Skip to main content

Advertisement

SpringerLink
Log in

The therapeutic effect of probiotics on rheumatoid arthritis: a systematic review and meta-analysis of randomized control trials

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis is an autoimmune disease in which probiotics appears to have an immune modulating action along with decreased inflammatory process. Therefore, we aim to investigate the efficacy of probiotics as an adjuvant therapy for rheumatoid arthritis. A comprehensive literature search was performed using nine databases including PubMed and Web of Science. Interesting data was extracted and meta-analyzed. We assessed the risk of bias using Cochrane Collaboration’s tool. The protocol was registered in PROSPERO (CRD 42016036769). We found nine studies involving 361 patients who met our eligibility criteria. Our meta-analysis indicated that pro-inflammatory cytokine IL-6 was significantly lower in the probiotics compared with the placebo group (standardized mean difference = − 0.708; 95% confidence interval (CI) − 1.370 to 0.047, P = 0.036). However, there was no difference between probiotics and placebo in disease activity score (mean difference 0.023; 95% CI − 0.584 to 0.631, P = 0.940). Probiotics lowered pro-inflammatory cytokines IL-6 in RA; however, its clinical effect is still unclear. Hence, many high-quality randomized controlled trials (RCTs) are still needed to prove this effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brooks PM (2006) The burden of musculoskeletal disease—a global perspective. Clin Rheumatol 25(6):778–781

    Article  PubMed  Google Scholar 

  2. Dieppe P (2002) Epidemiology of the rheumatic diseases second edition. AJ Silman, MC Hochberg (Eds). Oxford: Oxford University Press, 2001, pp. 377, £95.00. ISBN: 0192631497. Int J Epidemiol 31(5):1079–1080

    Article  Google Scholar 

  3. Alamanos Y, Drosos AA (2005) Epidemiology of adult rheumatoid arthritis. Autoimmun Rev 4(3):130–136

    Article  PubMed  Google Scholar 

  4. Goldman L, Ausiello DA (2008) Cecil medicine, vol 702. Saunders Elsevier, Philadelphia

    Google Scholar 

  5. Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, Sharif S-K, Asghari-Jafarabadi M, Zavvari S (2014) Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition 30(4):430–435

    Article  CAS  PubMed  Google Scholar 

  6. Tobón GJ, Youinou P, Saraux A (2010) The environment, geo-epidemiology, and autoimmune disease: rheumatoid arthritis. J Autoimmun 35(1):10–14

    Article  PubMed  Google Scholar 

  7. Eerola E, Möttönen T, Hannonen P, Luukkainen R, Kantola I, Vuori K, Tuominen J, Toivanen P (1994) Intestinal flora in early rheumatoid arthritis. Rheumatology 33(11):1030–1038

    Article  CAS  Google Scholar 

  8. McCulloch J, Lydyard PM, Rook GAW (1993) Rheumatoid arthritis: how well do the theories fit the evidence? Clin Exp Immunol 92(1):1–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Scher JU, Abramson SB (2011) The microbiome and rheumatoid arthritis. Nat Rev Rheumatol 7(10):569–578

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Saarela M, Lähteenmäki L, Crittenden R, Salminen S, Mattila-Sandholm T (2002) Gut bacteria and health foods—the European perspective. Int J Food Microbiol 78(1):99–117

    Article  CAS  PubMed  Google Scholar 

  11. Müller H, de Toledo FW, Resch KL (2001) Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review. Scand J Rheumatol 30(1):1–10

    Article  PubMed  Google Scholar 

  12. Peltonen R, Nenonen M, Helve T, Hänninen O, Toivanen P, Eerola E (1997) Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet. Rheumatology 36(1):64–68

    Article  CAS  Google Scholar 

  13. Mielants H, De Vos M, Cuvelier C, Veys EM (1996) The role of gut inflammation in the pathogenesis of spondyloarthropathies. Acta Clin Belg 51(5):340–349

    Article  CAS  PubMed  Google Scholar 

  14. Danning CL, Boumpas DT (1998) Commonly used disease-modifying antirheumatic drugs in the treatment of inflammatory arthritis: an update on mechanisms of action. Clin Exp Rheumatol 16(5):595–604

