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Author Spotlight: Investigating the Effects of Compounds on Intestinal Tissue Using 3D Human Cell Line Models
Published on: September 1, 2023
MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn's disease
Elena Layunta1, Sofia Jäverfelt1, Fleur C van de Koolwijk1
1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Abstract:
Crohn's disease (CD) is the chronic inflammation of the terminal ileum and colon triggered by a dysregulated immune response to bacteria, but insights into specific molecular perturbations at the critical bacteria-epithelium interface are limited. Here, we report that the membrane mucin MUC17 protected small intestinal enterocytes against commensal and pathogenic bacteria. In noninflamed CD ileum, reduced MUC17 levels and a compromised glycocalyx barrier allowed recurrent bacterial contact with enterocytes. Muc17 deletion in mice rendered the small intestine particularly prone to atypical bacterial infection while maintaining resistance to colitis. The loss of Muc17 resulted in spontaneous deterioration of epithelial homeostasis and in the extraintestinal translocation of bacteria. Finally, Muc17-deficient mice harbored specific small intestinal bacterial taxa observed in patients with CD. Our findings highlight MUC17 as an essential region-specific line of defense in the small intestine with relevance for early epithelial defects in CD.
Insights
The membrane mucin MUC17 protects the small intestine from bacteria. Reduced MUC17 in Crohn
Area of Science:
- Gastroenterology and Immunology
- Epithelial Biology
- Microbiome Research
Background:
- Crohn's disease (CD) involves chronic inflammation of the ileum and colon due to immune dysregulation against gut bacteria.
- Specific molecular defects at the bacteria-epithelium interface in CD remain incompletely understood.
- The role of intestinal mucins in maintaining epithelial barrier function and host-microbe interactions requires further elucidation.
Purpose of the Study:
- To investigate the role of the membrane mucin MUC17 in protecting small intestinal enterocytes.
- To determine if MUC17 alterations are associated with early epithelial defects in Crohn's disease.
- To explore the impact of MUC17 deficiency on intestinal homeostasis and host-microbe interactions.
Main Methods:
- Analysis of MUC17 expression in human Crohn's disease ileum.
- Generation and characterization of Muc17-deficient mice.
- Assessment of small intestinal barrier function, bacterial translocation, and epithelial homeostasis in wild-type and Muc17-deficient mice.
- 16S rRNA gene sequencing to profile the gut microbiota.
Main Results:
- Reduced MUC17 levels were observed in noninflamed Crohn's disease ileum, correlating with a compromised glycocalyx barrier and increased bacterial contact.
- Muc17 deletion in mice led to increased susceptibility to atypical bacterial infections in the small intestine but maintained resistance to colitis.
- Loss of Muc17 resulted in impaired epithelial homeostasis, spontaneous extraintestinal bacterial translocation, and a distinct small intestinal bacterial composition mirroring that found in CD patients.
Conclusions:
- MUC17 serves as a crucial, region-specific defense mechanism in the small intestine against bacterial invasion.
- Decreased MUC17 expression may represent an early epithelial defect contributing to the pathogenesis of Crohn's disease.
- Targeting MUC17 or restoring its function could offer novel therapeutic strategies for Crohn's disease.
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