Chapter 5 – The Mucosal Microbiome: Imprinting the Immune System of the Intestinal Tract

The small intestine and colon house a complex ecosystem of bacteria, fungi, parasites, and viruses that together constitute the intestinal microbiome. This environment is in part shaped by historical exposure and diet, but it is also a consequence of host genetics and immune selection. The close interaction of host and commensals at the mucosal border poses a considerable challenge to the intestinal immune system. The microbial environment is constantly monitored through pattern recognition receptors. Signals from these receptors condition the cells of the mucosal immune system, including epithelial cells, in ways that profoundly affect host immune responses. The intestinal microbiome promotes innate immune activity and adaptive immune responses (e.g., Th17) that contain the intestinal microbiota and neutralize pathogens. At the same time, gut commensals are able to promote regulatory mechanisms that prevent inappropriate adaptive immune responses to nonpathogenic microbes. The human body is a complex ecosystem that harbors an incredible diversity of microorganisms on the skin and the mucosal surfaces of the gastrointestinal, respiratory, and genitourinary systems. Most of these microorganisms are located in the small and large intestines, comprising an estimated 1014 cells (10-fold greater than the number of human cells) The intestinal microbiota is in close proximity to the absorptive surface of the intestine, necessitating that the intestinal immune system discriminate the vast numbers of harmless or beneficial intestinal microbes from potential pathogens. This chapter will introduce the constituents of the intestinal microbiota, the factors that influence the microbiota, the various receptors that allow the immune system to sense microbial composition, and the mechanisms by which the microbiome can shape the intestinal immune system.