Status: Funded - Open
Brynn O'Laughlin, MD
BACKGROUND: Childhood obesity is epidemic in the United States; approximately 20% of children have obesity and 2% have severe obesity. Bariatric (weight loss) surgery is highly successful in enabling weight loss and decreasing associated comorbidities (heart disease, liver disease, diabetes), although the biological mechanisms underlying the success of bariatric surgery are not fully elucidated. GAP: The gut microbiota (community of microorganisms in the intestines) appears to provide bacterial control of metabolic processes that could impact energy regulation in obesity, but its role has not been determined in children undergoing laparoscopic vertical sleeve gastrectomy (VSG); this would be the first prospective longitudinal study to do so. It is important to study this group as the developing microbiome of a child differs from an adult and plays a clearer role in establishing metabolic pathways. HYPOTHESIS: Hypothesis 1: We hypothesize that most children and adolescents who undergo VSG will develop a more favorable stool microbiota profile with a decrease in proinflammatory bacteria that will be sustained 6 months post-surgery. Hypothesis 2: We hypothesize that the function of the microbiome will change after VSG, with a change in key metabolites associated with host energy harvesting such as short chain fatty acids. METHODS: We will collect stool, blood, and urine serially in combination with clinical data at four points spanning from prior to surgery to up to 6 months post-surgery of children and adolescents undergoing VSG at our institution. We will perform shotgun metagenomic sequencing (deep microbiome sequencing) on stool samples to compare differences in microbiome diversity, composition, and taxa down to the strain level over time in addition to untargeted metabolomics via mass-spectrometry. RESULTS: Pending. IMPACT: Understanding these microbiome changes will further expound the pathophysiology of pediatric obesity and the success of weight loss surgery, by characterizing the functional role of the microbiome during rapid weight loss after VSG. This will generate preliminary data for the development of microbiome-based therapeutics for the treatment of childhood obesity.