The Gut Microbiome and Rheumatoid Arthritis: A Hidden Driver of Autoimmunity and an Emerging Therapeutic Target


Authors : Dibyendu Raj

Volume/Issue : Volume 11 - 2026, Issue 1 - January


Google Scholar : https://tinyurl.com/b38uu96d

Scribd : https://tinyurl.com/3jxe77t4

DOI : https://doi.org/10.38124/ijisrt/26jan387

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.


Abstract : Rheumatoid arthritis (RA) is a chronic, systemic, immune-mediated inflammatory disease characterized by persistent synovitis, progressive joint destruction, functional disability, and a wide spectrum of extra-articular manifestations. Despite substantial advances in disease-modifying therapies, RA continues to impose a significant global health burden, with rising prevalence and substantial socioeconomic costs. In recent years, growing attention has been directed toward the gut–immune axis, revealing the gut microbiota as a central regulator of immune homeostasis and a potential driver of autoimmune diseases, including RA. Accumulating evidence from animal models, human cohort studies, and translational research indicates that alterations in gut microbial composition and function—collectively referred to as dysbiosis—may precede clinical disease onset, influence immune tolerance, and modulate disease severity and therapeutic response. This comprehensive review integrates current knowledge on the epidemiology, etiology, immunopathogenesis, and systemic manifestations of RA, with a particular emphasis on the mechanistic and translational role of the gut microbiome. We discuss microbial–host interactions, immune pathways, emerging microbiome-derived biomarkers, and evolving microbiota-targeted therapeutic strategies, highlighting their potential to reshape the future of personalized RA management.

Keywords : Rheumatoid Arthritis, Gut Microbiome, Pro-Inflammatory Immune Responses, Autoimmunity, Gut-Joint Connection, Microbiome Science.

References :

