Disruption of Mucin Glycosylation and Mucus Barrier Function in Response to a Western-Style Diet

In the healthy intestines, mucus acts as a barrier that separates the host epithelium from the microbiota and intestinal contents, as well as a habitat for commensal microbes. The major component of intestinal mucus, MUC2, is heavily O-glycosylated. Mucin O-glycans are critical for mucus barrier function and host-microbe interactions.

Alterations to mucin glycosylation have been associated with diseases such as inflammatory bowel disease and cancer, and represent a novel target for therapeutic intervention.

However, studies of the specific glycan structures altered during disease, as well as the consequences of these alterations on mucus barrier function and the microbiota, have been limited by a lack of tools to detect individual glycan epitopes.

Mucus barrier dysfunction and microbiota dysbiosis, specifically a shift towards expansion of mucin-degrading bacteria, have been observed in response to a high fat/sugar, low fiber western-style diet (WSD). My preliminary data indicates that a WSD can also alter specific mucin glycosylation patterns.

The identification of specific glycan alterations associated with a WSD creates the opportunity to study the role of individual glycan structures in mucus barrier dysfunction and microbiota composition.

This study aims to 1) develop novel probes to detect specific glycan epitopes and 2) use these probes to investigate the relationships linking mucus barrier dysfunction, glycan alterations, and dysbiosis in response to a WSD.

I will combine my previous experience characterizing glycan alterations in in vivo models of intestinal disease with host lab training in mucus physiology and bacterial enzyme characterization.

Findings will advance our understanding of how glycosylation patterns are altered during disease, and how these alterations contribute to disease pathogenesis.

This grant will allow me to enhance my skills as a researcher and give me the tools and experience necessary to establish my independent research group.