
Whether Probiotic Supplementation Benefits Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis
Hudan Pan, Runze Li, Ting Li, Jun Wang, Liang Liu
Engineering ›› 2017, Vol. 3 ›› Issue (1) : 115-121.
Whether Probiotic Supplementation Benefits Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis
Gut and oral microflora are important factors in the pathogenesis and development of rheumatoid arthritis (RA). Recent studies have shown that probiotic supplements have beneficial consequences on experimental arthritis in rats. However, results from randomized clinical trials on the effects of probiotics have not been consistent. The aim of this study was to systematically review the existing evidence for the effects of probiotic intervention in RA. We included randomized controlled trials (RCTs) of RA patients receiving stable treatment with disease-modifying anti-rheumatic drugs (DMARDs) that: ① were combined with additional probiotic supplements or ② were combined with either no additional supplements or only a placebo treatment. Statistical analysis was performed using Review Manager 5.3.3. Six randomized clinical trials were eligible for inclusion in the meta-analysis, with 249 participants in total. The results showed that the probiotic intervention treatment has not yet achieved significant improvement in the American College of Rheumatology 20% improvement criteria (ACR20) score and the disease activity score in 28 joints (DAS28). The laboratory index C-reactive protein (CRP) (mg·L−1) was significantly reduced in the intervention group. The expression of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukine (IL)-1β was also significantly reduced, while IL-10 expression increased in the probiotic intervention groups. This article is the first systematic review and meta-analysis providing a comprehensive assessment of the benefits of treating RA with probiotics. We found that probiotic supplementation may show a limited improvement in RA therapy in existing reports because of a lack of sufficiently high-quality work on the part of clinicians. More multi-centered, large-sample RCTs are needed in order to evaluate the benefits of probiotics in RA treatment.
Rheumatoid arthritis / Intervention / Probiotic supplementation / Systematic review / Meta-analysis
[1] |
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003;423(6937):356–61.
CrossRef
Pubmed
Google scholar
|
[2] |
Mikuls TR. Co-morbidity in rheumatoid arthritis. Best Pract Res Clin Rheumatol 2003;17(5):729–52.
CrossRef
Pubmed
Google scholar
|
[3] |
Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al.The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 2015;21(8):895–905.
CrossRef
Pubmed
Google scholar
|
[4] |
Kennedy RJ, Kirk SJ, Gardiner KR. Probiotics (Br J Surg 2001; 88: 161–2). Br J Surg 2001;88(7):1018–9.
CrossRef
Pubmed
Google scholar
|
[5] |
O’Toole PW, Cooney JC. Probiotic bacteria influence the composition and function of the intestinal microbiota. Interdiscip Perspect Infect Dis 2008;2008:175285.
CrossRef
Pubmed
Google scholar
|
[6] |
Shinkai S, Toba M, Saito T, Sato I, Tsubouchi M, Taira K, et al.Immunoprotective effects of oral intake of heat-killed Lactobacillus pentosus strain b240 in elderly adults: a randomised, double-blind, placebo-controlled trial. Br J Nutr 2013;109(10):1856–65.
CrossRef
Pubmed
Google scholar
|
[7] |
Shokryazdan P, Faseleh Jahromi M, Navidshad B, Liang JB. Effects of prebiotics on immune system and cytokine expression. Med Microbiol Immunol.Epub 2016 Oct 4.
CrossRef
Pubmed
Google scholar
|
[8] |
Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohn’s Colitis 2014;8(12):1569–81.
CrossRef
Pubmed
Google scholar
|
[9] |
Amdekar S, Roy P, Singh V, Kumar A, Singh R, Sharma P. Anti-inflammatory activity of Lactobacillus on carrageenan-induced paw edema in male Wistar rats. Int J Inflamm 2012;2012:752015.
