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Microbiota-mucin interactions in the human gut

Research group

Active research

Project owner

Institute of Biomedicine

Area

Health and medicine

Topic

Microbiology Structural Biology Biochemistry and Molecular Biology

Short description

In the healthy colon, the mucus layer creates a physical barrier that limits the contact between the microbiota and the host tissue to prevent inflammation. The mucus has long been considered a passive barrier, but recent studies have shown that this layer plays a key role in selecting the host microbiota community. The major component of the mucus layer is mucin, a glycoprotein that is heavily O-glycosylated. It is known that some gut bacteria interact with colonic mucins and alterations of both, microbiota composition and mucin glycosylation, have been implicated in disease development. The Luis’s research group aims to define how commensal gut bacteria binds and utilizes highly complex mucin glycoproteins and how these processes relate to disease development.

The human microbiota has a significant impact on human health and disease. In the healthy colon, the mucus layer forms a critical barrier that physically separates the microbiota from the intestinal epithelium preventing the occurrence of close contact and subsequent inflammation. Mucus is mainly composed of secreted mucins, which are glycoproteins decorated with over 100 different O-glycan structures that comprise up to 80% of their mass. The sugar and linkage diversity of mucin O-glycans present significant barriers to degradation by bacteria. However, some gut bacteria possess the ability to degrade mucin, and alterations of the mucus layer have been implicated in the development of inflammatory bowel disease, obesity and colorectal cancer.

Mucin glycosylation also affects the composition of the microbiota. In a healthy state, the O-glycans in mucins provide attachment points for binding proteins encoded by the commensal bacteria. These interactions between the bacteria and host mucin glycans are a key factor in the continuous repopulation of the gut by the microbiota and are likely to have a major impact on community composition in health and disease. However, it remains unclear which microbiota proteins bind to mucins and how commensal bacteria degrade and modify the glycans found in these glycoproteins.

My lab deploys a multidisciplinary approach in order to define how the microbiota members degrade and utilize colonic mucins and to identify key glycan binding proteins utilized by commensal bacteria to select their host. Additionally, we have multiple ongoing collaborations with national and international laboratories that share common research interests in protein biochemistry, anaerobic microbiology, glycobiology and mucin biology.

Our goal is to define the basic mechanisms of microbiota-host interactions in order to reveal bacterial proteins that are potential drug targets in diseases linked to alterations of mucus barrier.