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Why are some people so sensitive to gluten? The amazing connection between intestinal permeability and autoimmunity!
Intestinal permeability is a term that describes the process by which substances pass from the inside of the gastrointestinal tract through the cells that line the gut into the rest of the body. A healthy human gut possesses a certain level of permeability, which allows nutrients to pass through the gut while maintaining barrier function to prevent potentially harmful substances, such as antigens, from entering the body from the gut.
In the healthy human intestine, particles smaller than 4 Å can pass through tightly coupled claudin pores, and the spaces between cells can accommodate particles 10 to 15 Å.
The intestinal barrier is formed by the intestinal epithelium and separates the external environment (the contents of the intestinal lumen) from the body. The intestinal epithelium is mainly composed of one layer of cells and undertakes two important functions: first, to prevent the entry of harmful substances such as foreign antigens, toxins and microorganisms; second, to act as a selective filter to promote the absorption of nutrients, water and other nutrients in the diet. Absorption of beneficial substances.
This selective permeability is mainly mediated through two pathways:
- Transepithelial permeability: involves the specialized transport of solutes across epithelial cells.
- Paracellular permeability: Transport of substances through the gaps between epithelial cells.
Intestinal permeability is regulated by tight junctions between cells, and disruption of this barrier can be a trigger for the development of intestinal disease.
Regulation of intestinal permeability
One way in which intestinal permeability is regulated is through the CXCR3 receptor in intestinal epithelial cells, which responds to zonulin. A glycoprotein in gluten, gliadin, activates this signaling pathway, causing increased intestinal permeability in all people who eat gluten. This further results in macroscopic molecules entering the intestines more easily.
Intestinal perturbations, such as cholera, certain enteroviruses, parasitic infections, and high pressure, may alter the structure and function of intestinal tight junctions and may contribute to the development of chronic intestinal disease.
Clinical significance
Although most people experience no significant discomfort, the opening of tight junctions between cells (increased intestinal permeability) can be a trigger for disease affecting any organ or tissue. Enhanced intestinal permeability is associated with conditions such as celiac disease, irritable bowel syndrome, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, and allergic diseases.
In most cases, increased intestinal permeability precedes the development of disease, but the cause-and-effect relationship is unclear.
Taking celiac disease as an example, increased intestinal permeability seems to be caused by an abnormal immune response triggered by gluten, which allows the gliadin protein fragment to pass through the intestinal epithelium and trigger an immune response in the intestinal submucosa, thereby leading to a variety of gastrointestinal or non-intestinal diseases. Gastrointestinal symptoms.
Research direction
In normal physiology, glutamine plays a critical signaling role in enterocytes of the intestinal barrier, but whether glutamine supplementation is beneficial in the context of enhanced intestinal permeability remains unclear.
Some prebiotics and specific probiotics, such as E. coli Nissle 1917, have been shown to significantly reduce increased intestinal permeability. Studies have also shown that some drugs, such as Larazotide acetate, which acts as a zonulin receptor antagonist, can be used in combination with a gluten-free diet in the treatment of celiac disease to reduce gluten-induced intestinal permeability. Sexual enhancement.
Stress effects caused by exercise
Exercise-induced stress reduces intestinal barrier function. Human activity levels modulate the gut microbiome; increasing the intensity and total amount of exercise may lead to intestinal disruption, while supplementation may help maintain the diversity of the gut microbiome.
With the increasing awareness of human health, the correlation between intestinal permeability and various autoimmune diseases has attracted increasing attention. This topic is not only worthy of further discussion, but also an important aspect of today's diet and health management. But as research in this area deepens, will there be more specific guidance to improve intestinal permeability problems in the future?
