Mission and Projects

Our laboratory uses synthetic microbial consortia to understand how gut microbes and diet modulate disease. hCom2 is a complex, defined microbial consortia comprised of 119 human gut bacterial strains that stably engraft within the mouse gut and largely recapitulate native fecal metabolic and immune function. Our projects use hCom2 to understand complex phenomena such as pathogen colonization resistance and collaborative metabolism of dietary and host molecules.

What are the major interactions between pathogens and commensal microbes? 

Known, significant microbe-microbe interactions are rare and the few that have been described have been hugely insightful toward understanding human health. Using hCom2 structural and genetic engineering, we are discovering novel microbiota-pathogen interactions that modulate pathogen colonization resistance.

How does the human diet modify pathogen invasion and colonization?

Diet is the most impactful factor shaping microbiota membership and dietary modulation could be an accessible, untapped route for pathogen preclusion.  Carriage of antibiotic resistant pathogens is rising in developed countries and a high fat, simple sugar ‘western diet’ is associated with decreased microbiota diversity.  Is our western diet simply more effectively consumed by pathogens or is it eliminating healthful commensals that would normally preclude pathogens? Using hCom2 colonized mice, we are identifying dietary molecules that impact colonization resistance and we anticipate that these substrates could one day, serve as basis for pre-biotic therapies, where food becomes medicine.

Can we rationally engineer the host metabolic pool?

Using community genetic engineering, we are building and testing synthetic consortia with programmable metabolic output. We are focused on engineering production of target metabolites such as bile acids and examining their impact on host physiology and gastrointestinal disease.

Developing microbial metabolic markers for disease

Significant microbiota and bio-fluid metabolite signatures exist in patient populations with liver fibrosis and inflammatory bowel disease. Our translational research platform aims to develop and validate and known and novel microbial metabolites as biomarkers for disease and disease progression.