THE GUT-HEART-JOINT AXIS: MICROBIOME-MEDIATED MECHANISMS IN RHEUMATOID ARTHRITIS AND CARDIOVASCULAR DISEASE
Main Article Content
Keywords
gut-heart-joint axis, rheumatoid arthritis, cardiovascular disease, gut microbiota, immunological crosstalk.
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily affecting joints, but its impact extends beyond the synovium. Notably, RA confers a 1.5–2-fold higher risk of cardiovascular disease (CVD), including accelerated atherosclerosis. Emerging evidence implicates the gut microbiome as a pivotal mediator in this triad, forming a “gut-heart-joint axis.” This review synthesizes current knowledge on how intestinal dysbiosis and microbial metabolites contribute to RA pathogenesis and heightened CVD risk. We discuss key microbiome-mediated pathways – from impaired gut barrier function and immune cell trafficking to molecular mimicry and proinflammatory metabolites – that link RA and CVD pathophysiology. We highlight diagnostic implications, such as distinct gut microbiota signatures in preclinical RA and potential microbial or metabolic biomarkers for CVD risk stratification.
A balanced overview of treatment strategies is provided, encompassing conventional RA therapies (DMARDs and biologics) that incidentally modulate the microbiome, as well as emerging interventions targeting dysbiosis (dietary fiber, probiotics, and even fecal microbiota transplantation). Throughout, we emphasize clarity for the general medical professional, reviewing immunological crosstalk (e.g. Th17 cells, cytokines) in approachable terms. The gut-heart-joint axis paradigm offers a unifying framework that not only enhances our understanding of RA’s systemic nature but also uncovers novel avenues for diagnosis and therapy aimed at improving both joint and cardiovascular outcomes. By integrating microbiome science with clinical rheumatology and cardiology, this review outlines a path toward precision medicine approaches that could mitigate inflammation and comorbidity in RA.
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9. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165(1):111–24.
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14. Ott SJ, El Mokhtari NE, Musfeldt M, Hellmig S, Freitag S, Rehman A, et al. Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease. Circulation. 2006;113(7):929–37.
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16. Lanter BB, Sauer K, Davies DG. Bacteria present in carotid arterial plaques are found as biofilm deposits which may contribute to enhanced risk of plaque rupture. mBio. 2014;5(3):e01206–14.
17. Marietta EV, Murray JA, Luckey DH, Jeraldo PR, Lamba A, Patel R, et al. Suppression of inflammatory arthritis by human gut-derived Prevotella histicola in humanized mice. Arthritis Rheumatol. 2016;68(11):2878–88.
18. Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol. 2016;68(11):2646–61.
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20. Karpouzas GA, Ormseth MJ, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by inhibiting coronary plaque inflammation. Arthritis Rheumatol. 2020;72(9):1467–75.
21. Breban M, Tap J, Leboime A, Said-Nahal R, Loubet P, Boëlle PY, et al. Faecal microbiota transplantation in refractory rheumatoid arthritis: a proof of concept study. Ann Rheum Dis. 2021;80(Suppl 1):202.
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23. Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K, et al. Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med. 2016;8(369):369ra176.
24. Potempa J, Mydel P, Koziel J. The case for periodontitis in the pathogenesis of rheumatoid arthritis. Nat Rev Rheumatol. 2017;13(10):606–20.
25. Firestein GS, McInnes IB. Immunopathogenesis of rheumatoid arthritis. Immunity. 2017;46(2):183–96.
26. Yang Y, Zhu Y, Luo Y, Li S, Zhang Y, Wang Z. Mucosal immunity and rheumatoid arthritis: an update on mechanisms and therapeutic potential. Autoimmun Rev. 2025;24(3):103775.
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Nov 18, 2025
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Subarnarekha Maitra, Sreemoy Kanti Das, Saravanakumar Parameswaran, Poulami Sen, Maitreyee Mukherjee, Dibya Sinha, Tathagata Roy, & Sabarieshwaran Kullan. (2025). THE GUT-HEART-JOINT AXIS: MICROBIOME-MEDIATED MECHANISMS IN RHEUMATOID ARTHRITIS AND CARDIOVASCULAR DISEASE. Journal of Population Therapeutics and Clinical Pharmacology, 32(10), 878-898. https://doi.org/10.53555/gpx0nj70
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Author Biographies
Subarnarekha Maitra
Faculty of Pharmacy, Lincoln University College, Selangor, Malaysia.
Sreemoy Kanti Das
Faculty of Pharmacy, Lincoln University College, Selangor, Malaysia.
Saravanakumar Parameswaran
Faculty of Pharmacy, Lincoln University College, Selangor, Malaysia.
Poulami Sen
Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata- Group of Institutions
Maitreyee Mukherjee
Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata-Group of Institutions.
Dibya Sinha
Department of Otorhinolaryngology, Regional Institute of Medical Sciences, Manipur, India
Tathagata Roy
Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata-Group of Institutions.
Sabarieshwaran Kullan
Peregrine Research Solutions, Tamil Nadu, India.
How to Cite
Subarnarekha Maitra, Sreemoy Kanti Das, Saravanakumar Parameswaran, Poulami Sen, Maitreyee Mukherjee, Dibya Sinha, Tathagata Roy, & Sabarieshwaran Kullan. (2025). THE GUT-HEART-JOINT AXIS: MICROBIOME-MEDIATED MECHANISMS IN RHEUMATOID ARTHRITIS AND CARDIOVASCULAR DISEASE. Journal of Population Therapeutics and Clinical Pharmacology, 32(10), 878-898. https://doi.org/10.53555/gpx0nj70