Microbiota-human mucin interactions: the keystone steps for a healthy community

My overall objective is to define the basic interaction mechanisms between microbiota and human colonic mucins in health and disease. The human microbiota has a significant impact on human health and disease.

These bacteria colonize the colonic mucus layer that is mainly composed of mucin, a glycoprotein that is heavily O-glycosylated. Some gut bacteria possess the ability to bind and degrade mucin.

However, the mechanistic details of how commensal gut bacteria bind and degrade complex mucin glycoproteins and how these interactions relate to disease development remain poorly understood.In this project, I will combine my unique expertise in biochemical characterization of bacterial proteins, microbiology and mucus biology to: 1) define the degradation mechanisms of colonic O-glycans by Bacteroides; 2) determine how microbiota members cooperate to breakdown colonic mucins; and 3) identify key glycan binding proteins utilized by commensal bacteria to select their host.

Additionally, my access to large amounts of human colonic mucin creates the opportunity to understand the microbiota-host interactions in order to translate this research to improve human health.

By understanding the fundamental mechanisms by which the microbiota interacts with mucins I will identify the keystone steps for gut colonization with a healthy microbiota.

This knowledge can then be used to restore the microbiota communities in diseases such as inflammatory bowel disease, obesity and diabetes.