Abstract
Pediatric obesity remains a public health burden and continues to increase in prevalence. The gut microbiota plays a causal role in obesity and is a promising thera-peutic target. Specifically, the microbial production of short-chain fatty acids (SCFA) from the fermentation of otherwise indigestible dietary carbohydrates may protect against pediatric obesity and metabolic syndrome. Still, it has not been demonstrated that therapies involving microbiota-targeting carbohydrates, known as prebiotics, will enhance gut bacterial SCFA production in children and adolescents with obesity (age, 10 to 18 years old). Here, we used an in vitro system to examine the SCFA production by fecal microbi-ota from 17 children with obesity when exposed to five different commercially available over-the-counter (OTC) prebiotic supplements. We found microbiota from all 17 patients actively metabolized most prebiotics. Still, supplements varied in their acidogenic poten-tial. Significant interdonor variation also existed in SCFA production, which 16S rRNA sequencing supported as being associated with differences in the host microbiota compo-sition. Last, we found that neither fecal SCFA concentration, microbiota SCFA production capacity, nor markers of obesity positively correlated with one another. Together, these in vitro findings suggest the hypothesis that OTC prebiotic supplements may be unequal in their ability to stimulate SCFA production in children and adolescents with obesity and that the most acidogenic prebiotic may differ across individuals. IMPORTANCE Pediatric obesity remains a major public health problem in the United States, where 17% of children and adolescents are obese, and rates of pediatric “severe obesity” are increasing. Children and adolescents with obesity face higher health risks, and noninvasive therapies for pediatric obesity often have limited success. The human gut microbiome has been implicated in adult obesity, and microbiota-directed therapies can aid weight loss in adults with obesity. However, less is known about the micro-biome in pediatric obesity, and microbiota-directed therapies are understudied in children and adolescents. Our research has two important findings: (i) dietary prebiotics (fi-ber) result in the microbiota from adolescents with obesity producing more SCFA, and (ii) the effectiveness of each prebiotic is donor dependent. Together, these findings suggest that prebiotic supplements could help children and adolescents with obesity, but that these therapies may not be “one size fits all.”.
Original language | English (US) |
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Article number | e00914-20 |
Pages (from-to) | 1-15 |
Number of pages | 15 |
Journal | mBio |
Volume | 11 |
Issue number | 4 |
DOIs | |
State | Published - Jul 1 2020 |
Funding
This study was supported in part by National Institutes of Health grants R24-DK110492 and 1R01DK116187, Translational Research Institute through Cooperative Agreement NNX16AO69A, the Damon Runyon Cancer Research Foundation, and the UNC CGIBD (NIDDK P30DK034987). This study used a high-performance computing facility partially supported by grant 2016-IDG-1013 (HARDAC+: Reproducible HPC for Next-Generation Genomics) from the North Carolina Biotechnology Center. This study was supported in part by National Institutes of Health grants R24-DK110492 and 1R01DK116187, Translational Research Institute through Cooperative Agreement NNX16AO69A, the Damon Runyon Cancer Research Foundation, and the UNC CGIBD (NIDDK P30DK034987). This study used a high-performance computing facility partially supported by grant 2016-IDG-1013 (HARDAC+: Reproducible HPC for Next-Generation Genomics) from the North Carolina Biotechnology Center. We thank Jessica McCann, Cameron Catherine, Charles Sarria, Alexandra Zizzi, and Janet Wooton for their contributions to this work. L.A.D. was a member of the Kaleido Biosciences Strategic Advisory Board and retains equity in the company.
Keywords
- Fermentation
- Microbiome
- Pediatric obesity
- Prebiotics
- Short-chain fatty acids
ASJC Scopus subject areas
- Microbiology
- Virology