The microbiome and rheumatoid arthritis

The microbes that inhabit our bodies play an important part in regulating the homeostasis of the immune system—disequilibrium in this symbiotic relationship can lead to development of disease. In this Review, the authors present an overview of the historical evidence implicating microbes in the development of rheumatoid arthritis (RA), and describe how the use of DNA sequencing techniques and germ–free animal models of disease are elucidating the role of host–microbial interactions in the pathogenesis of RA. 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.