High blood sugar can lead to intestinal leakage and intestinal bacteria disorders

we've known for a long time that obesity, diabetes and metabolic syndrome are all associated with intestinal barrier dysfunction and changes in the composition of gut microbiotics. However, high blood sugar itself can also be the cause of intestinal dysfunction, resulting in a vicious circle.obesity, diabetes and metabolic syndrome have reached epidemic levels. Today, one person dies of diabetes every six seconds in the world, with nearly 130 million people with diabetes in our country, the highest in the world, and the total incidence of diabetes among adults is 12.8%, a "silent killer" that has seriously endangered people's health and put a heavy financial burden on society.blood sugar must be strictly controlled in order for the body to maintain physiological stability. Long-term high blood sugar levels can lead to many health problems, including kidney disease, neuropathy and cardiovascular disease. Studies have also shown that high blood sugar can also directly impair the function of the intestinal barrier, alter the intestinal bacteria, increase the susceptibility of intestinal infections. So what exactly did the study find?Lentin deficiency and excess body fat are not to blame We've long known that obesity is associated with increased intestinal permeability and bacterial product translocation into the bloodstream, but why this happens remains a mystery. Researchers at the Weizmann Institute of Science in Israel answered this question.first hypothesically, the lack of the satiety hormone leptin leads to dysfunction of the intestinal barrier. After all, mice with a lack of genetic leptin or a defective leptin are two common models of obese animals that exhibit impaired intestinal barrier function, increased susceptibility to intestinal infections, and increased microbial metabolites in the blood circulation. However, the specific absence of leptin receptors in intestinal cortectal cells does not produce the same barrier dysfunction or susceptibility to infection., they believe, may be that excess fat itself affects the function of the intestinal barrier. Previous studies have shown that feeding mice a high-fat, high-sugar diet can lead to weight gain and increase intestinal permeability and intestinal bacterial susceptibility. However, when researchers induced weight loss by limiting leptin-resistant food intake in mice, their intestinal barrier function did not improve, suggesting that excess body fat itself was not the cause of the effect on the gut., if it wasn't for leptin deficiency, it wasn't excess fat, what exactly was it? Obesity is often accompanied by poor glucose tolerance and high blood sugar. In fact, both the leptin deficiency model and the obese high-fat, high-sugar diet model are characterized by significant increases in blood sugar. So could high blood sugar levels be the cause of the harmful effects of obesity on the gut?High blood sugar causes intestinal leakage To test whether elevated blood sugar levels were involved in regulating the function of the intestinal barrier, the researchers induced high blood sugar in mice without obesity, using a drug called streptococcus, which destroys islet β cells in mice, resulting in a phenomosis very similar to type 1 diabetes in humans.streptococcus can cause dysfunction of tight connections between intestinal cortectal cells. When attacked by Bacillus citric acid, an intestinal pathogen, mice treated with streptococcus also showed more serious infections. This process is accompanied by a large number of citric acid bacteria growth, adhere to the intestinal cortical cells and the emergence of systemic changes. Restoring normal blood sugar levels with insulin therapy can improve its effects. All in all, this suggests that elevated blood sugar is in itself sufficient to cause intestinal permeability., is this going to happen to humans? The researchers recruited 27 healthy subjects to take some measurements. Glyinated hemoglobin (HbA1c), an indicator of a person's average blood sugar concentration over the past three months, is highly associated with biomarkers of intestinal bacterial transposing, which means increased intestinal permeability. However, other metabolic parameters, such as BMI, did not show a clear correlation.blocking intestinal cortical glucose metabolism restores intestinal barrier function what happens at the molecular level? To determine whether glucose directly affects the function of the intestinal cortectal cells, the researchers used in vitro cultured intestinal endocial cells to expose them to different concentrations of glucose. Glucose induces barrier dysfunction in a dose and time-dependent manner and leads to an overall change in the expression patterns of the endotent cell gene. More than 1,000 genes in intestinal cortical cells exposed to excess glucose are expressed differently, including some involved in metabolic pathways that are critical to maintaining the functioning of the intestinal barrier.interesting is that the use of 2-deoxyglucose competitively blocks glycolysis, inhibits glucose metabolism, and can completely save the intestinal barrier and immune function. It can also block the overall change in gene expression induced by streptococcus. Similarly, the selectivity of GLUT2, a glucose transporter in intestinal endotrine cells, causes mice to resist the destruction of the function of the intestinal barrier induced by streptococcus, increased susceptibility to infection, and