Autoimmune disease in the era of the metagenome.
Studies of autoimmune disease have focused on the characteristics of the identifiable antibodies. But as our knowledge of the genes associated with the disease states expands, we understand that humans must be viewed as superorganisms in which a plethora of bacterial genomes - a metagenome - work in tandem with our own. The NIH has estimated that 90% of the cells in Homo sapiens are microbial and not human in origin. Some of these microbes create metabolites that interfere with the expression of genes associated with autoimmune disease. Thus, we must re-examine how human gene transcription is affected by the plethora of microbial metabolites. We can no longer assume that antibodies generated in autoimmune disease are created solely as autoantibodies to human DNA. Evidence is now emerging that the human microbiota accumulates during a lifetime, and a variety of persistence mechanisms are coming to light. In one model, obstruction of VDR nuclear-receptor-transcription prevents the innate immune system from making key antimicrobials, allowing the microbes to persist. Genes from these microbes must necessarily impact disease progression. Recent efforts to decrease this VDR-perverting microbiota in patients with autoimmune disease have resulted in reversal of autoimmune processes. As the NIH Human Microbiome Project continues to better characterize the human metagenome, new insights into autoimmune pathogenesis are beginning to emerge.
Proal
Amy D
AD
Georgetown University, USA. amy.proal@gmail.com
Albert
Paul J
PJ
Marshall
Trevor
T
D017738:Alkanesulfonic Acids / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D023281:Genomics; D006801:Humans; D007113:Immunity, Innate; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics; D054892:Metagenome / Q000235:genetics*
D017738:Alkanesulfonic Acids; D001323:Autoantibodies; D004269:DNA, Bacterial; C027502:capnine