Early Gut-Vascular Barrier Breakdown Precedes Colitis Onset in Murine Models.

Area of Science:

• Gastroenterology
• Medical Imaging
• Vascular Biology

Background:

• The gut-vascular barrier (GVB) is crucial in inflammatory bowel disease (IBD) pathogenesis.
• Early detection of vascular changes in IBD is challenging.

Purpose of the Study:

• Introduce a novel 3D multiphoton endomicroscopy (MPEM) approach.
• Enable real-time, sensitive detection of vascular permeability (VP) in the colon.
• Identify early colitis-associated vascular changes.

Main Methods:

• Utilized fluorescence-based MPEM for in vivo visualization of VP dynamics in experimental colitis models.
• Compared VP changes with conventional inflammatory markers and histopathology.
• Investigated molecular regulation of vascular (PV1, VE-cadherin) and epithelial (E-cadherin) barriers.

Main Results:

• MPEM provided unprecedented 3D visualization of VP dynamics.
• Vascular dysfunction occurred before epithelial barrier breakdown and traditional inflammatory markers.
• Early GVB disruption preceded mucosal barrier breakdown, confirmed at the molecular level.

Conclusions:

• 3D MPEM demonstrated GVB dysfunction in early experimental colitis.
• Early GVB disruption precedes mucosal barrier breakdown.
• MPEM-based VP analysis may improve IBD diagnosis and clinical decision-making.