Ecem Kilic

Background: Osteoarthritis (OA) is a degenerative joint disease affecting approximately 300 million individuals globally,¹ with its prevalence increasing 113% since 1990². Pathological changes encompass cartilage and bone degradation, osteophyte formation, and synovial membrane inflammation. While biomechanical factors are well-known contributors, there is a growing recognition of systemic influences, particularly, inflammatory and immune responses linked to changes in the gastrointestinal microbiome termed the “gut-joint” axis. Understanding these systemic contributions remains an essential focus in OA research. The cellular and molecular pathogenesis is not well understood as it is a highly complex disease with many intertwined factors.

Methods: A PubMed search was performed using key terms such as “osteoarthritis”, and “gut-joint axis” and filtered results to exclude studies published more than five years prior to this review.

Results: One case-control study indicates that dysbiosis of the gut microbiome is a risk factor for osteoarthritis in older female adults. The gut microbiota in OA patients differs significantly from controls, showing reduced richness and diversity at genus and species levels. Specifically, OA patients exhibit increases in Firmicutes phylum and specific genera while Bifidobacterium longum and Faecalibacterium prausnitzii species are lower, indicating an altered gut microbiota composition³. Another study found a significant correlation between higher knee pain and increased knee effusion, with greater Streptococcus abundance associated with higher effusion, suggesting a potential causal relationship between Streptococcus and knee pain through local priming of macrophages in the synovial lining resulting in inflammation⁴. Additionally, studies have found that independent of gut microbiome, OA cases had increased levels of plasma serum lipopolysaccharide⁵. This suggests the possibility of increased intestinal mucosal permeability, or “leaky gut” as a potential contributing factor. If we accept this hypothesis, that dysbiosis of the gut microbiome has effects on distal joints, then we can potentially intervene with oral supplementation to reverse the obesity related effects on OA. Recently, oligofructose supplementation has been shown to reverse obesity’s negative effects on the gut microbiome by rescuing the altered microbial diversity and ameliorating the upregulated inflamed macrophage signature in the intestines⁶.

Conclusion: The interaction of gut microbiota, inflammation, and OA presents a promising path for therapy. Research on the gut-joint axis unveils bacterial species and functional modules linked to OA, guiding diagnostic biomarker and therapy development. Understanding this link enables personalized OA management through precision medicine approaches. By targeting gut dysbiosis and inflammation, future treatments may alleviate symptoms and modify disease progression, providing hope for OA patients.

Works Cited:

1. Abramoff B, Caldera FE. Osteoarthritis: Pathology, Diagnosis, and Treatment Options. Med Clin North Am. 2020;104(2):293-311. doi:10.1016/j.mcna.2019.10.007
2. Sophocleous A. The Role of Nutrition in Osteoarthritis Development. Nutrients. 2023;15(20):4336. Published 2023 Oct 12. doi:10.3390/nu15204336
3. Chen J, Wang A, Wang Q. Dysbiosis of the gut microbiome is a risk factor for osteoarthritis in older female adults: a case control study. BMC Bioinformatics. 2021;22(1):299. Published 2021 Jun 3. doi:10.1186/s12859-021-04199-0
4. Boer, C.G., Radjabzadeh, D., Medina-Gomez, C. et al. Intestinal microbiome composition and its relation to joint pain and inflammation. Nat Commun 10, 4881 (2019). https://doi.org/10.1038/s41467-019-12873-4
5. Loeser RF, Arbeeva L, Kelley K, et al. Association of Increased Serum Lipopolysaccharide, But Not Microbial Dysbiosis, With Obesity-Related Osteoarthritis. Arthritis Rheumatol. 2022;74(2):227-236. doi:10.1002/art.41955
6. Schott EM, Farnsworth CW, Grier A, et al. Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight. 2018;3(8):e95997. Published 2018 Apr 19. doi:10.1172/jci.insight.95997