Thursday, June 6, 2013

Leaky Gut Syndrome - Celiac Disease - Crohn's Disease, and Colitis Linked to Altered Gut Permeabilit

Leaky gut syndrome:

Leaky gut syndrome is a term often used in complementary or alternative medicine circles and by the lay public that is really describing a known entity termed increased intestinal permeability. Gut permeability is important for health and prevention of disease. The intestine is lined with a single layer of epithelial cells, called enterocytes in the small bowel and colonocytes in the large bowel or colon. These epithelial cells both constitute the intestinal barrier and the digestive and absorptive lining of the gut.

Intestinal villous and microvilli increases absorptive area:

The small intestine lining has projections called villi that dramatically increase the surface area of the intestine. Each villous is lined with a single layer of enterocytes and goblet cells. The enterocytes of the small intestine have projections on their surfaces known as microvilli where digestive enzymes reside.

Tight junctions prevent leaky gut:

The cells are joined to each other by tight junctions or zonula occludens that form a barrier to fluid and proteins except when permitted by signals that open up the spaces between the cells, the paracellular space. Abnormal tight junctions result in increased intestinal permeability or what may be called a leaky gut. This altered intestinal permeability or barrier function is implicated in several diseases, especially celiac disease and the inflammatory bowel diseases ulcerative colitis and Crohn's disease.

Occludin, claudin and zonulin proteins:

Occludin and claudin are structural proteins that maintain the tight junctions or zonula occludens. These proteins are regulated at least in part by another protein, zonulin. The structure of the tight junctions is also known as a cytoskeleton.

Leaky gut can occur without visible or microscopic signs:

Obvious visually apparent defects of the lining of the intestine or mucosa such as ulcerations and erosions or atrophy are associated with increased intestinal permeability but ultra structural studies have shown that areas of the lining can have gaps in the intestinal barrier. That is, your gut can be leaky though it may look normal visually during endoscopy or even on plain microscope examination of biopsies.

Gluten can cause leaky gut without celiac disease:

Chronic gluten exposure has been shown to activate zonulin resulting in increased intestinal permeability (or leaky gut) even in the absence of celiac disease. Intestinal permeability with malabsorption has been described in celiac patients and their relatives who don't have atrophy of the intestine on biopsy but only increased inflammatory cells known as lymphocytes or increased intraepithelial lymphocytosis (IEL).

Lymphocytic enteritis may be the earliest microscopic sign of leaky gut:

Lymphocytic enteritis is a relatively new term for this small intestine biopsy finding. Since lymphocytes release chemical mediators such as tumor necrosis factor (TNF) it makes sense that increased numbers of lymphocytes in the villi releasing TNF can result in a leaky gut, malabsorption symptoms and increased risk of celiac disease, Crohn's, and colitis, especially in genetically predisposed individuals. Moreover, if altered gut bacteria and yeast levels are present the risks appear to be higher.

Tumor necrosis factor release results in leaky gut:

Interestingly, anti-tumor necrosis factor (anti-TNF) therapy in the form of remicade (infliximab) and humira (adalimubab) are highly effective in treating Crohn's disease, rheumatoid arthritis and more recently ulcerative colitis. Unfortunately, such therapy is directed at the already released TNF not the underlying cause or predisposition.

Probiotics may be protective against leaky gut and bowel inflammation:

Probiotics are gaining acceptance or interest in the prevention and treatment of both inflammatory bowel diseases (Crohn's and colitis) as well as irritable bowel syndrome (IBS). They are also being touted to prevent or treat antibiotic associated diarrhea.

Leaky gut gaining scientific support but bigger picture still being missed:

Again, however, it appears that there are a lot of researchers and physicians who appear to have some pieces of the bigger puzzle of leaky gut or altered gut permeability as a cause of intestinal diseases and intestinal and extra-intestinal symptoms but few are seeing the bigger picture. Go to to access the Food Doc Blog to explore this bigger picture and the latest research in the context of my experience of a practicing gastroenterologist who is also personally affected by food intolerance. Be sure to subscribe to the blog and e-mail postings to friends and family.


Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Drago, S et al. Scand J Gastroenterol. 2006; 41(4): 408-419

Inflammatory bowel disease: Is it really just another break in the wall? Weber, CR and Turner, JR. Gut 2007; 56(1): 6-8

Changes in expression and distribution of claudin 2,5, and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Zeissig S. et al. Gut 2007; 56(1): 61-72

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