changes in gene expression. Therefore, intestinal cortical cell ingestion and metabolism of glucose is necessary for barrier damage to occur.high-sugar diet has the same effectnot just for diabetics and insulin resistance patients, but also for those with healthy metabolism. It may affect intestinal cortectal cells in a similar way, leading to changes in dietaryly induced barrier function.normal, the glucose transport protein GLUT2 is located on the epithelyl cell substrate membrane, regulating glucose transport between epithelyl cells and the circulatory system. However, when the concentration of glucose in the small intestine cavity is too high, it also triggers GLUT2 to be inserted into the brush-like rim membrane of the intestinal cavity surface, facilitating the flow of glucose from the intestinal cavity to the cells. The more glucose is absorbed and metabolized, the greater the risk of intestinal leakage.high blood sugar can lead to intestinal bacteria disorders high blood sugar not only leads to intestinal leakage, but also related to changes in the gut bacteria. Significant changes were made in the intestinal bacteriocys of high-glucose mice, which could be corrected through insulin therapy and normal blood sugar levels.But, interestingly, this change in the gut microbiota does not appear to play a key role in the dysfunction of the intestinal barrier caused by high blood sugar, since transplanting the fecal cytosus of streptococcus-treated mice into sterile mice is not enough to cause bacterial susceptibility and increase susceptibility to infection. high blood sugar damage all mucous membrane barriers? effects of high blood sugar on epithelral barrier function may also be related to other mucous membrane barriers other than the gastrointestinal tract, such as the respiratory tract and skin. A study of nearly 70,000 diabetics showed a positive correlation between glycation hemoglobin values and various mucosa barrier functions and hospital-obtained infections. Glucose intake from the blood circulation occurs in a variety of different mucous membrane tissues, so it is possible that the same mechanism works in all mucous membrane barriers. intestinal leak and high blood sugar, which one appears first? know that intestinal leaks themselves can also cause inflammation, which can lead to high blood sugar, insulin resistance and weight gain. So, the question comes, "first there is chicken or first there is eggs", intestinal leakage and high blood sugar, which one appears first? honestly, we still don't know. It is possible that intestinal infections, exposure to environmental toxins, or immunogenic foods trigger the first destruction of the intestinal barrier, leading to bacterial susception and LPS-induced hyperglycemia. However, long-term intake of high-sugar diets and high-glycemic susceptible physiques can also trigger the first barrier damage, which can lead to bacterial susceptible and further metabolic damage. In fact, no matter which comes first, it is clear that high blood sugar can disrupt the function of the intestinal barrier, which in turn can lead to further metabolic damage, forming a vicious circle. We need to treat both intestinal and metabolic health to break this vicious cycle. If we focus only on curing the gut and not controlling blood sugar, we will continue to fight the disruption of the function of the intestinal barrier induced by high blood sugar; does this mean in practice? We know that impaired intestinal barrier function and changes in the intestinal bacteria, in addition to causing metabolic damage, can also have an impact on our overall physical and mental health; Therefore, in improving and maintaining intestinal health, we also need to consider balancing blood sugar. blood sugar regulation is essential to restore and maintain the integrity of the intestinal barrier. Reaching normal blood sugar levels through insulin therapy seems to improve all the harmful effects of high blood sugar on the gut, at least in mice. If this also applies to humans, then people with diabetes must use insulin to keep blood sugar levels under control, especially when trying to cure intestinal problems. In addition, people with diabetes should strictly control the intake of foods with high sugar index. blood sugar regulation should be considered when treating intestinal infections. High blood sugar reduces the host's defenses and increases the pathogen's susceptible to adhesion and infection to the intestinal cortification cells. Therefore, controlling blood sugar may also be a key part of supporting the intestinal immune system during and after treatment of intestinal infections. glucose in the diet may be as harmful to intestinal health as high blood sugar. A high-sugar diet can also lead to increased intestinal permeability and susceptibility to infection. increase in intestinal permeability cannot be entirely attributed to excessive fat intake. Numerous studies, especially in animals, have shown that a high-fat diet increases intestinal permeability, but a high-fat diet often also contains large amounts of sugar and refined carbohydrates, which, unsurprisingly, can lead to long-term elevated blood sugar. Of course, this is not to say that high fat is harmless, we need to pay attention to the balance between high-quality fatty acid intake and fatty acid intake. : Thais, C. A., et al. (2018). "Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection." Science 359(6382): 1376-1383.
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