Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis
Open Access
- 1 September 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in Inflammatory Bowel Diseases
- Vol. 26 (9), 1353-1367
- https://doi.org/10.1093/ibd/izaa064
Abstract
Background: The mucus gel layer (MGL) lining the colon is integral to exclusion of bacteria and maintaining intestinal homeostasis in health and disease. Some MGL defects allowing bacteria to directly contact the colonic surface are commonly observed in ulcerative colitis (UC). The major macromolecular component of the colonic MGL is the secreted gel-forming mucin MUC2, whose expression is essential for homeostasis in health. In UC, another gel-forming mucin, MUC5AC, is induced. In mice, Muc5ac is protective during intestinal helminth infection. Here we tested the expression and functional role of MUC5AC/Muc5ac in UC biopsies and murine colitis. Methods: We measured MUC5AC/Muc5ac expression in UC biopsies and in dextran sulfate sodium (DSS) colitis. We performed DSS colitis in mice deficient in Muc5ac (Muc5ac(-/-)) to model the potential functional role of Muc5ac in colitis. To assess MGL integrity, we quantified bacterialepithelial interaction and translocation to mesenteric lymph nodes. Antibiotic treatment and 16S rRNA gene sequencing were performed to directly investigate the role of bacteria in murine colitis. Results: Colonic MUC5AC/Muc5ac mRNA expression increased significantly in active UC and murine colitis. Muc5ac(-/-) mice experienced worsened injury and inflammation in DSS colitis compared with control mice. This result was associated with increased bacterial-epithelial contact and translocation to the mesenteric lymph nodes. However, no change in microbial abundance or community composition was noted. Antibiotic treatment normalized colitis severity in Muc5ac(-/-) mice to that of antibiotic-treated control mice. Conclusions: MUC5AC/Muc5ac induction in the acutely inflamed colon controls injury by reducing bacterial breach of the MGL.Funding Information
- National Institutes of Health (K01-DK099485, R03-DK114545, R01-DK111856, R01-HL130938, R01-HL080396)
- Crohn's and Colitis Foundation (276536, 601121)
This publication has 80 references indexed in Scilit:
- SINA: Accurate high-throughput multiple sequence alignment of ribosomal RNA genesBioinformatics, 2012
- Fast gapped-read alignment with Bowtie 2Nature Methods, 2012
- Dextran Sodium Sulfate Inhibition of Real-Time Polymerase Chain Reaction Amplification: A Poly-A Purification SolutionInflammatory Bowel Diseases, 2012
- Commensal Bacteroides Species Induce Colitis in Host-Genotype-Specific Fashion in a Mouse Model of Inflammatory Bowel DiseaseCell Host & Microbe, 2011
- Muc5ac: a critical component mediating the rejection of enteric nematodesThe Journal of Experimental Medicine, 2011
- The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactionsProceedings of the National Academy of Sciences of the United States of America, 2011
- Mucin Gene Deficiency in Mice Impairs Host Resistance to an Enteric Parasitic InfectionGastroenterology, 2010
- Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasisMucosal Immunology, 2010
- Distinct Cytokine Patterns Identified from Multiplex Profiles of Murine DSS and TNBS-Induced ColitisInflammatory Bowel Diseases, 2009
- Abnormal expression of M1/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancerInternational Journal of Cancer, 2007