The microbiome and rheumatoid arthritis

Abstract

Humans are not (and have never been) alone. From the moment we are born, millions of micro-organisms populate our bodies and coexist with us rather peacefully for the rest of our lives. This microbiome represents the totality of micro-organisms (and their genomes) that we necessarily acquire from the environment. Micro-organisms living in or on us have evolved to extract the energy they require to survive, and in exchange they support the physiological, metabolic and immune capacities that have contributed to our evolutionary success. Although currently categorized as an autoimmune disorder and regarded as a complex genetic disease, the ultimate cause of rheumatoid arthritis (RA) remains elusive. It seems that interplay between predisposing genetic factors and environmental triggers is required for disease manifestation. New insights from DNA sequence-based analyses of gut microbial communities and a renewed interest in mucosal immunology suggest that the microbiome represents an important environmental factor that can influence autoimmune disease manifestation. This Review summarizes the historical clues that suggest a possible role for the microbiota in the pathogenesis of RA, and will focus on new technologies that might provide scientific evidence to support this hypothesis.

Key Points

  • In rheumatoid arthritis (RA)—a complex, polygenic, autoimmune disorder with a major impact on individuals and society—genes have a role, but environmental factors are required for disease manifestation

  • Multiple lines of epidemiological and clinical investigation have implicated several micro-organisms in RA pathogenesis; however, causation could not be established

  • The microbiome is defined as the totality of micro-organisms and their genes inhabiting a unique environment; the human microbiome outnumbers human genes by several orders of magnitude

  • Understanding of the role of micro-organisms in modulating health and disease has been greatly advanced by culture-independent DNA sequencing technologies and novel insights into mucosal immunology

  • Germ-free and gnotobiotic experiments have provided a deeper understanding of host–microbial interactions and have shown that gut bacteria can induce autoimmunity in genetically predisposed animal models

  • Studies are underway to assess the role of the microbiome in human RA and related diseases in the hope that disease mechanisms will be elucidated and therapeutic targets identified

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Figure 1: Historical, literary, artistic and paleopathological evidence of RA as a New World disease that has 'spread' to the rest of the world.
Figure 2: Culture-independent genomic analysis of the human microbiome.
Figure 3: Host–microbiota interactions in health and inflammatory arthritis.
Figure 4: Multiple animal models of inflammatory arthritis have demonstrated that the gut microbiota is critical for the development of disease.

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Acknowledgements

The writing of this manuscript has been supported in part by Grant No. RC2 AR05898 to S. B. Abramson from the US NIH through the American Recovery and Reinvestment Act (ARRA) of 2009, and by KL2 Program in Translational Research to J. U. Scher, Grant No. 1 UL1 RR029893 from the National Center for Research Resources, NIH. The authors thank Ms. Ann Rupel for assistance in preparation of the manuscript.

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J. U. Scher and S. B. Abramson contributed equally to all aspects of the preparation of this manuscript.

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Scher, J., Abramson, S. The microbiome and rheumatoid arthritis. Nat Rev Rheumatol 7, 569–578 (2011). https://doi.org/10.1038/nrrheum.2011.121

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