CrossRef
Pubmed
Google scholar
|
[10] |
Amdekar S, Singh V, Kumar A, Sharma P, Singh R. Lactobacillus casei and Lactobacillus acidophilus regulate inflammatory pathway and improve antioxidant status in collagen-induced arthritic rats. J Interf Cytok Res 2013;33(1):1–8.
CrossRef
Google scholar
|
[11] |
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et alThe American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31(3):315–24.
CrossRef
Pubmed
Google scholar
|
[12] |
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.
CrossRef
Pubmed
Google scholar
|
[13] |
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et alAssessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17(1):1–12.
CrossRef
Pubmed
Google scholar
|
[14] |
Pineda Mde L, Thompson SF, Summers K, de Leon F, Pope J, Reid G. A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Med Sci Monit 2011;17(6):CR347–54.
Pubmed
|
[15] |
Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, Sharif SK, Asghari-Jafarabadi M, Zavvari S. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition 2014;30(4):430–5.
CrossRef
Pubmed
Google scholar
|
[16] |
Hatakka K, Martio J, Korpela M, Herranen M, Poussa T, Laasanen T, et alEffects of probiotic therapy on the activity and activation of mild rheumatoid arthritis−a pilot study. Scand J Rheumatol 2003;32(4):211–5.
CrossRef
Pubmed
Google scholar
|
[17] |
Alipour B, Homayouni-Rad A, Vaghef-Mehrabany E, Sharif SK, Vaghef-Mehrabany L, Asghari-Jafarabadi M, et alEffects of Lactobacillus casei supplementation on disease activity and inflammatory cytokines in rheumatoid arthritis patients: a randomized double-blind clinical trial. Int J Rheum Dis 2014;17(5):519–27.
Pubmed
|
[18] |
Mandel DR, Eichas K, Holmes J. Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial. BMC Complement Altern Med 2010;10:1.
CrossRef
Pubmed
Google scholar
|
[19] |
Zamani B, Golkar HR, Farshbaf S, Emadi-Baygi M, Tajabadi-Ebrahimi M, Jafari P, et alClinical and metabolic response to probiotic supplementation in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Int J Rheum Dis 2016;19(9):869–79.
CrossRef
Pubmed
Google scholar
|
[20] |
Gul’neva MIu, Noskov SM. Colonic microbial biocenosis in rheumatoid arthritis. Klin Med 2011;89(4):45–8.
Pubmed
|
[21] |
Newland PK, Heitkemper M, Zhou Y. The emerging role of the gut microbiome in adult patients with multiple sclerosis. J Neurosci Nurs 2016;48(6):358–64.
CrossRef
Google scholar
|
[22] |
Montoya J, Matta NB, Suchon P, Guzian MC, Lambert NC, Mattei JP, et alPatients with ankylosing spondylitis have been breast fed less often than healthy controls: a case-control retrospective study. Ann Rheum Dis 2016;75(5):879–82.
CrossRef
Pubmed
Google scholar
|
[23] |
Liu J, Kandasamy S, Zhang J, Kirby CW, Karakach T, Hafting J, et alPrebiotic effects of diet supplemented with the cultivated red seaweed Chondrus crispus or with fructo-oligo-saccharide on host immunity, colonic microbiota and gut microbial metabolites. BMC Complement Altern Med 2015;15:279.
CrossRef
Pubmed
Google scholar
|
[24] |
Jørgensen SF, Trøseid M, Kummen M, Anmarkrud JA, Michelsen AE, Osnes LT, et alAltered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol 2016;9(6):1455–65.
CrossRef
Pubmed
Google scholar
|
[25] |
Farkas AM, Panea C, Goto Y, Nakato G, Galan-Diez M, Narushima S, et alInduction of Th17 cells by segmented filamentous bacteria in the murine intestine. J Immunol Methods 2015;421:104–11.
CrossRef
Pubmed
Google scholar
|
[26] |
Joyce SA, Gahan CG. Bile acid modifications at the microbe-host interface: potential for nutraceutical and pharmaceutical interventions in host health. Annu Rev Food Sci Technol 2016;7(1):313–33.
