The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis
Open accessAbstract
Objective: The colonic inner mucus layer protects us from pathogens and commensal-induced inflammation, and has been shown to be defective in active UC. The aim of this study was to determine the underlying compositional alterations, their molecular background and potential contribution to UC pathogenesis. Design: In this single-centre case–control study, sigmoid colon biopsies were obtained from patients with UC with ongoing inflammation (n=36) or in remission (n=28), and from 47 patients without colonic disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analysed by nanoliquid chromatography-tandem mass spectrometry. Mucus penetrability and goblet cell responses to microbial stimulus were assessed in a subset of patients. Results: The core mucus proteome was found to consist of a small set of 29 secreted/transmembrane proteins. In active UC, major structural mucus components including the mucin MUC2 (p<0.0001) were reduced, also in non-inflamed segments. Active UC was associated with decreased numbers of sentinel goblet cells and attenuation of the goblet cell secretory response to microbial challenge. Abnormal penetrability of the inner mucus layer was observed in a subset of patients with UC (12/40; 30%). Proteomic alterations in penetrable mucus samples included a reduction of the SLC26A3 apical membrane anion exchanger, which supplies bicarbonate required for colonic mucin barrier formation. Conclusion: Core mucus structural components were reduced in active UC. These alterations were associated with attenuation of the goblet cell secretory response to microbial challenge, but occurred independent of local inflammation. Thus, mucus abnormalities are likely to contribute to UC pathogenesis.
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The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
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Cited by
Le Berre, C., Honap, S., & Peyrin-Biroulet, L. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00966-2 · Cited by 1,643
Gut barrier disruption and chronic disease
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Self-citationAn intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function
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Self-citationMUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis
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Metadata
- Authors
- van der Post, S., Jabbar, K. S., Birchenough, G., Arike, L., Akhtar, N., Sjovall, H., Johansson, M. E. V., & Hansson, G. C.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2019-03-26
- Volume
- 68
- Issue
- 12
- Pages
- 2142-2151
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2924306602
- Cited by
- 533
- References
- 36
- FWCI
- 24.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- van der Post, S., Jabbar, K. S., Birchenough, G., Arike, L., Akhtar, N., Sjovall, H., Johansson, M. E. V., & Hansson, G. C. (2019). Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut. https://doi.org/10.1136/gutjnl-2018-317571
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