    CAS  PubMed  Google Scholar 

  15. Hvatum M, Kanerud L, Hällgren R, Brandtzaeg P (2006) The gut–joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut 55(9):1240–1247

    Article  CAS  PubMed  Google Scholar 

  16. Rad AH, Torab R, Mortazavian AM, Mehrabany EV, Mehrabany LV (2013) Can probiotics prevent or improve common cold and influenza? Nutrition 29(5):805–806

    Article  Google Scholar 

  17. Rad AH, Torab R, Ghalibaf M, Norouzi S, Mehrabany EV (2013) Might patients with immune-related diseases benefit from probiotics? Nutrition 29(3):583–586

    Article  Google Scholar 

  18. Marcason W (2013) Probiotics: where do we stand? J Acad Nutr Diet 113(10):1424

    Article  PubMed  Google Scholar 

  19. Kato I, Endo-Tanaka K, Yokokura T (1998) Suppressive effects of the oral administration of Lactobacillus casei on type II collagen-induced arthritis in DBA/1 mice. Life Sci 63(8):635–644

    Article  CAS  PubMed  Google Scholar 

  20. So J-S, Lee C-G, Kwon H-K, Yi H-J, Chae C-S, Park J-A, Hwang K-C, Im S-H (2008) Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis. Mol Immunol 46(1):172–180

    Article  CAS  PubMed  Google Scholar 

  21. Taneja V (2014) Arthritis susceptibility and the gut microbiome. FEBS Lett 588(22):4244–4249. https://doi.org/10.1016/j.febslet.2014.05.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269

    Article  PubMed  Google Scholar 

  23. Hatakka K, Martio J, Korpela M, Herranen M, Poussa T, Laasanen T, Saxelin M, Vapaatalo H, Moilanen E, Korpela R (2003) Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis—a pilot study. Scand J Rheumatol 32(4):211–215

    Article  CAS  PubMed  Google Scholar 

  24. Mandel DR, Eichas K, Holmes J (2010) Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial. BMC Complement Altern Med 10(1):1

    Article  PubMed  PubMed Central  Google Scholar 

  25. Alipour B, Homayouni-Rad A, Vaghef-Mehrabany E, Sharif SK, Vaghef-Mehrabany L, Asghari-Jafarabadi M, Nakhjavani MR, Mohtadi-Nia J (2014) Effects of Lactobacillus casei supplementation on disease activity and inflammatory cytokines in rheumatoid arthritis patients: a randomized double-blind clinical trial. Int J Rheum Dis 17(5):519–527

    CAS  PubMed  Google Scholar 

  26. de los Angeles Pineda M, Thompson SF, Summers K, de Leon F, Pope J, Reid G (2011) A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Med Sci Monit 17(6):CR347–CR354

    PubMed Central  Google Scholar 

  27. Zamani B, Golkar HR, Farshbaf S, Emadi-Baygi M, Tajabadi-Ebrahimi M, Jafari P, Akhavan R, Taghizadeh M, Memarzadeh MR, Asemi Z (2016) Clinical and metabolic response to probiotic supplementation in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Int J Rheum Dis 19(9):869–879

    Article  CAS  PubMed  Google Scholar 

  28. Vaghef-Mehrabany E, Homayouni-Rad A, Alipour B, Sharif S-K, Vaghef-Mehrabany L, Alipour-Ajiry S (2016) Effects of probiotic supplementation on oxidative stress indices in women with rheumatoid arthritis: a randomized double-blind clinical trial. J Am Coll Nutr 35(4):291–299

    Article  PubMed  Google Scholar 

  29. Malin M, Verronen P, Korhonen H, Syväoja EL, Salminen S, Mykkänen H, Arvilommi H, Eerola E, Isolauri E (1997) Dietary therapy with Lactobacillus GG, bovine colostrum or bovine immune colostrum in patients with juvenile chronic arthritis: evaluation of effect on gut defence mechanisms. Inflammopharmacology 5(3):219–236

    Article  CAS  PubMed  Google Scholar 

  30. Nenonen M, Helve TA, Rauma AL, Hänninen OO (1998) Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. Rheumatology 37(3):274–281