  1. GBD 2021 Rheumatoid Arthritis Collaborators. Global, regional, and national burden of rheumatoid arthritis, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023 Sep 25;5(10):e594-e610. doi: 10.1016/S2665-9913(23)00211-4. PMID: 37795020; PMCID: PMC10546867.
  2. Ma Y, Chen H, Lv W, Wei S, Zou Y, Li R, Wang J, She W, Yuan L, Tao J, Guo X, Bi S, Tian H, Ma Y, Sun H, Sun C, Xu J, Dong Y, Kang J, Lv H, Zhang M, Jiang Y. Global, regional and national burden of rheumatoid arthritis from 1990 to 2021, with projections of incidence to 2050: a systematic and comprehensive analysis of the Global Burden of Disease study 2021. Biomark Res. 2025 Mar 24;13(1):47. doi: 10.1186/s40364-025- 00760-8. PMID: 40128880; PMCID: PMC11931880.
  3. Bakinowska E, Stańska W, Kiełbowski K, Szwedkowicz A, Boboryko D, Pawlik A. Gut Dysbiosis and Dietary Interventions in Rheumatoid Arthritis-A Narrative Review. Nutrients. 2024 Sep 23;16(18):3215. doi: 10.3390/nu16183215. PMID: 39339815; PMCID: PMC11435214.
  4. Wang DW, Pang XT, Zhang H, Gao HX, Leng YF, Chen FQ, Zhang R, Feng Y, Sun ZL. Gut microbial dysbiosis in rheumatoid arthritis: a systematic review protocol of case- control studies. BMJ Open. 2022 Apr 1;12(4): e052021. doi: 10.1136/bmjopen-2021- 052021. PMID: 35365513; PMCID: PMC8977794.
  5. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013 Nov 5;2: e01202. doi: 10.7554/eLife.01202. PMID: 24192039; PMCID: PMC3816614.
  6. Pianta A, Arvikar S, Strle K, Drouin EE, Wang Q, Costello CE, Steere AC. Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients with Rheumatoid Arthritis. Arthritis Rheumatol. 2017 May;69(5):964-975. doi: 10.1002/art.40003. Epub 2017 Apr 7. PMID: 27863183; PMCID: PMC5406252.
  7. Maeda Y, Takeda K. Host-microbiota interactions in rheumatoid arthritis. Exp Mol Med. 2019 Dec 11;51(12):1-6. doi: 10.1038/s12276-019-0283-6. PMID: 31827063; PMCID: PMC6906371.
  8. Su QY, Zhang Y, Qiao D, Song X, Shi Y, Li RQ, et al. Gut microbiota dysbiosis in rheumatoid arthritis: a systematic review and meta-analysis. Explor Med. 2024; 5:709–19.
  9. Kurkó J, Besenyei T, Laki J, Glant TT, Mikecz K, Szekanecz Z. Genetics of rheumatoid arthritis - a comprehensive review. Clin Rev Allergy Immunol. 2013 Oct;45(2):170-9. doi: 10.1007/s12016-012-8346-7. PMID: 23288628; PMCID: PMC3655138.
  10. Karami J, Aslani S, Jamshidi A, Garshasbi M, Mahmoudi M. Genetic implications in the pathogenesis of rheumatoid arthritis; an updated review. Gene. 2019 Jun 20; 702:8-16. doi: 10.1016/j.gene.2019.03.033. Epub 2019 Mar 20. PMID: 30904715.
  11. Terao C, Raychaudhuri S, Gregersen PK. Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis. Annu Rev Genomics Hum Genet. 2016 Aug 31; 17:273-301. doi: 10.1146/annurev-genom-090314-045919. Epub 2016 May 23. PMID: 27216775; PMCID: PMC6727201.
  12. Kurkó J, Besenyei T, Laki J, Glant TT, Mikecz K, Szekanecz Z. Genetics of rheumatoid arthritis - a comprehensive review. Clin Rev Allergy Immunol. 2013 Oct;45(2):170-9. doi: 10.1007/s12016-012-8346-7. PMID: 23288628; PMCID: PMC3655138.
  13. Berthelot JM, Darrieutort-Laffite C, Le Goff B. Contribution of HLA DRB1, PTPN22, and CTLA4, to RA dysbiosis. Joint Bone Spine. 2022; 89(6):105446. doi: 10.1016/j.jbspin.2022.105446. Epub 2022 Aug 6. PMID: 35940545.
  14. Frisell T, Holmqvist M, Källberg H, Klareskog L, Alfredsson L, Askling J. Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 2013; 65(11):2773-82. doi: 10.1002/art.38097. PMID: 23897126.
  15. Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis
  16. D. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 2010; 32(6):815-27. doi: 10.1016/j.immuni.2010.06.001. PMID: 20620945; PMCID: PMC2904693.
  17. Flannigan KL, Denning TL. Segmented filamentous bacteria-induced immune responses: a balancing act between host protection and autoimmunity. Immunology. 2018; 154(4):537–46. doi: 10.1111/imm.12950. Epub ahead of print. PMID: 29771448; PMCID: PMC6050222.
  18. Maeda, Y., Takeda, K. Host–microbiota interactions in rheumatoid arthritis. Exp Mol Med 51, 1–6 (2019). https://doi.org/10.1038/s12276-019-0283-6
  19. Vivienne Woo, Emily M. Eshleman, Seika Hashimoto-Hill, Jordan Whitt, Shu-en Wu, Laura Engleman, Taylor Rice, Rebekah Karns, Joseph E. Qualls, David B. Haslam, Bruce Vallance, Theresa Alenghat,
  20. Vaahtovuo J, Munukka E, Korkeamäki M, Luukkainen R, Toivanen P. Fecal microbiota in early rheumatoid arthritis. J Rheumatol. 2008 Aug;35(8):1500-5. Epub 2008. PMID: 18528968.
  21. Zhao T, Wei Y, Zhu Y, Xie Z, Hai Q, Li Z, Qin D. Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities. Front Immunol.; 13:1007165. doi: 10.3389/fimmu.2022.1007165. PMID: 36159786; PMCID: PMC9499173.
  22. Maeda, Y., Takeda, K. Host–microbiota interactions in rheumatoid arthritis. Exp Mol Med 51, 1–6 (2019). https://doi.org/10.1038/s12276-019-0283-6
  23. Zhang, X., et al. (2015). The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nature Medicine, 21(8), 895–905. https://doi.org/10.1038/nm.3914
  24. Liu, X., et al. (2016). Role of the gut microbiome in modulating arthritis progression in mice. Scientific Reports, 6, 30594. https://doi.org/10.1038/srep30594
  25. Zhao T, Wei Y, Zhu Y, Xie Z, Hai Q, Li Z, Qin D. Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities. Front Immunol. 2022; 13:1007165. doi: 10.3389/fimmu.2022.1007165. PMID: 36159786; PMCID: PMC9499173.
  26. Maeda Y, Takeda K. Host-microbiota interactions in rheumatoid arthritis. Exp Mol Med. 2019; 51(12):1-6. doi: 10.1038/s12276-019-0283-6. PMID: 31827063; PMCID: PMC6906371.
  27. Chen, B., et al. (2021). The key role of gut microbiota in the pathogenesis and treatment of rheumatoid arthritis. Frontiers in Pharmacology, 12, 626396. https://doi.org/10.3389/fphar.2021.626396
  28. Smolen, J. S., et al. (2018). Rheumatoid arthritis. Nature Reviews Disease Primers, 4(1), 18001. https://doi.org/10.1038/s41572-018-0050-3.
  29. O’Dwyer, D. N., & Long, J. (2019). Rheumatoid arthritis-associated interstitial lung disease: prevalence, pathogenesis and outcomes. The Journal of Rheumatology, 46(4), 360–367
  30. Smolen, J. S., Aletaha, D., Barton, A., et al. (2018). Rheumatoid arthritis. Nature Reviews Disease Primers, 4, 18001. doi:10.1038/s41572-018-0050-3
  31. Patel R, Killeen RB, Akhondi H. Felty Syndrome. In: StatPearls. Treasure Island (FL): StatPearls
  32. Reddy AK, Kolfenbach JR, Palestine AG. Ocular manifestations of rheumatoid arthritis. Curr Opin Ophthalmol. 2022 Nov 1;33(6):551-556. doi: 10.1097/ICU.0000000000000890. Epub 2022. PMID: 36165413.
  33. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin North Am. 2007; 33(4):835-54, vii. doi: 10.1016/j.rdc.2007.08.002. PMID: 18037120; PMCID: PMC2212596.
  34. Fraenkel, L., Bathon, J. M., England, B. R., St. Clair, E. W., Arayssi, T., Carandang, K., Deane, K. D., … Sparks, J. A. (2021). 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care & Research, 73(7), 924–939. https://doi.org/10.1002/acr.24596
  35. Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012). The impact of the gut microbiota on human health: an integrative view. Cell, 148(6), 1258–1270. https://doi.org/10.1016/j.cell.2012.01.035
  36. Wallace, T. C., & Miles, E. A. (2014). Omega-3 polyunsaturated fatty acids and their role in immune function, nutrition, and health. American Journal of Clinical Nutrition, 100(1), 348S–354S. https://doi.org/10.3945/ajcn.114.083978
  37. Zhu, C., Song, H., Chen, Q., Liu, Z., & Wu, S. (2018). Methotrexate alters gut microbiota in rheumatoid arthritis patients. Clinical Rheumatology, 37(1), 123–130. https://doi.org/10.1007/s10067-017-3805-2
  38. Mai, V., & Greenwald, B. (2007). Sulfasalazine and the gut microbiota in RA.
  39. Inflammopharmacology, 15(5), 157–162. https://doi.org/10.1007/s10787-007-0004-3
  40. Johnson, E. E., & Smith, R. D. (2019). Hydroxychloroquine and gut microbiome modulation. Journal of Antimicrobial Chemotherapy, 74(12), 3473–3480. https://doi.org/10.1093/jac/dkz348
  41. Zhang, X., Zhang, D., Jia, H., Feng, Q., Wang, D., Liang, D.,  & Li, J. (2015). Nature Medicine, 21(8), 895–905. https://doi.org/10.1038/nm.3914
  42. Schnitzer, T., et al. (2016). Impact of NSAIDs on intestinal microbiota: protective roles of probiotics. Gastroenterology, 150(2), S639. https://doi.org/10.1053/j.gastro.2015.12.723
  43. Huang, R., Ning, Z., Yang, F., & Wang, W. (2020). Effects of Bifidobacterium, Lactobacillus, and Faecalibacterium prausnitzii in inflammation models. Frontiers in Immunology, 11, 619356. https://doi.org/10.3389/fimmu.2020.619356
  44. Manfredo Vieira, S., Hiltensperger, M., Kumar, V., Zegarra-Ruiz, D., Dehner, C., Khan, N. & Kriegel, M.  A. (2018).  Science, 359(6380), 1156–1161. https://doi.org/10.1126/science.aar7201
  45. Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SMH, Zakeri A, Alagheband Bahrami A, Brockmueller A, Shakibaei M. Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies. Cells. 2021; 10(11):3017. doi: 10.3390/cells10113017. PMID: 34831240; PMCID: PMC8616543.
  46. Shan L, Chelliah R, Rahman SME, Hwan Oh D. Unraveling the gut microbiota's role in Rheumatoid arthritis: dietary pathways to modulation and therapeutic potential. Crit Rev Food Sci Nutr. 2025; 65(17):3291-3301. doi: 10.1080/10408398.2024.2362412. 2024. PMID: 38832654.

