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Secret passages in the gut: What allows small molecules to cross the intestinal wall?
Intestinal permeability refers to the process by which substances pass from the digestive tract into the cells of the intestinal wall and then into the rest of the body. Under normal circumstances, the intestine has a certain degree of permeability, which allows nutrients to enter the blood through the intestinal wall, while also maintaining a barrier function to prevent potentially harmful substances (such as antigens) from entering the body along the intestine. In the healthy human intestine, small particles with a radius less than 4 Å can pass through the tightly coupled claudin pore channel, while particles up to 10–15 Å (3.5 kDa) in diameter are able to be taken up through the intercellular channel.
There is evidence that abnormally increased intestinal permeability may be associated with certain chronic diseases and inflammatory disorders.
In the physiological structure of the intestine, the barrier formed by the intestinal epithelium separates the external environment (the contents of the intestinal lumen) from the interior of the body, which is the most extensive and important mucosal surface of the human body. Intestinal mucus may also serve as a barrier to host antimicrobial peptides, thus playing a bidirectional barrier role in host-microbe interactions. The intestinal epithelium is composed of a single layer of cells and has two important functions: first, it acts as a barrier to prevent the entry of harmful substances such as foreign antigens, toxins and microorganisms; second, it acts as a selective filter to help absorb dietary nutrients from the intestinal cavity. , electrolytes, water and other beneficial substances.
Permeability and its regulation
Intestinal permeability is regulated primarily through two pathways: transepithelial permeability and paracellular permeability. Transport across epithelial cells primarily involves specialized transport proteins that are responsible for moving substances such as specific electrolytes, amino acids, sugars, and short-chain fatty acids into and out of the cell.
Specialized intestinal epithelial cells called microfold cells (M cells) can sample bacteria and their antigens in the intestinal lumen and endocytose them in a process called transcytosis.
Associated with the M cells are the subepithelial Peyer's patches, which are clusters of immune cells that recognize and respond to transcellular antigens. Normally this helps promote intestinal homeostasis, but certain bacterial pathogens such as Salmonella Typhimurium can induce the transformation of enterocytes into M cells, which may be a mechanism to facilitate bacterial invasion.
Gap permeability depends on intercellular transport and is mainly controlled by tight junctions of cells. This is the major passive flow pathway for water and solutes across the intestinal epithelium, and disruption of tight junctions may trigger intestinal diseases.
Clinical significanceWhile most people do not experience adverse symptoms, opening of tight junctions (enhanced intestinal permeability) may be a trigger for disease affecting any organ or tissue, depending on the individual's genetic predisposition. Increased intestinal permeability is a factor in several diseases such as celiac disease, irritable bowel syndrome, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, etc. In most cases, enhanced permeability precedes the development of disease, but the cause-effect relationship between enhanced intestinal permeability and disease is unclear in many diseases.
In celiac disease, increased intestinal permeability appears to occur secondary to an immune response to gluten, which allows gluten-induced protein fragments to pass through the intestinal epithelium, triggering gluten in the lower intestinal mucosa. Immune response.
Many environmental triggers may contribute to altered permeability in celiac disease, such as intestinal infection and iron deficiency. Once enhanced permeability is established, the inflammatory immune response may become self-sustaining and perpetuate a vicious cycle. When gluten is removed from the diet, intestinal permeability returns to normal and the autoimmune process is terminated.
Prospects and research
Under normal physiological conditions, glutamine plays a key signaling role in intestinal cells, but it is unclear whether glutamine supplementation helps enhance intestinal permeability. Certain prebiotics and probiotics, such as Escherichia coli Nissle 1917, have been found to reduce enhanced intestinal permeability. In addition, lactic acid bacteria, fermentative bacteria and Faecalibacterium prausnitzii also showed significant planning abilities. Larazotide acetate (formerly known as AT-1001) is an investigational zonulin receptor antagonist that has shown promise in clinical trials as a candidate for celiac disease patients, designed to reduce intestinal tract disturbances caused by gluten. Permeability and the resulting immune response chain reaction.
Effects of exercise on the intestinesExercise-induced stress can reduce the intestinal barrier function. The intensity of human exercise is closely related to the composition of the intestinal microbiota. Increased exercise intensity and volume may lead to intestinal disorders, while supplements can maintain the diversity of intestinal microorganisms. The experiment found that although exercise reduced the richness of microbial communities, it increased the distribution of bacterial communities.
With in-depth research on the relationship between intestinal permeability and various diseases, more effective prevention and treatment strategies may be developed in the future to improve intestinal health. How exactly does this affect our overall health?
