Microbiome and Mucosal Immunity in the Intestinal Tract

Abstract

The human bowel is exposed to numerous biotic and abiotic external noxious agents. Accordingly, the digestive tract is frequently involved in malfunctions within the organism. Together with the commensal intestinal flora, it regulates the immunological balance between inflammatory defense processes and immune tolerance. Pathological changes in this system often cause chronic inflammatory bowel diseases including Crohn's disease and ulcerative colitis. This review article highlights the complex interaction between commensal microorganisms, the intestinal microbiome, and the intestinal epithelium-localized local immune system. The main functions of the human intestinal microbiome include (i) protection against pathogenic microbial colonization, (ii) maintenance of the barrier function of the intestinal epithelium, (iii) degradation and absorption of nutrients and (iv) active regulation of the intestinal immunity. The local intestinal immune system consists primarily of macrophages, antigen-presenting cells, and natural killer cells. These cells regulate the commensal intestinal microbiome and are in turn regulated by signaling factors of the epithelial cells and the microbiome. Deregulated immune responses play an important role and can lead to both reduced activity of the commensal microbiome and pathologically increased activity of harmful microorganisms. These aspects of chronic inflammatory bowel disease have become the focus of attention in recent years. It is therefore important to consider the immunological-microbial context in both the diagnosis and treatment of inflammatory bowel diseases. A promising holistic approach would include the most comprehensive possible diagnosis of the immune and microbiome status of the patient, both at the time of diagnostics and during therapy.

Keywords: Crohn’s disease; Mucosal immunology; chronic inflammatory bowel disease; inflammatory intestinal diseases; intestinal mucosa; review; ulcerative colitis.

Figure 1

The intestinal epithelium is the central barrier and regulator of nutrient absorption of the gastrointestinal tract. Cells of the epithelium are tightly connected to each other by tight junctions and other cellular structures and prevent the unregulated diffusion of low-molecular compounds. Towards the intestinal lumen there is a further compartment on the intestinal epithelium, the intestinal mucus layer. This layer contains the commensal microbiome of the intestine, which fulfills important physiological intestinal functions. Commensals reduce colonization with pathogenic bacteria and form an additional diffusion barrier due to their biomass. Furthermore, the microbiome metabolizes nutrients and makes them accessible to the human organism. Commensal bacteria are also able to absorb ions and synthesize essential factors, e.g. vitamins, which are supplied to the host metabolism. Finally, commensals and epithelial cells of the intestine interact with the cells of the local intestinal immune system. These are primarily macrophages, antigen-presenting cells (APC), and natural killer cells. Epithelial cells, immune cells and commensal bacteria regulate each other and determine physiological digestion, as well as the immunological defense against exogenous pathogens.