Rheumatoid arthritis (RA) is a chronic, systemic, immune-mediated inflammatory disease characterized by persistent synovitis, progressive joint destruction, functional disability, and a wide spectrum of extra-articular manifestations. Despite substantial advances in disease-modifying therapies, RA continues to impose a significant global health burden, with rising prevalence and substantial socioeconomic costs. In recent years, growing attention has been directed toward the gut–immune axis, revealing the gut microbiota as a central regulator of immune homeostasis and a potential driver of autoimmune diseases, including RA. Accumulating evidence from animal models, human cohort studies, and translational research indicates that alterations in gut microbial composition and function—collectively referred to as dysbiosis—may precede clinical disease onset, influence immune tolerance, and modulate disease severity and therapeutic response. This comprehensive review integrates current knowledge on the epidemiology, etiology, immunopathogenesis, and systemic manifestations of RA, with a particular emphasis on the mechanistic and translational role of the gut microbiome. We discuss microbial–host interactions, immune pathways, emerging microbiome-derived biomarkers, and evolving microbiota-targeted therapeutic strategies, highlighting their potential to reshape the future of personalized RA management.

Keywords : Rheumatoid Arthritis, Gut Microbiome, Pro-Inflammatory Immune Responses, Autoimmunity, Gut-Joint Connection, Microbiome Science.

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