ANA SOFIA LUÍS

The human microbiota has a key role in human health by priming the immune system, preventing the invasion by pathogens and, degrading complex polysaccharides present in our diet that would be otherwise inaccessible. In the colon, the microbiota colonizes the mucus layer that separates these bacteria and the intestinal epithelium preventing occurrence of close contact and subsequent 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. Previous studies show that some gut bacteria can bind to and degrade mucin O-glycans. Interestingly, alterations of both microbiota composition and human mucin glycosylation have been implicated in multiple diseases, such as, inflammatory bowel diseases (IBD), obesity and colorectal cancer. However, the link between microbiota and mucus is less well understood. It is therefore essential to understand how the human microbiota interact with and modify mucins, the major component of the mucus layer, if we are to develop novel treatments to promote microbiota and mucosal health.

In this project, Ana Sofia will determine how the microbiota members cooperate to degrade human mucins and the key bacterial enzymes in this process. This research can reveal bacterial proteins that are potential drug targets in diseases linked to alterations of mucus barrier. Additionally, by identifying bacterial proteins that bind mucin O-glycans, this project will also reveal how the gut microbiota colonizes the mucus layer. This will establish the fundamental concepts of how host O-glycan modifications can lead to shifts in microbiota composition and disease development.

Overall, by understanding the fundamental mechanisms by which the microbiota interacts with mucins this project will lead to the identification of key steps for gut colonization by a healthy microbiota. This knowledge can then be used to restore the microbiota communities in diseases such as IBD, obesity and colorectal cancer.