Osteoarthritis Can Also Start in the Gut: The Gut-Joint Axis

Osteoarthritis is a common cause of pain and disability with an increasing prevalence among the global population (Hunter and Bierma-Zeinstra in Lancet 393(10182):1745-1759, 2019; Zhang and Jordan in Clinics in Geriatric Medicine 26(3):355-369, 2010). Altered immune responses and low-grade systemic inflammation driven by gut dysbiosis are being increasingly recognized as contributing factors to the pathophysiology of OA (Tan et al. in International Journal of Rheumatic Diseases. https://doi.org/10.1111/1756-185X.14123, 2021; Binvignat et al. in Joint, Bone, Spine 88(5):105203, 2021; Ramasamy et al. in Nutrients 13(4):1272, 2021), which increased the interest in the so-called "gut-joint axis". The various microbiota in the gastrointestinal tract is commonly referred to as the gut microbiome. The gut microbiome is affected by age, sex, and immune system activity as well as medications, environment, and diet (Arumugam in Nature. https://doi.org/10.1038/nature09944, 2011). The microbiome is pivotal to maintain host health and contributes to nutrition, host defense, and immune development (Nishida et al. in Clinical Journal of Gastroenterology 11:1-10, 2018). Alterations in this microbiome can induce dysbiosis, which is associated with many human disease states including allergies, autoimmune disease, diabetes, and cancer (Lin and Zhang in BMC Immunology 18(1):2, 2017). A gut-joint axis is proposed as a link involving the gastrointestinal microbiome, the immune response that it induces, and joint health.

Emerging evidence has shown that there are specific changes in the microbiome that are associated with osteoarthritis, including increased Firmicutes/Bacteroides ratio, Streptococcus spp. prevalence, and local inflammation (Collins in Osteoarthritis and Cartilage. https://doi.org/10.1016/j.joca.2015.03.014, 2015; Rios in Science and Reports. https://doi.org/10.1038/s41598-019-40601-x, 2019; Schott in JCI insight. https://doi.org/10.1172/jci.insight.95997, 2018; Boer et al. in Nature Communications 10:4881, 2019). Both the innate and adaptive immune systems are affected by the gut microbiome and can become dysregulated in dysbiosis which ultimately triggers events associated with joint OA.

The gut is an intriguing and novel target for OA therapy. Dietary modification or supplementation with fiber, probiotics, or prebiotics could provide a positive impact on the gut joint axis.