Table I.

Associations of representative diseases and disease models with intestinal barrier loss

	Inflammatory Bowel Disease	Celiac Disease	Graft vs. Host Disease	Type I Diabetes Mellitus
Structural alterations
Pore pathway	Increased claudin-2 expression45,47,60,85	Increased claudin-2 expression119,120,162	Increased claudin-2 expression139
Leak pathway	Reduced occludin expression47; increased MLCK expression and activity58,60,86, MLCK inactivation reduces severity60	Reduced occludin expression104,119	Reduced occludin expression163
Unrestricted pathway	Ulceration, epithelial apoptosis60,135,164		Epithelial apoptosis165
Functional alterations
Pore and/or leak pathways	Increased lactulose:mannitol ratio and PEG-400 permeability in disease,82,83,166–168 impending relapse,87–89,169 and some healthy relatives92,93,170	Increased lactulose:mannitol ratio in disease82,96,171	Increased sucralose permeability137	Increased lactulose:mannitol ratio141,142,172
Leak and/or unrestricted pathways	Increased 4kD dextran and Evan’s blue flux in DSS-induced colitis135,173,174	Pathogenic bacterial that increase intestinal permeability accelerate disease175	Development of experimental minor mismatch disease requires intestinal damage 139, the extent of barrier loss induced by pre- transplant conditioning correlates with disease severity176