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The gut-joint axis in spondyloarthritis: immunological, microbial, and clinical insights

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Abstract

The strong genetic and clinical overlaps between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) have placed much needed focus on the gut-joint axis of inflammation in SpA, leading to three key hypotheses that attempt to unravel this complex relationship. The arthritogenic peptide hypothesis and the aberrant cellular trafficking hypothesis have been put forth to rationalize the manner by which the innate and adaptive immune systems cooperate and converge during SpA pathogenesis. The bacterial dysbiosis hypothesis discusses how changes in the microbiome lead to architectural and immunological consequences in SpA. These theories are not mutually exclusive, but can provide an explanation as to why subclinical gut inflammation may sometimes precede joint inflammation in SpA patients, thereby implying a causal relationship. Such investigations will be important in informing therapeutic decisions which may be common to both SpA and IBD. However, these hypotheses can also offer insights for a coincident inflammatory relationship between the gut and the joint, particularly when assessing the immunological players involved. Insights from understanding how these systems might affect the gut and joint differently will be equally imperative to address where the therapeutic differences lie between the two diseases. Collectively, this knowledge has practical implications in predicting the likelihood of IBD development in SpA or presence of coincident SpA-IBD, uncovering novel therapeutic targets, and redesigning currently approved treatments. It is evident that a multidisciplinary approach between the rheumatology and gastroenterology fields cannot be ignored, when it comes to the care of SpA patients at risk of IBD or vice versa.

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Grant support: Canadian Institutes of Health Research

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Authors and Affiliations

  1. Schroeder Arthritis Institute, University Health Network, 60 Leonard Avenue, 5, Toronto, Ontario, KD-408, Canada

    Zoya Qaiyum, Melissa Lim & Robert D. Inman

  2. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    Robert D. Inman

  3. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Robert D. Inman

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Qaiyum, Z., Lim, M. & Inman, R.D. The gut-joint axis in spondyloarthritis: immunological, microbial, and clinical insights. Semin Immunopathol 43, 173–192 (2021). https://doi.org/10.1007/s00281-021-00845-0

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