Journal Article

Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis

Olli, Kristine E, Goldberg, Matthew S, Robertson, Charles E, Frank, Daniel N, Evans, Christopher M, Jensen, Owen, Collins, Colm B, O’Connell, Lauren, Jedlicka, Paul, Rapp, Caroline, Ir, Diana, McNamee, Eoin N, Aherne, Carol M, Gerich, Mark E, Allison, Kristen C

2020

Overview

Recent studies highlight the importance of mucins, in particular Muc2, in intestinal homeostasis. Our functional study demonstrates that an alternative secreted mucin, MUC5AC/Muc5ac, is induced in colitis to protect the colonic barrier by limiting host-bacterial interaction.AbstractBackgroundThe 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.MethodsWe 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 bacterial-epithelial 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.ResultsColonic 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.ConclusionsMUC5AC/Muc5ac induction in the acutely inflamed colon controls injury by reducing bacterial breach of the MGL.

• Publisher: Oxford University Press
• Subject: Analysis / Animals / Antibiotics / Bacteria / Bacteria - genetics / Basic Science Research / Biopsy / Colitis - chemically induced / Colitis - genetics / Colitis - microbiology / Colitis, Ulcerative - genetics / Colitis, Ulcerative - microbiology / Colitis, Ulcerative - pathology / Colon - metabolism / Colon - microbiology / Dextran / Dextran Sulfate / Disease Models, Animal / Health aspects / Homeostasis / Humans / Inflammatory bowel disease / Intestinal Mucosa - metabolism / Intestinal Mucosa - microbiology / Lymphatic system / Mice / Mucin 5AC - metabolism / Mucins / Protective Factors / RNA / RNA, Ribosomal, 16S / Sulfates / Ulcerative colitis