Axin1's mystique in manipulating microbiome amidst colitis

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Axin1 is traditionally known as a Wnt/β-catenin signaling regulator.
• The role of Axin1 in host-microbial interactions and its impact on gut homeostasis remained largely unexplored.

Purpose of the Study:

• To investigate the function of intestinal epithelial Axin1 in host-microbial interactions.
• To determine the effect of Axin1 deletion on colitis and gut microbiome composition.
• To elucidate the mechanisms by which Axin1 influences gut health and inflammation.

Main Methods:

• Utilized knockout mouse models with deletion of intestinal epithelial Axin1.
• Administered dextran sodium sulfate (DSS) to induce colitis.
• Analyzed gut microbiome composition, particularly Akkermansia muciniphila abundance.
• Assessed Wnt/β-catenin signaling, cell proliferation, migration, and goblet/Paneth cell morphology.

Main Results:

• Intestinal epithelial Axin1 deletion protected against DSS-induced colitis.
• Loss of Axin1 led to increased Wnt/β-catenin signaling, cell proliferation, and migration.
• Axin1 deletion specifically enriched Akkermansia muciniphila, which was identified as the protective factor against inflammation.
• Morphological changes in goblet and Paneth cells were observed, including altered Muc2 and lysozyme levels.

Conclusions:

• Intestinal epithelial Axin1 plays a critical role in regulating gut microbiome homeostasis and host defense against colitis.
• Targeting Axin1 in specific intestinal cells offers a potential therapeutic strategy for inflammatory bowel diseases.
• Axin1 influences innate immunity and microbial interactions, highlighting a novel link between Wnt signaling and gut microbiome modulation.