Authors: Amy D. Proal PhD, Paul J. Albert, and Trevor G Marshall PhD
Publication: Current opinion in rheumatology
Purpose of review: To demonstrate how dysbiosis of the human microbiomeThe bacterial community in the human body. Many species in the microbiota contribute to the development of chronic disease. can drive autoimmune disease.
Recent findings: Humans are superorganisms. The human body harbors an extensive microbiome, which has been shown to differ in patients with autoimmuneA condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body diagnoses. Intracellular microbes slow innate immune defenses by dysregulating the VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response. nuclear receptorIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affects transcription., allowing pathogens to accumulate in tissue and blood. Molecular mimicry between pathogen and host causes further dysfunction by interfering with human protein interactions. Autoantibodies may well be created in response to pathogens.
Summary: The catastrophic failure of human metabolism observed in autoimmune disease results from a common underlying pathogenesis - the successive accumulation of pathogens into the microbiome over time, and the ability of such pathogens to dysregulate gene transcription, translation, and human metabolic processes. Auto-immune diseases are more likely passed in families due to inheritance of a familial microbiome, rather than Mendelian inheritance of genetic abnormalities. We can stimulate innate immune defenses and allow patients to target pathogens, but cell death results in immuno-pathology.