All because of germs
Scientists have explained the cause of diabetes
RIA Novosti, Vladislav Strekopytov
American biologists have found out that a protein produced by intestinal bacteria is responsible for the work of cells that synthesize insulin. Its deficiency can lead to diabetes. About what new functions of the microflora have recently been discovered by scientists — in the material of RIA Novosti.
The kingdom of microflora
The role of the intestinal microbiome is so important that it was even proposed to recognize it as an independent organ. However, from the point of view of biology, this is a community of microorganisms that exist in close symbiosis with humans.
According to scientists, the intestine contains about 50 trillion microorganisms — about 1.3 times more than the total number of cells in the body. The main part of the intestinal microflora is bacteria. There are also representatives of other taxa, such as yeast or fungi, but their role is very small.
Bacteria perform the most important tasks: they help to break down foods that are not otherwise absorbed by the body, participate in the synthesis of vitamins and amino acids, fight pathogens and poisons. In addition, in the process of vital activity, they secrete a special mucus that protects the intestinal walls from damage. Many biochemical processes are impossible without bacteria, and a violation of the balance of microflora leads to unpleasant consequences — from metabolic problems to mental illness.
Internal assistants
The inhabitants of the intestine collectively express an order of magnitude more genes than the entire human genome. Proteins and enzymes encoded by bacteria are involved in many processes, in some cases normalizing them, in others causing undesirable side effects. Biologists have only recently begun to study this aspect of microbiome activity.
First of all, scientists are interested in the role of bacteria in the biotransformation reactions that drugs undergo in the body. During this process, intermediates are formed, whose activity or toxicity depends on the state of the microflora.
"There are studies showing that the health of the microbiome largely determines the survival of cancer patients. Intestinal bacteria increase the effectiveness of chemotherapy and improve the general condition of patients, helping to cope with the symptoms of the disease and side effects of treatment," says the executive director of the ANO SIC "Healthy Nutrition" Candidate of Medical Sciences Svetlana Pavlichenko.
Trainer for the immune system
The role of the microbiome in maintaining immunity is especially great. Overcoming the intestinal barrier, bacteria enter the bloodstream and act as a natural vaccine: a normally functioning immune system remembers each new pathogen and forms specific antibodies against it for the future.
But the contacts of intestinal bacteria with the "defense forces" of the body do not always end well. If the immune defense is insufficient, inflammation, diseases of the liver, gastrointestinal tract and nervous system, obesity and cancer develop. And if it is excessive, there is a risk of autoimmune reactions.
To assess the overall activation of immune cells outside the gastrointestinal tract caused by the penetration of intestinal bacteria, American scientists proposed using the level of immunoglobulins G (Vujkovic-Cvijin et al., The systematic anti-microbiota IgG repertoire can identify gut bacteria that translocate across gut barrier surfaces // Science Translational Medicine, 2022). They make up about 75 percent of all antibodies in the blood plasma and actively react to bacterial infection.
Using the method of high-performance sequencing in combination with the determination of IgG, the authors established a list of intestinal bacteria, which are primarily targeted by the immune system of healthy people. Among them are bifidobacteria that normalize digestion, the Lachnospiraceae and Ruminococcaceae families that break down dietary fibers, as well as some other representatives of beneficial microflora.
A weapon against diabetes
The body needs insulin to regulate blood sugar levels. This hormone affects the metabolism in almost all tissues, and it is produced only by beta cells of the pancreas. With a decrease in their number or depletion, insulin secretion is disrupted, and this leads to diabetes mellitus.
At an early age, there is a short period when beta cells actively multiply. In most people, this process proceeds normally, but in some, the immune system suddenly begins to attack the emerging cell population, disrupting its ability to produce insulin in the proper volume. In this case, children develop type I diabetes.
Insulin is needed to provide glucose access to cells, where it is processed for energy. Without insulin, glucose accumulates in the blood, and cells are left without energy.
American scientists led by Jennifer Hill from the Institute of Molecular Biology at the University of Oregon have determined that the growth of the beta cell population occurs simultaneously with the diversification of microbial communities in the intestine, and people with type I diabetes tend to have a poorer intestinal microbiome. The conclusion is quite obvious — given the role of the microbiome in "training" the immune system and preventing autoimmune reactions. However, upon closer examination, it turned out that the connection between the microbiome and beta cells is much deeper.
In laboratory experiments, the authors found out that in danio fish deprived of intestinal microflora, the pancreas contains significantly fewer beta cells. Their replication, as the researchers found, is triggered at the early stages of development by the BefA protein produced by bacteria. Experiments on mice gave similar results. It is possible that children with type I diabetes do not have enough bacteria producing BefA in their intestines, scientists have suggested.
In a recent paper (Hill et al., BefA, a microbiota-secreted membrane disrupter, dissolves to the pancreas and increases β cell mass), Hill and her colleagues studied the protein structure in detail and described its properties. It turned out that BefA has the ability to destroy the membranes of many types of cells. But, surprisingly, the BefA attack causes beta cells to actively replicate - this was also a discovery.
"There are other examples in biology when disturbances in membranes are crucial for stimulating development," Jennifer Hill said in a press release from the University of Oregon, "But in this case we do not yet know exactly how damage causes cell replication here. We think that beta cells have some kind of special sensitization that allows them to respond to signals related to membrane permeability."
The BefA protein, produced by intestinal bacteria, enters the pancreas and triggers the replication of beta cells that produce insulin. Figure from the article by Hill et al.
Scientists have tested a mutated version of BefA, which is not able to affect cell membranes. It did not affect the production of beta cells, which once again indicates that active replication is associated with damage to the membranes.
The authors emphasize the crucial role of a healthy microbiome in creating a population of cells in early childhood, which will then produce insulin throughout life. The main causes of microflora disorders, they call the excessive use of antibiotics and artificial formula for feeding.
The researchers hope that their discovery will help create a BefA protein-enriched drug that will prevent children from developing type one diabetes.
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