title: Microbe-microbe and host-microbe interactions drive microbiome dysbiosis and inflammatory processes.
abstract: An extensive microbiome comprised of bacteria, viruses, bacteriophages, and fungi is now understood to persist in nearly every human body site, including tissue and blood. The genomes of these microbes continually interact with the human genome in order to regulate host metabolism. Many components of this microbiome are capable of both commensal and pathogenic activity. They are additionally able to persist in both 'acute' and chronic forms. Inflammatory conditions historically studied separately (autoimmune, neurological and malignant) are now repeatedly tied to a common trend: imbalance or dysbiosis of these microbial ecosystems. Population-based studies of the microbiome can shed light on this dysbiosis. However, it is the collective activity of the microbiome that drives inflammatory processes via complex microbe-microbe and host-microbe interactions. Many microbes survive as polymicrobial entities in order to evade the immune response. Pathogens in these communities alter their gene expression in ways that promote community-wide virulence. Other microbes persist inside the cells of the immune system, where they directly interfere with host transcription, translation, and DNA repair mechanisms. The numerous proteins and metabolites expressed by these pathogens further dysregulate human gene expression in a manner that promotes imbalance and immunosuppression. Molecular mimicry, or homology between host and microbial proteins, complicates the nature of this interference. When taken together, these microbe-microbe and host-microbe interactions are capable of driving the large-scale failure of human metabolism characteristic of many different inflammatory conditions.
authors.affiliation: Autoimmunity Research Foundation, Thousand Oaks, CA 91360, USA.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Proal
authors.affiliation: 4M-klinikken, Oslo 0862, Norway.
authors.forename: Inge A
authors.initials: IA
authors.lastname: Lindseth
authors.affiliation: Autoimmunity Research Foundation, Thousand Oaks, CA 91360, USA.
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Marshall
mesh_terms: D000818:Animals; D064806:Dysbiosis / Q000276:immunology / Q000382:microbiology* / Q000821:virology; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D064307:Microbiota / Q000502:physiology*