The Role of the Microbiome in Rheumatic Diseases

Abstract

There is a growing understanding of the mechanisms by which the influence of the microbiota projects beyond sites of primary mucosal occupation to other human body systems. Bacteria present in the intestinal tract exert a profound effect on the host immune system, both locally and at distant sites. The oral cavity has its own characteristic microbiota, which concentrates in periodontal tissues and is in close association with a permeable epithelium. In this review we examine evidence which supports a role for the microbiome in the aetiology of rheumatic disease. We also discuss how changes in the composition of the microbiota, particularly within the gastrointestinal tract, may be affected by genetics, diet, and use of antimicrobial agents. Evidence is presented to support the theory that an altered microbiota is a factor in the initiation and perpetuation of inflammatory diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA), and inflammatory bowel disease (IBD). Mechanisms through which the microbiota may be involved in the pathogenesis of these diseases include altered epithelial and mucosal permeability, loss of immune tolerance to components of the indigenous microbiota, and trafficking of both activated immune cells and antigenic material to the joints. The potential to manipulate the microbiome, by application of probiotics and faecal microbial transplant (FMT), is now being investigated. Both approaches are in their infancy with regard to management of rheumatic disease but their potential is worthy of consideration, given the need for novel therapeutic approaches, and the emerging recognition of the importance of microbial interactions with human hosts.

Identifying strains that contribute to complex diseases through the study of microbial inheritance

“…Thus, the dynamics of their exchange (inheritance) would be more complex than in the simplified example presented above and, in the case of twins, help define the degree of concordance or discordance for disease. Crohn's disease, rheumatoid arthritis, and multiple sclerosis are examples of complex diseases where microbial agents have been hypothesized to have etiologic roles (30)(31)(32)(33)(34)(35)(36). Concordance for disease in monozygotic twins is below 40% in all three diseases (37)(38)(39).…”

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

“…[1][2][3][4][5] Dysbiosis may refer to disturbances in the microbial community composition, but can also refer to disturbed interaction between the microbiota and the host. Disturbance of the microbial community due to for example antibiotic use can lead to outgrowth of socalled pathobionts.…”

Dynamics of Gut Microbiota in Autoimmune Lupus

“…Increasing evidence in recent years suggests that the host microbiota and immune system interact to maintain tissue homeostasis in healthy individuals (2)(3)(4)(5)(6). The importance of microbiota for the host is highlighted by altered immune responses in the absence of commensal bacteria, where both systemic and gut-specific lymphoid tissues are generally smaller and less developed (7).…”