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The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions

Key Points

  • Emerging data implicate the human microbiome in the pathogenesis of inflammatory arthritides

  • Mucosal sites exposed to high load of bacterial antigens (i.e. gut) may represent the initial site of tolerance break in rheumatoid arthritis, psoriatic arthritis and related diseases

  • Microbial and dietary metabolites (e.g. SCFAs and MCFAs) have immunomodulatory properties that could be exploited for the treatment of rheumatic disorders

  • Pharmacomicrobiomics is a novel field of research that investigates the effect of variations within the human microbiome on drugs and could facilitate precision medicine in cancer and autoimmunity

Abstract

The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host–microorganism interaction is likely to go well beyond taxonomic, correlative observations. In fact, most advances in the field relate to the functional and metabolic capabilities of these microorganisms and their influence on mucosal immunity and systemic inflammation. An intricate relationship between the microbiome and the diet of the host is now fully recognized, with the microbiota having an important role in the degradation of polysaccharides into active metabolites. This Review summarizes the current knowledge on the metabolic role of the microbiota in health and rheumatic disease, including the advances in pharmacomicrobiomics and its potential use in diagnostics, therapeutics and personalized medicine.

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Figure 1: Immune and disease-modulating capabilities of intestinal microbial metabolites and probiotics.

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Acknowledgements

S.A.-R. is supported by the Arthritis National Research Foundation (grant 15-A0-00-004310-01), the Netherlands Organization for Scientific Research (VENI grant 916.12.039) and the Dutch Arthritis Foundation (AFS 14-1-291 grant). S.B.A. is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) through the American Recovery and Reinvestment Act of 2009 (grant RC2 AR058986) and by The Colton Center for Autoimmunity. J.U.S. is supported by NIAMS (grant K23AR064318), the Arthritis Foundation (Innovative Research Grant), The Colton Center for Autoimmunity; and The Riley Family Foundation.

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Abdollahi-Roodsaz, S., Abramson, S. & Scher, J. The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions. Nat Rev Rheumatol 12, 446–455 (2016). https://doi.org/10.1038/nrrheum.2016.68

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