Chapter 10 - The Microbiota and Its Modulation in Immune-Mediated Disorders

Abstract

Bacteria, viruses, archaea, and fungi inhabiting the mucosal surfaces of the human body are collectively termed the microbiota, and have coevolved with the human body for millions of years. This has resulted in the development of diverse and extensive host–microbiota interactions, influencing multiple physiological processes, including metabolism and normal development and function of the immune system. The densest microbiota resides in the mammalian gastrointestinal (GI) tract, where it forms a diverse community of trillions of microorganisms, now believed to be an integral part of the human holobiome. While comprising only 1–3% of the total body mass, an individual’s gut microbiota cells and genes outnumber those of the human body’s cells by a ratio of up to 10:1 and 100:1, respectively. Bacterial composition varies along the GI tract, as each species colonizes a specific niche. Disruption of the microbial community, termed dysbiosis, is suggested to constitute a major risk factor for an increasing array of diseases, including susceptibility to common multifactorial disorders such as obesity and its complications, infection, auto-inflammation, metabolic homeostasis, and even cancer. In this chapter we will provide an overview of the establishment of the gut microbiota during human development, describe how it influences the establishment and normal functions of the host immune system, and the means by which we can control and alter its composition and function. We will then focus on a few examples demonstrating how dysbiotic microbiota composition and function may affect the pathogenesis of various immune-mediated disorders. The emerging data presented in this review suggests that interventions affecting microbiota functions and interactions with the host may be manipulated as future therapeutics targeting common immune-related disorders.