NDLI: Bugs & us: The role of the gut in autoimmunity

Content Provider	PubMed Central
Author	Luckey, David Gomez, Andres Murray, Joseph White, Bryan Taneja, Veena
Copyright Year	2013
Abstract	Rheumatoid arthritis (RA) is a multifactorial disease and requires interaction between genetic and environmental factors for predisposition. The presence of bacterial DNA of the gut residing commensals in synovium as well as dysbiosis of certain commensal bacteria in faecal samples of RA patients as compared to controls suggest a significant role of the gut flora in pathogenesis of RA. The gut commensals are involved in host immune development and function suggesting they might be critical epigenetic factors modifying autoimmune diseases like RA. This raises the question if gut-derived commensal can be exploited to generate a biomarker profile along with genetic factors to define individuals at risk. Genomic wide association studies have confirmed the HLA (human leukocyte antigen) class II genes as the strongest risk factor for predisposition to RA. HLA-DQ8 and DRB10401 molecules predispose to develop arthritis while DRB10402 provides protection. Interaction between host genetic factors like major histocompatibility complex (MHC) and gut microbiota and its impact on the development of RA is difficult to study in humans due to high variability in the genetic factors and diet. Animal models provide a means to study the molecular basis of pathogenesis thereby providing a basis for developing therapeutic strategies. Using transgenic mice expressing RA-associated and resistant HLA genes, we have developed a collagen-induced arthritis (CIA) model that shares similarities with human disease in sex-bias, autoantibody profile and phenotype. Studies in transgenic mice suggest that arthritis-susceptibility may be associated with dysbiosis in the gut microbiome. Studies in animal models underscore the impact of the gut flora in extra-intestinal diseases. Exploring the role of gut microbes will significantly advance our understanding of RA pathogenesis and may further help develop strategies for mucosal modulation of RA.
Starting Page	732
File Format	PDF
ISSN	09759174
e-ISSN	09759174
Journal	The Indian Journal of Medical Research
Issue Number	5
Volume Number	138
Language	English
Publisher	Medknow Publications & Media Pvt Ltd
Publisher Date	2013-11-01
Access Restriction	Open
Rights Holder	Medknow Publications & Media Pvt Ltd
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry, Genetics and Molecular Biology

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