Mucosal healing progression after acute colitis in mice

Area of Science:

• Gastroenterology and Immunology
• Cellular Biology
• Microbiome Research

Background:

• Mucosal healing is crucial for stable remission in inflammatory bowel diseases (IBD).
• Complex cellular processes like migration, proliferation, and differentiation drive healing.
• The sequence of colon mucosal repair events and luminal changes post-colitis is poorly understood.

Purpose of the Study:

• To investigate colon mucosal characteristics during healing in a chemically-induced colitis mouse model.
• To document the temporal evolution of epithelial repair and luminal environment during colitis resolution.

Main Methods:

• Dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice.
• Analysis of colonic luminal environment and epithelial repair at multiple time points post-DSS.
• Histomorphology, permeability tests, gene expression of repair factors, and 16S rRNA sequencing of microbiota.

Main Results:

• Maximal colitis severity correlated with barrier dysfunction and goblet cell depletion.
• Epithelial repair initiated early during inflammation, with upregulation of key factors (TGF-β, IL-15, IL-22, IL-33, Serum Amyloid A).
• Luminal alterations (hyperosmolarity, dysbiosis, low SCFAs) and mucosal abnormalities persisted despite diminishing inflammation.

Conclusions:

• Colon repair can commence during active inflammation and altered luminal conditions.
• Key molecular modulators play a longitudinal role in mucosal healing.
• Persistent luminal and mucosal abnormalities highlight the complexity of full recovery post-colitis.