Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• The colonic mucus gel layer (MGL) is crucial for excluding bacteria and maintaining intestinal homeostasis.
• Defects in the MGL are observed in ulcerative colitis (UC), allowing bacterial contact with the colonic surface.
• MUC2 is the primary mucin in healthy colons, while MUC5AC is induced in UC and protective in helminth infections.

Purpose of the Study:

• To investigate the expression and functional role of MUC5AC/Muc5ac in UC biopsies and a murine colitis model.
• To determine if MUC5AC/Muc5ac protects against colonic injury during inflammation.

Main Methods:

• MUC5AC/Muc5ac expression was measured in UC biopsies and DSS-induced colitis in mice.
• Muc5ac-deficient (Muc5ac-/-) mice were used to model the functional role of Muc5ac in colitis.
• Bacterial-epithelial interaction, translocation, and microbial composition were assessed, along with the effect of antibiotic treatment.

Main Results:

• Colonic MUC5AC/Muc5ac mRNA expression was significantly increased in active UC and murine colitis.
• Muc5ac-/- mice exhibited exacerbated injury and inflammation in DSS colitis, with increased bacterial contact and translocation.
• Antibiotic treatment ameliorated colitis severity in Muc5ac-/- mice, indicating a role for bacteria.

Conclusions:

• Induction of MUC5AC/Muc5ac in the inflamed colon mitigates injury by preventing bacterial breach of the MGL.
• MUC5AC plays a protective role in colitis by limiting bacterial translocation.