Short-chain fatty acid production by gut microbiota from children with obesity is linked to bacterial community composition and prebiotic choice

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 therapeutic 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 10-18). Here, we used an in vitro system to examine the SCFA production by fecal microbiota 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 potential. Significant inter-donor variation also existed in SCFA production, which 16S rRNA sequencing supported as being associated with differences in the host microbiota composition. 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. IMPORTANCEPediatric obesity remains a major public health problem in the US, 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 non-invasive 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 microbiome in pediatric obesity, and microbiota-directed therapies are understudied in children and adolescents. Our research has two important findings: 1) dietary prebiotics (fiber) cause the microbiota from adolescents with obesity to produce more SCFA, and 2) 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.