CrossRef
Pubmed
Google scholar
|
[27] |
Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature 2016;535(7610):65–74.
CrossRef
Pubmed
Google scholar
|
[28] |
Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature 2016;535(7610):75–84.
CrossRef
Pubmed
Google scholar
|
[29] |
Morris G, Berk M, Carvalho A, Caso JR, Sanz Y, Walder K, et alThe role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmune disease. Mol Neurobiol.Epub 2016 Jun 27.
CrossRef
Pubmed
Google scholar
|
[30] |
Kim CH, Park J, Kim M. Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw 2014;14(6):277–88.
CrossRef
Pubmed
Google scholar
|
[31] |
Ohno H. Gut microbiota, host defense and immunity: analysis with integrative omics approach. Jpn J Clin Immunol 2014;37(5):403–11. Japanese.
CrossRef
Google scholar
|
[32] |
Smith PM, Howitt MR, Panikov N, MichaudM, Gallini CA, Bohlooly -Y M, et alThe microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013;341(6145):569–73.
CrossRef
Pubmed
Google scholar
|
[33] |
Ericsson AC, Hagan CE, Davis DJ, Franklin CL. Segmented filamentous bacteria: commensal microbes with potential effects on research. Comp Med 2014;64(2):90–8.
Pubmed
|
[34] |
Goto Y, Panea C, Nakato G, Cebula A, Lee C, Diez MG, et alSegmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity 2014;40(4):594–607.
CrossRef
Pubmed
Google scholar
|
[35] |
Mansson I, Colldahl H. The intestinal flora in patients with bronchial asthma and rheumatoid arthritis. Acta Allergol 1965;20:94–104.
CrossRef
Google scholar
|
[36] |
Dearlove SM, Barr K, Neumann V, Isdale A, Bird HA, Gooi HC, et alThe effect of non-steroidal anti-inflammatory drugs on faecal flora and bacterial antibody levels in rheumatoid arthritis. Br J Rheumatol 1992;31(7):443–7.
CrossRef
Pubmed
Google scholar
|
[37] |
Kohashi O, Kuwata J, Umehara K, Uemura F, Takahashi T, Ozawa A. Susceptibility to adjuvant-induced arthritis among germfree, specific-pathogen-free, and conventional rats. Infect Immun 1979;26(3):791–4.
Pubmed
|
[38] |
Liu X, Zeng B, Zhang J, Li W, Mou F, Wang H, et alRole of the gut microbiome in modulating arthritis progression in mice. Sci Rep 2016;6:30594.
CrossRef
Pubmed
Google scholar
|
[39] |
Fuller R. Probiotics in man and animals. J Appl Bacteriol 1989;66(5):365–78.
CrossRef
Pubmed
Google scholar
|
[40] |
Patel R, DuPont HL. New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clin Infect Dis 2015;60(Suppl 2):S108–21.
CrossRef
Pubmed
Google scholar
|
[41] |
He B, Hoang TK, Wang T, Ferris M, Taylor CM, Tian X, et alResetting microbiota by Lactobacillus reuteri inhibits Treg deficiency-induced autoimmunity via adenosine A2A receptors. J Exp Med 2017;214(1):107–23.
CrossRef
Pubmed
Google scholar
|
[42] |
Manuzak JA, Hensley-McBain T, Zevin AS, Miller C, Cubas R, Agricola B, et alEnhancement of microbiota in healthy macaques results in beneficial modulation of mucosal and systemic immune function. J Immunol 2016;196(5):2401–9.
CrossRef
Pubmed
Google scholar
|
[43] |
Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, et alLinking the human gut microbiome to inflammatory cytokine production capacity. Cell 2016;167(7):1897.
CrossRef
Pubmed
Google scholar
|
/
〈 |
|
〉 |