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The Leaky Gut

The concept of a leaky gut or as it is more properly called, increased intestinal permeability, is a very important one for understanding why autoimmune reactions occur. The gut can be considered an area which is "outside" of the body and it contains various "foreign" elements such as bacteria and food proteins. It is critical that little if any of these foreign particles reach the circulatory systems(blood and lymph) because if they did they would cause major immune reactions. The gut wall is normally impermeable to large molecules(ie intact folded proteins) and only when a food protein is broken down into amino acids can the molecules pass through the gut wall. However when the gut wall is damaged larger molecules such as intact food proteins and bacterial products can pass through and set off immune reactions. In genetically susceptible people these foreign proteins can sometimes cause autoimmune reactions by either mimicking self proteins or mimicking viral agents which themselves mimic autoantigens. The bottom line is people with an autoimmune disease want to heal their intestinal wall such that it  prevents the passage of foreign proteins.

Below are some links to essays on the leaky gut and how to heal it.

Galland Article
AIA Newsletter

Medline Abstracts

Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability.

Dig Dis Sci 1996 Dec;41(12):2493-8

Yacyshyn B, Meddings J, Sadowski D, Bowen-Yacyshyn MB

Department of Medicine, University of Alberta, Edmonton, Canada.

Increased intestinal permeability and the CD45RO isoform expression of the leukocyte common antigen on peripheral blood CD20+ B cells are found in Crohn's disease. Others have observed that multiple sclerosis (MS) patients may have an increased risk of coacquisition of Crohn's disease. The aim of this study was to identify an association between these diseases using peripheral blood CD45 isoform expression and intestinal permeability in MS. Lactulose/mannitol permeability and peripheral blood CD20+ B cell CD45RO expression were defined in healthy controls, MS patients, and patients coincidentally affected by MS and Crohn's or MS and ulcerative colitis (UC). Five of 20 MS patients had increased intestinal permeability, a finding not previously reported. High levels of CD45RO were found on circulating CD20+ B cells from patients with MS. This has not been reported previously in MS and is found in very few other conditions. Eight patients with coincident MS and Crohn's disease or MS and UC were studied. Coincident MS and UC patients expressed CD45RO on CD20+ B cells, a finding not identified in UC patients alone. A subgroup of MS patients has increased intestinal permeability. These patients express CD45RO CD20+ B cells, also found in Crohn's disease.

Gastrointestinal absorption of intact proteins.

Annu Rev Nutr 1988;8:329-50

Gardner ML

School of Biomedical Sciences, University of Bradford, West Yorkshire, England.

There is now no reasonable doubt that small quantities of intact proteins do cross the gastrointestinal tract in animals and adult humans, and that this is a physiologically normal process required for antigen sampling by subepithelial immune tissue in the gut. It is too small to be nutritionally significant in terms of gross acquisition of amino-nitrogen, but since it has important implications relating to dietary composition it must receive consideration from nutritionists. The process of intact protein absorption occurs without eliciting harmful consequences for most individuals, but it appears likely that a small number of people absorbing these "normal" amounts may react idiosyncratically; also, some individuals may absorb excessive amounts, and they may suffer clinically significant consequences. Likewise, individuals with diminished absorption of intact protein may be at risk. Normal absorption probably occurs predominantly by transcellular endocytosis with some possible contribution by a route between cells; increased net entry of protein to the circulation may reflect (a) increased paracellular (intercellular) passage, (b) increased transcellular passage, and/or (c) decreased lysosomal proteolysis. Tests to distinguish among these possibilities are strongly desirable. Intact protein absorption may be involved in the pathogenesis of inflammatory bowel disease, "food allergies, " and other diseases, including even major psychiatric disorders, but the current evidence is mainly indirect and suggestive. Great caution and careful objective studies are needed to establish whether such relationships with disease do exist and to unravel the underlying basic physiological mechanisms. Now that interest has developed in the assessment of intestinal permeability to small- and medium-sized molecules, it is hoped that equally simple methods for studying macromolecular permeability will be developed and applied. Therapeutic methods for enhancing intact polypeptide absorption would be valuable for vaccine and peptide drug administration by the oral route. Therapeutic reduction of the process may be relevant in food-sensitive patients.

Antigen absorption from the small intestine and gastrointestinal disease.

Pediatr Clin North Am 1975 Nov;22(4):731-46

Walker WA

In this article, I have attempted to summarize the concept of intestinal permeability to antigens such as ingested food proteins, bacterial breakdown products, endotoxins, and enzymes. The mature gut retains the capacity to absorb macromolecules by a pinocytotic mechanism which is more pronounced during the neonatal period. The vast majority of individuals have no ill effects from the intestinal transport of large molecules. However, when increased quantities of toxic or antigenic macromolecules gain access to the body because of a derangement in the intraluminal digestive process or because of a defect in the mucosal barrier, antigen absorption may be altered and result in either local intestinal or systemic disorders. The speculative concepts suggesting that clinical disease states may be associated with altered mucosal permeability have been discussed.

Review article: Intestinal permeability in Crohn's disease.

Aliment Pharmacol Ther 1997 Dec;11 Suppl 3:47-53; discussion 53-6

Meddings JB

Gastrointestinal Research Group, University of Calgary, Alberta, Canada.

Measurements of intestinal permeability (IP) may help in determining susceptibility for the development of Crohn's disease or imminent relapse in patients with the disease. It is now apparent that a subset of patients at high risk for the development of Crohn's disease have either increased baseline IP or an exaggerated response to environmental agents that increase IP. These, coupled with observations that increased IP in patients at risk for the development of Crohn's disease is associated with an abnormal immunological phenotype, lend support to the hypothesis that increased IP is a very early event in the genesis of Crohn's disease.

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