Moreover, we discuss the challenges and perspectives of microbiome-targeted strategies in studying disease pathogenesis and developing new microbiome-related treatments. We highlight some of the existing mechanistic dissections of multifaceted microbiome-immunity dialogs in both homeostatic and diseased states. Here, we review and exemplify important current knowledge and key concepts linking the microbiome to development and function of the immune system. 13 The interactions between the gut microbiota and host immunity are complex, dynamic and context-dependent. In addition to regulation of infection and commensal spread, microbiome-immune interactions are implicated in a variety of ‘non-communicable’ gastrointestinal diseases including inflammatory bowel disease (IBD) 8 and celiac diseases, 9 as well as extra-intestinal disorders ranging from rheumatic arthritis, 10 metabolic syndrome, 11 neurodegenerative disorder 12 to malignancy. 6, 7 However, perturbation of the gut microbiome by environmental incursions (such as antibiotic use, diet or changes in geography), impairment of host-microbiome interfaces, or alterations of the immune system can result in systemic dissemination of commensal microorganism, susceptibility to pathogenic invasion, and aberrant immune responses. 5 Such intimate relationship requires the proper functioning of host immunity to prevent commensals from over-exploitation of host resources while maintaining immune tolerance to innocuous stimuli. From an ecological perspective, mammals and their commensal microorganisms co-evolved toward mutualism and hemostasis. The mammalian immune system encompasses a complex network of innate and adaptive components in all tissues, and plays a vital role in host defense against various potentially harmful external agents and endogenous perturbations of homeostasis. Recent advances in microbiome research revealed that the gut microbiome is not just a passive bystander, but actively impacts multiple host functions, including circadian rhythmicity, nutritional responses, metabolism and immunity. 1 The collective genomes of bacteria and other microorganisms in this ecosystem, including fungi, viruses, parasites, 2 have been increasingly investigated during the past two decades, facilitated by a rapid development of culture-independent genomic techniques.
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The human body, including the gut, skin and other mucosal environments, is colonized by a tremendous number of microorganisms, collectively termed the microbiome. We highlight aspects of the current knowledge, challenges and limitations in achieving causal understanding of host immune-microbiome interactions, as well as their impact on immune-mediated diseases, and discuss how these insights may translate towards future development of microbiome-targeted therapeutic interventions.
Here, we review features of microbiome-immunity crosstalk and their roles in health and disease, while providing examples of molecular mechanisms orchestrating these interactions in the intestine and extra-intestinal organs.
In a genetically susceptible host, imbalances in microbiota-immunity interactions under defined environmental contexts are believed to contribute to the pathogenesis of a multitude of immune-mediated disorders. The microbiome plays critical roles in the training and development of major components of the host’s innate and adaptive immune system, while the immune system orchestrates the maintenance of key features of host-microbe symbiosis. The interplay between the commensal microbiota and the mammalian immune system development and function includes multifold interactions in homeostasis and disease.
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