In high-income countries, the leading causes of death are non-communicable diseases, such as Inflammatory Bowel Disease (IBD), cancer and cardiovascular disease. An important feature of most non-communicable diseases is inflammation-induced gut dysbiosis characterized by a shift in the microbial community structure from obligate to facultative anaerobes such as Proteobacteria. This microbial imbalance can contribute to disease pathogenesis due to either a microbiota-derived metabolite being depleted or produced at a harmful concentration. However, little is known about the mechanism by which inflammation mediates changes in the host physiology to induce disruption of the microbial ecosystem in our large intestine leading to disease.
Our group uses a multidisciplinary approach combining microbiology, molecular biology, cell biology, immunology and pathology to try to understand how inflammation-dependent changes in gut epithelial metabolism can result in gut dysbiosis and increased risk to non- communicable disease. Specifically, we used a variety of mouse models, including diet-induced-obesity, chemical-induced colitis, infectious gastroenteritis (Salmonella enterica serovar Typhiumurium), and germ-free animals with the goal to identify metabolic pathways in the gut bacteria and in the host response to microbiota-induced metabolites that will aid in prevention of human disease.
- How do the host and the microbiota work together to promote health?
- What are the mechanisms leading to gut dysbiosis during inflammation?
- Can we identify the metabolic pathways in gut bacteria and in the host response to microbiota- produced metabolites that will aid in the prevention of human diseases?
- Can we prevent non-communicable diseases by targeting host epithelial metabolism?