Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis

Abstract

Many immune-based intestinal disorders, such as ulcerative colitis and Crohn's disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work-gut microbiota, immune system, and their influence in the neuroimmune system.

Figure 1

The functional interaction between microbiota and intestinal immune system. The evolutionary balance is formed over time, being modulated by the environmental pressure. Gut microbiota and gut environment are developed together, fitting for the benefit of both or tolerating each other. The immune system monitors the interaction to ensure homeostasis and contributes to symbiosis. However, the unbalance caused when dysbiosis is installed may cause the immune system reaction. Symbiosis and dysbiosis depend on balance between commensal and pathogenic bacteria. Commensal bacteria promote an anti-inflammatory environment. In a symbiosis context, MAMPs continuously stimulate IECs to secrete molecules that act protecting the epithelium and producing a tolerogenic environment. In dysbiosis, there is a significant liberation of MAMPs that can induce IECs, activated DCs, and macrophages to secrete inflammatory cytokines. Consequently, a development of immune effectors is generated. IL-22 is produced in both situations, but its contribution to epithelial barrier improvement is controlled by immune regulation. M: macrophage; Comm: commensal bacteria; Patho: pathogenic bacteria.