    Article  CAS  Google Scholar 

  31. Shukla A, Gaur P, Aggarwal A (2016) Effect of probiotics on clinical and immune parameters in enthesitis-related arthritis category of juvenile idiopathic arthritis. Clin Exp Immunol 185(3):301–308. https://doi.org/10.1111/cei.12818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Arend WP (2001) Physiology of cytokine pathways in rheumatoid arthritis. Arthritis Care Res 45(1):101–106

    Article  CAS  Google Scholar 

  33. Brzustewicz E, Bryl E (2015) The role of cytokines in the pathogenesis of rheumatoid arthritis—practical and potential application of cytokines as biomarkers and targets of personalized therapy. Cytokine 76(2):527–536

    Article  CAS  PubMed  Google Scholar 

  34. Wolfe F, Cathey MA (1991) The assessment and prediction of functional disability in rheumatoid arthritis. J Rheumatol 18(9):1298–1306

    CAS  PubMed  Google Scholar 

  35. Liu D, Jiang X-Y, Zhou L-S, Song J-H, Zhang X (2016) Effects of probiotics on intestinal mucosa barrier in patients with colorectal cancer after operation: meta-analysis of randomized controlled trials. Medicine 95(15):e3342

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tlaskalová-Hogenová H, Štěpánková R, Hudcovic T, Tučková L, Cukrowska B, Lodinová-Žádnıková R, Kozáková H, Rossmann P, Bártová J, Sokol D (2004) Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 93(2):97–108

    Article  PubMed  Google Scholar 

  37. Wang P, Tao J-H, Pan H-F (2016) Probiotic bacteria: a viable adjuvant therapy for relieving symptoms of rheumatoid arthritis. Inflammopharmacology 24(5):189–196

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Sarah Holloway of the University of North Texas for her thorough critical reading and English editing.

Author information

Author notes

  1. A.T.M., M.K., and A.M.A. contributed equally to this article.

Authors and Affiliations

  1. Faculty of Medicine, Al-Azhar University, Cairo, 11884, Egypt

    Abdelrahman Tarek Mohammed, Mohammed Khattab & Ali Mahmoud Ahmed

  2. Faculty of Medicine, Damascus University, Damascus, Syria

    Tarek Turk

  3. Faculty of Medicine, Menoufia University, Menoufia, Egypt

    Nora Sakr

  4. Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt

    Adham M. Khalil & Mohamed Abdelhalim

  5. Faculty of Medicine, Syrian Private University, Damascus, Syria

    Bisher Sawaf

  6. Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Leading Graduate School Program, and Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Kenji Hirayama

  7. Evidence Based Medicine Research Group and Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam

    Nguyen Tien Huy

  8. Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Leading Graduate School Program, and Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Nguyen Tien Huy

  9. Center for Molecular Bio-Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang, District 5, Ho Chi Minh, 70000, Viet Nam

    Nguyen Tien Huy

Authors
  1. Abdelrahman Tarek Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammed Khattab
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ali Mahmoud Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tarek Turk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nora Sakr
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adham M. Khalil
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohamed Abdelhalim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bisher Sawaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kenji Hirayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nguyen Tien Huy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nguyen Tien Huy.

Ethics declarations

Disclosures

None.

Electronic supplementary material

ESM 1

Supplementary PRISMA checklist. (DOCX 59 kb)

Supplementary Table S2

(DOCX 34 kb)

Supplementary Figure S3

Supplementary figure Forest plot of the change in the clinical and laboratory parameters between probiotics and placebo, A, Change in HAQ, B, Change in the TJC. (JPEG 269 kb)

High Resolution image (TIFF 1797 kb)

Supplementary Table S4

(DOCX 45 kb)

Supplementary Figure S5

Supplementary figure Forest plot of the change in the level of cytokines between probiotics and placebo, A, Change in the level of IL-1β, B, Change in the level of IL-10, C, Change in the level of IL-12, D, Change in the level of TNF-α. (JPEG 367 kb)

High Resolution image (TIFF 2631 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammed, A.T., Khattab, M., Ahmed, A.M. et al. The therapeutic effect of probiotics on rheumatoid arthritis: a systematic review and meta-analysis of randomized control trials. Clin Rheumatol 36, 2697–2707 (2017). https://doi.org/10.1007/s10067-017-3814-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-017-3814-3

Keywords

Search

Navigation