STRUCTURAL WEAKENING OF THE COLONIC MUCUS BARRIER IS AN EARLY EVENT IN ULCERATIVE COLITIS PATHOGENESIS
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ABSTRACT: The colonic inner mucus layer protects us from pathogen invasion and commensal-induced inflammation. Mucus abnormalities are common in ulcerative colitis (UC), but their cause and importance are unknown. The aim of this study was to determine the role of compositional mucus barrier alterations in UC. In this single-center case-control study, sigmoid colon biopsies were obtained from UC patients with ongoing inflammation (n=36) and in remission (n=28), and from 47 patients without inflammatory bowel disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analyzed by mass spectrometry. Mucus barrier integrity and goblet cell response to microbial challenge were also assessed for a subset of patients. The core colonic mucus proteome was shown to consist of a small set of 29 secreted proteins. Patients with active UC had reduced levels of major structural components, including the mucin MUC2 (p<0.0001), also in mucus from non-inflamed segments, and their goblet cell secretory response to microbial stimulus was abrogated. Functional mucus barrier failure was observed in a subset of UC patients with and without active inflammation, and accompanied by alterations in proteins associated with mucus secretion and luminal organization. This study represents the first characterization and comparison of the mucus proteomes of the inflamed and non-inflamed colon. Core mucus structural components were reduced in active UC, also in mucus from non-inflamed segments. Thus, weakening of the mucus barrier is likely to occur early in UC pathogenesis, and represents a novel target for intervention.
INSTRUMENT(S): LTQ Orbitrap
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: S.S van der Post
LAB HEAD: Gunnar C Hansson
PROVIDER: PXD012632 | Pride | 2021-03-26
REPOSITORIES: Pride
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