Abstract
The human microbiome, often referred to as the ‘second genome’, encompasses up to 100-fold more genes than the host genome. In contrast to the human genome, the microbial genome is flexible and amenable to change during the host’s lifetime. As the composition of the microbial metagenome has been associated with the development of human disease, the mechanisms controlling the composition and function of the metagenome are of considerable interest and therapeutic potential. In the past few years, studies have revealed how the host immune system is involved in determining the microbial metagenome, and, in turn, how the microbiota regulates gene expression in the immune system. This species-specific bidirectional interaction is required for homeostatic health, whereas aberrations in the tightly controlled regulatory circuits that link the host immunogenome and the microbial metagenome drive susceptibility to common human diseases. Here, we summarize some of the major principles orchestrating this cross-talk between microbial and host genomes, with a special focus on the interaction between the intestinal immune system and the gut microbiome. Understanding the reciprocal genetic and epigenetic control between host and microbiota will be an important step towards the development of novel therapies against microbiome-driven diseases.
Highlights
The human microbiome, often referred to as the ‘second genome’, encompasses up to 100-fold more genes than the host genome
The findings indicate that several immune pathways contribute to maintaining a stable bacterial population, which potentially supports the existence of multiple levels of cross-talk, compensation, and complementarity in effector mechanisms of the innate immune system that exert control over the metagenome [75]
Deficiency in the NLRP6 inflammasome, which is highly expressed in mouse colonic epithelial cells, results in reduced IL-18 levels and a dysbiotic microbiota characterized by expanded representation of the bacterial phyla Bacteroidetes (Prevotellaceae) and TM7 [87]
Summary
The human microbiome, often referred to as the ‘second genome’, encompasses up to 100-fold more genes than the host genome. The microbiome as a regulator of host gene expression The notion that the activity of commensal microorganisms may influence genomic organization and gene regulation of the mammalian host gained momentum about a decade ago, when studies of intestinal tissue using DNA microarrays found major changes in gene expression between germ-free mice and mice colonized with members of the commensal microbiota [19, 20].
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