofructose- enriched inulin (OTU), operational
taxonomic unit (qPCR), quantitative PCR (T2D- type 2 diabetes)
Grant Support This work was supported by grants from the BMO Financial Group Endowed Research Fund in Healthy Living, Alberta Children’s Hospital Foundation, Alberta Children’s Hospital Research Institute and the Canadian Institutes of Health
Research (MOP115076-1). These agencies had no role in study design, data collection, analysis, and interpretation, or manuscript preparation. ACN and MPH received scholarship funding from the Alberta Children’s Hospital Research Institute. ACN received
scholarship funding from the Canadian Institutes of Health Research. SM is funded through an Eyes High Postdoctoral Fellowship and an Alberta-Innovates Health Solutions Postdoctoral Fellowship.

Disclosures ACN, MPH, IM, SM and JW declare no conflict of interest. RAR previously held funding from Beneo, manufacturer of oligofructose-enriched inulin, for a project not related to the current work.

Author Contributions RAR conceived the study. ACN and MPH carried out the study and acquired the data. ACN, MPH, IM, SM and JW analysed and interpreted the data. ACN drafted the manuscript. ACN, IM, JW and RAR critically revised the manuscript for
important intellectual content. RAR received funding and had primary responsibility as the study supervisor.

© 2017 by the AGA Institute
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