Increased frequency of inflammatory bowel disease: the cost of reducing the incidence of infections?
Bacteria and parasites play a non-specific protective role in inflammatory bowel disease, similar to that described in allergic and autoimmune diseases.
It cannot be said that inflammatory bowel disease (IBD) is prevalent worldwide, however, there is a tendency for their occurrence more common in developed countries compared to developing countries. The assumption of a lower level of diagnosis of these conditions in developing countries is valid, but it most likely only partially explains the difference. In various states of America and Europe, the prevalence of inflammatory bowel disease varies widely. Attempts have been made to determine what could explain these geographic differences. We should not forget about the genetic factors that may be important in the development of IBD, although this is not fully confirmed. The most obvious factor explaining the uneven geographic distribution of ITNs is the socio-economic level. Climatic and dietary factors may occur, but this is also not fully proven.
Cohort studies have documented that sanitation can play a major role, at least in the development of Crohn's disease, suggesting that a decrease in the incidence of infections leads to an increase in the incidence of inflammatory diseases. It is also interesting to note that in families with several children, inflammatory bowel disease occurs more often in the first child, who is not susceptible to infections transmitted by his siblings.
The results of scientific observations are very contradictory. Thus, when creating an experimental model of inflammatory bowel disease in rodents, it has been shown that the appearance of colitis can be prevented by the appointment of bacteria, bacterial extracts or helminths. Of particular interest is the administration of probiotics (live or killed) that protect against disease by acting on Toll-like receptors (TLR) type 9. The binding of components of the microbial wall to Toll-like receptors leads to the activation of the intracellular signaling system from the membrane to the nucleus and to the transcription of the cytokine response genes, which leads to the activation of phagocytes and d other immunocompetent cells. Thus, Toll-like receptors are key structures that recognize a variety of substances of microbial origin and trigger the expression of non-specific resistance factors.
The existing relationship between low infectious morbidity and an increased incidence of inflammatory bowel disease has been recorded in the study of spontaneous or experimentally induced allergic and autoimmune diseases in animal models.
As for the clinical level, there is speculation, but there is not yet sufficient evidence that the use of probiotics improves the course of inflammatory bowel disease.
Currently, two main mechanisms have been proposed to explain the protective role of infections in relation to immune disorders - competition and suppression.
Competition between anti-infectious immune system responses and other responses can be considered at the following levels: 1) competition for the antigen which is caused by phagocytes; 2) competition for the binding of antigenic peptides to the molecules of the main histocompatibility complex (HLA); 3) competition for the cytokines necessary for the differentiation and homeostasis of lymphocytes.
Suppressive mechanisms mainly include suppressive cytokines (IL-10 and transforming growth factor β - TGF-β), which play a major role in the activation of regulatory T lymphocytes, in particular when studying experimental models of colitis.
Thus, the experimental data indicate that bacteria and parasites play a non-specific protective role in IBD, similar to that described in allergic and autoimmune diseases (hygienic hypothesis). The mechanisms (including homeostatic regulation and TLR stimulation) underlying this phenomenon have not yet been fully studied, but these concepts do not exclude the possible development of the effect of the use of probiotics and TLR ligands.