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Original article
Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis
  1. Sjoerd van der Post1,
  2. Karolina S Jabbar1,2,
  3. George Birchenough1,
  4. Liisa Arike1,
  5. Noreen Akhtar1,
  6. Henrik Sjovall2,
  7. Malin E V Johansson1,
  8. Gunnar C Hansson1
  1. 1 Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden
  2. 2 Department of Gastroenterology, Sahlgrenska University Hospital, Gothenburg, Sweden
  1. Correspondence to Dr Gunnar C Hansson; gunnar.hansson{at}


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.

  • ulcerative colitis
  • mucins
  • mucosal barrier
  • mucosal protection
  • mucus

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  • SvdP and KSJ shared first author.

  • SvdP and KSJ contributed equally.

  • Contributors Design of studies: SvdP, KSJ, GB, MEVJ, GCH. Performance of experiments: SvdP, KSJ, GB, LA, NA. Clinical assessments: KSJ, HS. Writing of manuscript: SvdP, KSJ, GCH. All authors approved the manuscript.

  • Funding This work was supported by the National Institute of Allergy and Infectious Diseases (U01AI095473), Knut and Alice Wallenberg Foundation, European Research Council (ERC), Swedish Research Council, Swedish Cancer Foundation, IngaBritt and Arne Lundberg Foundation, Sahlgrenska University Hospital (ALF), Wilhelm and Martina Lundgren Foundation and Adlerbert Research Foundation.

  • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

  • Competing interests None declared.

  • Ethics approval The study protocol was approved by the regional ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it published Online First. The legend for figure 1 has been amended.

  • Patient consent for publication Not required.