The role of the gut and microbes in the pathogenesis of spondyloarthritis

Abstract

The intestinal microbiota is firmly implicated not only in the pathogenesis of inflammatory bowel disease (IBD) but increasingly also in the development of inflammation at extraintestinal tissue sites. Significant clinical, genetic, immunological, and microbiological overlap exists between IBD and spondyloarthritis (SpA), which indicates that pathophysiological mechanisms are shared between these diseases and may center on the intestinal microbiota. Recently, culture-independent techniques have enabled the microbiota in health and disease to be described in increasing detail. Moreover, functional studies have identified myriad host effector and regulatory pathways that shape or are shaped by this microbial community. We consider the complex relationship between SpA pathogenesis and gut microbes, with a discussion of how manipulation of the gut microbiota itself may be a promising future target for SpA therapy.

Keywords: Ankylosing spondylitis; Dysbiosis; Inflammatory bowel disease; Microbiota; Reactive arthritis; Spondyloarthritis.

Fig. 1

Multiple pathways implicated in IBD and SpA pathogenesis impact the hostemicrobiota relationship. The gut microbiota is shaped by both external factors (e.g., environmental factors or infection) and by the host itself. Barrier function, bacterial handling/homeostatic pathways (such as autophagy or ER stress), and host immune responses may contribute to the composition of the microbiota, but are also shaped by the microbiota itself (black arrows). The immune dialog between the host and the microbiota is particularly complex, as effector and regulatory responses must coexist to allow robust immunity to enteric pathogens while avoiding chronic inflammatory responses to commensal microbes (see main text). Black lines denote that these various pathways are interconnected. For instance, manipulation of diet could indirectly modulate the microbiota through direct effects on barrier function or host immunity. AMPs – antimicrobial peptides, Tconv – conventional T cell, Treg – regulatory T cell, IEL – intraepithelial lymphocytes, ILC – innate lymphoid cell, iNKT – invariant natural killer T cell, and DCs – dendritic cells.

Fig. 2

Evidence that links microbiota-associated pathways with spondyloarthropathy. Mechanisms that link the microbiota with SpA pathogenesis remain to be elucidated. Nonetheless, several lines of evidence implicate pathways that relate to the microbiota (Fig. 1) in SpA pathogenesis.