Who is really to blame for the complications associated with obesity?
Obesity and diabetes are at the top of the list of health risks. More than two billion people worldwide suffer from them, and more than three million people in the world die every year due to complications of obesity. Often, the harmful effects of obesity and diabetes do not stem from the excess weight per se, but from the side effects and associated diseases, such as fatty liver, as well as vascular diseases of the heart and peripheral arteries. In general, obesity and its complications greatly increase the tendency to be affected by inflammations and bacterial infections originating from the digestive system, or from inflammatory complications resulting from the "leakage" of bacterial products through the intestinal barrier into the sterile areas of the body. This exposure to bacteria and their products causes, over time, an aggravation of the obesity itself, and the worsening of the liver and heart diseases that accompany it. If we understand how obesity causes these side effects, we may be able to find ways to prevent the lives of overweight people from being put at risk.
A research group in the Department of Immunology at the Weizmann Institute of Science, headed by Prof. Eran Alinev, recently found an unexpected explanation for the link between obesity and the formation of side effects. The researchers discovered, in a study they conducted in overweight mice that were subjected to a diet designed to reduce their weight, that high levels of blood sugar are the decisive factor that damages the integrity of the intestinal barrier. When the barrier is damaged, intestinal bacteria can invade the bloodstream, thus increasing the risk of infections, or exposing the human body to bacterial products, so that people suffering from obesity, diabetes and their complications may suffer from persistent inflammation. This research Recently publishedin the scientific journal Science.
In a healthy person, there are several control mechanisms that ensure that the blood sugar levels will be kept normal within a very narrow range. Conversely, in patients with metabolic diseases, such as obesity and diabetes, there is often a chronic increase in the blood sugar level. The post-doctoral researcher, Dr. Christoph Theiss from Prof. Alinev's laboratory, who led the study, found that high levels of sugar in the bloodstream damage the function of the intestinal epithelial cells. These cells are arranged along the wall of the digestive tract in a layer that forms a thin barrier between areas The sterile body and the inner part of the intestines, where many commensal bacteria reside. The intestinal epithelial cells are entrusted with a task quite complicated - introducing food particles into the body, while preventing the entry of bacteria that could cause damage, and trapping them in the intestines. An advanced technology developed in collaboration with the research group of Prof. Benny Giger, also from the Weizmann Institute of Science, allowed the researchers to show that the intestinal epithelial cells "sense" their existence. of high sugar levels, this leads to the formation of significant changes in their genetic expression A rule between the body and the inner part of the intestine: the areas of close contact between the intestinal epithelial cells become permeable, and thus the intestinal bacteria and their products can penetrate into the bloodstream, causing inflammation and infections. In addition, the researchers discovered the key points through which the high sugar levels sabotage the functioning of the intestinal barrier These junctions prevented the tendency to infections and inflammations in animals suffering from obesity, diabetes, and metabolic complications.
Later in the study, the team also examined the relationship between high blood sugar and microbial invasion in humans. Blood tests were conducted on a group of volunteers, which included an analysis of sugar levels and the presence of bacteria-derived molecules in their blood. Similar to the findings of the tests in mice, here too a high correlation was found between high sugar levels as a chronic phenomenon, and the presence of bacterial products in the blood. On the other hand, no relationship was found between the signs of the presence of the bacteria and body weight or obesity. That is, compared to the importance and effect of high sugar levels, excess weight in itself has much less effect on intestinal permeability.
This study yielded a possible answer to the question, why obesity is so often accompanied by an increased risk of developing serious infections. He also points out that strict control of blood sugar may prevent the development of harmful side effects due to obesity. The research suggested possible treatment methods, such as blocking the sensing of the intestinal epithelial cells regarding high sugar levels, so that in the future it may be possible to control the infections and inflammations that develop in these patients. The scientists believe that the molecular explanations they found in this study can help to better understand other diseases related to defects in the functioning of the intestinal barrier, such as chronic hepatitis, food allergies and more.
