Fig. 7

The model of the interplay between the human innate and adaptive genome in health and disease transformation. The human innate and adaptive genomes form a holistic functional phenotype but are also in constant competition. The regulation of the nervous, immune, metabolic, and commensal microbiota constitutes the four major features and regulatory forces of human health and disease states. These forces interact with each other, and microbial dysbiosis can lead to the disruption of other forces and vice versa. The innate genome requires (a) the necessary exposure to commensal microbiota and a controllable microbial community, (b) an intact microbial barrier, (c) the ability to resist damage from microbial genetic mutations, and (d) the ability to utilize beneficial products of the adaptive genome and metabolize harmful ones to maintain a healthy steady state (with the innate genome in the dominant position). Conversely, (e) inadequate exposure to appropriate microbiota (which can lead to germ-free syndrome in extreme cases) or microbial overgrowth, (f) microbes or their components (e.g. LPS) entering the circulation through an incomplete barrier and causing harm to other tissues and organs, (g) microbial genetic mutations causing additional damage, and (h) a decrease in beneficial microbial products and an increase in harmful ones can lead humans towards disease progression (with the adaptive genome dominant). LPS Lipopolysaccharides, TMA Trimethylamine, TMAO Trimethylamine N-oxide, PAGln Phenylacetylglutamine, ClpB a melanocyte-stimulating hormone (α-MSH) analogue, BCAAs Branched-chain amino acids, SCFAs Short-chain fatty acids, RKH Arginyl-lysyl-histidine