Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Intestinal Mucus Layer: Our Knight in Slimy Armor
2.1. Mucus Layer Structure and Composition
2.2. Mucus Layer Function
3. The Mucin Glycocode: Facilitator of Microbe–Mucus Interactions
3.1. Mucin Glycans as a Bacterial Attachment Site
3.2. Mucin Glycans as a Bacterial Energy Source
4. The Microbiota as a Modulator of Intestinal Mucus
5. The Microbe–Mucus Interface in CRC
Pathology | Mucus Characteristics | Experimental Evidence |
---|---|---|
IBD | Compromised structure and increased bacterial penetration of mucus layer | Muc2−/− mice develop spontaneous colitis [81]. |
Murine colitis models and UC patients show increased bacterial penetration [83,84]. | ||
Altered mucin glycosylation | Smaller, less complex glycans in active UC [85]. | |
Aberrant mucin secretion | Intestinal Xbp1 knockout mice display spontaneous enteritis, increased susceptibility to colitis, goblet cell deficiency, and aberrant mucin secretion [103]. See also [83,84]. | |
Accumulation of the MUC2 precursor | Mutant Muc2 gene (Winnie and Eeyore) mice develop inflammation and MUC2 precursor accumulation. UC patients (inflamed and non-inflamed) accumulate the MUC2 precursor [102]. | |
CAC/CRC | Aberrant mucus layer and increased mucus layer penetration | Muc2−/− mice develop spontaneous CRC [80]. |
Increased tumor predisposition in mice defective in the secretory cell lineage differentiation transcription factor atonal homolog 1 (Atoh1) [79]. | ||
nATF6IEC mice develop spontaneous colonic tumors and show a microbiota-dependent mucin-filled goblet cell loss and increased bacterial penetration [105]. | ||
Atypical glycosylation | Altered mucin O-glycan structures including, for example, changes in core glycan structures and Tn antigens [91,92]. | |
Altered mucin expression and atypical extracellular mucin expression | Abnormal subcellular distribution, de novo expression, and overexpression of mucins [88,89,90]. | |
Mucus completely surrounds cancer cells [96,97,98]. | ||
Bacterial biofilm formation and bacteria-induced mucus alteration | Bacterial biofilms contribute to CRC, e.g., carcinogenic subtypes pks+ E. coli and enterotoxigenic Bacteroides fragilis cooperatively induce tumors in co-colonized mice. The reduction of the mucus layer by ETBF allowed pks+ E. coli to come into close proximity with the intestinal epithelium [99,100,101]. | |
Increase in the mucin-degrading specialist A. muciniphila [93,94]. |
6. Experimental Models to Investigate Microbe–Mucus Interactions in the Intestine
7. Conclusions and Treatment Potential
Author Contributions
Funding
Conflicts of Interest
References
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Coleman, O.I.; Haller, D. Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer. Cancers 2021, 13, 616. https://doi.org/10.3390/cancers13040616
Coleman OI, Haller D. Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer. Cancers. 2021; 13(4):616. https://doi.org/10.3390/cancers13040616
Chicago/Turabian StyleColeman, Olivia I., and Dirk Haller. 2021. "Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer" Cancers 13, no. 4: 616. https://doi.org/10.3390/cancers13040616