The gut barrier is maintained by intestinal lining cells and infection fighting cells. Good bacteria in the gut also help protect against leaky gut. A type of infection fighting cells called lymphocytes are the scouts at the surface that help in the protection against invaders and damage resulting in leaky gut.
Lymphocytes are seen in increased numbers near the surface of the intestinal lining in a variety of abnormal intestinal conditions, most notably celiac disease. Being close to intestinal epithelial cells, they are thought to perform several functions including tumor surveillance, restoration and repair of the lining, and fighting infection. Newer research indicates they are also crucial to maintaining the tight junctions between intestinal lining cells. This keeps the gut barrier intact, preventing the leaky gut syndrome. Intraepithelial lymphocytes (IEL’s) are important in maintaining the integrity of the tight junctions of gut to prevent the leaky gut syndrome.
Dalton et al. from the United Kingdom recently published data showing that in mice specialized intraepithelial lymphocytes help maintain the integrity of the epithelial cell barrier. Mice deficient in these IEL’s had severely compromised barrier function and were highly susceptible to infection from Toxoplasma and Salmonella typhimurium. Reconstitution IEL’s in deficient mice restored intestinal barrier and prevented infection.
In understanding the gut it is noteworthy that the gastrointestinal tract barrier consists of only one layer of intestinal lining cells. This single layer of cells, a type of epithelial cells, are the entry point for water and nutrients. They also act as a barrier to foreign proteins. This includes bacteria, viruses, toxic food proteins or lectins, noxious chemicals or other toxins, in what we eat or drink. In contrast to the gut, the skin, another barrier of the body to external invaders, has epithelial cells, but is multiple cells thick rather than a single layer.
In the gut, the long continuous single cell wall of epithelial cells joined tightly shoulder to shoulder, are the only barrier to entry from whatever is in the gut. If the barrier is damaged, foreign proteins in the gut may gain entry into the inside the body. This can result in serious infection, inflammation and/or activation of the immune system adversely. This can also result in various autoimmune diseases. I have posted a drawing of the normal intestinal villous and microscopic photos of the normal intestine and diseased intestine from celiac disease in my photo gallery. A slide showing increased IEL’s using special staining techniques is included. Images and accompanying explanations can be also be found on my website http://www.thefooddoc.com. The images will greatly help you to visualize the concept of the intestine lining and IEL’s.
Intestinal epithelial cells are joined together by tight junctions with the help of sophisticated proteins that include occludin and a regulatory protein zonulin. When held closely, the intestinal cells serve as a barrier to foreign proteins. When the gut barrier is breached, various foreign invaders such as infectious agents, toxins, chemicals or perceived foreign proteins can enter. Perceived foreign proteins that can enter include intact food proteins or lectins. They gain entry into our bodies via the loss of tight junctions that result in a leaky gut.
Various injuries to the single cell layer result in gaps in the barrier by loosening up the tight junctions (TJ’s) between the intestinal lining cells. These injuries include damage due to poor blood flow, medications like aspirin, ibuprofen or chemotherapy agents, infections, food allergy or intolerance, chemicals or additives in foods or drinks, alcohol, excesses of certain foods especially carbohydrates, altered gut bacteria levels (dysbiosis) and yeast overgrowth. After the gut is injured and the tight junctions are damaged, the leaky gut syndrome develops.
How important are intraepithelial lymphocytes in preventing the leaky gut syndrome? Dalton and co-workers make this statement in their discussion. “Diseases including cancer, diarrhea, inflammatory bowel disease, multiple sclerosis, diabetes, and allergic disorders are associated with disruption of TJ’s and alterations in the regulation of occludin”.
Earlier in their article they use the term “leaky” TJ complexes to describe how bacteria could infect mice deficient in the IEL’s necessary to maintain gut integrity. This article furthers our understanding on how the gut barrier is maintained and may be injured. The concept of the leaky gut as an entry way to the body for infection, toxins, and foreign food proteins resulting in infection, toxicity and/or autoimmune disease(s) is intriguing.
Dalton, JE et.al. Intraepithelial gamma delta lymphocytes maintain integrity of the intestinal epithelial tight junctions in response to infection. Gastroenterology 2006;131:818-829.
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