Obesity and associated comorbidities, including type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH) are a global public health concern affecting >500 million adults, and the prevalence of obesity has more than doubled in the last several decades. The intestinal microbiota composition differs between obese and lean individuals but specific species have not been consistently associated the obese phenotype. Our overall hypothesis is that a continuum of disrupted, dysbiotic configurations of intestinal microbiota is related to obesity, and specific configurations affect progression of various comorbidities associated with metabolic syndrome.
We are exploring this hypothesis through a variety of studies:
- Characterization of the obese microbiome from a large number of individuals. We are working with Dr. Alex Khoruts and the Microbiota Therapeutics Program to enroll volunteers and characterize the myriad assemblages associated with the obese phenotype.
- Secondary analyses from cohort studies and crowd-funded databases. We are proposing to perform secondary analyses using available data from previous studies to increase our sample size and account for differences due to geography, race and ethnicity, sex, etc.
- Humanized mouse models for obesity. We are humanizing mice with gut microbiota from obese and lean donors to demonstrate the role of the microbiota in driving phenotype and investigating the mechanisms by which this occurs.
- Pediatric obesity. We are partnering with investigators from the Center for Pediatric Obesity Medicine to characterize the gut microbiota in children suffering from obesity to identify microbiota-based targets for intervention.