Applied nutritional investigationProbiotic supplementation improves inflammatory status in patients with rheumatoid arthritis
Introduction
Rheumatoid arthritis (RA) is a relatively common disabling autoimmune disease that is characterized by progressive joint disorder, significant pain, and functional disability. This systemic inflammatory disease of unknown cause has a prevalence of 0.5% to 1% among adults worldwide and continues to cause significant morbidity and premature mortality [1], [2]. Although many effective pharmacologic agents are available today to alleviate RA symptoms, side effects have been reported to accompany the benefits derived from these therapies [1], [3]. In addition, therapies that target the modifiable probable underlying causes of RA and that may most efficiently bring the disease under control are still being sought. There is some evidence from human studies that gut microbiota is altered in patients with RA and that imbalanced gut microbiota may contribute to the initiation of the disease [4], [5], [6], [7].
As defined by the Food and Agriculture Organization of the United Nations and the World Health Organization, probiotics are “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” [8]. Probiotics have been suggested to be effective against a number of disorders, and the modulation of immune system function is among the most studied properties of probiotics. Many in vivo and in vitro studies have demonstrated that some strains of probiotics can either stimulate or downregulate immune system function in a strain- and dose-specific manner; patients with diseases that result from downregulated immune systems may benefit from the first property, whereas those with hyperactive immune systems may profit from the probiotic strains that cause such downregulation [9], [10].
The effect of probiotic administration for either the prevention or treatment of RA has been investigated in a limited number of animal and human studies. Animals fed Lactobacillus casei had improved clinical manifestations, reduced proinflammatory cytokines (i.e., interleukins-1 β, 2, 6, 12, and 17 [IL-1 β, IL-2, IL-6, IL-12, and IL-17, respectively], interferon-γ [IFN-γ], and tumor necrosis factor-α [TNF-α]), and increased regulatory cytokines (interleukin-10 [IL-10] and transforming growth factor-β [TGF-β]) [11], [12], [13], [14]. Yogurts fermented with Lactobacillus bulgaricus and live or sacrificed Lactobacillus rhamnosus GG (LGG) reduced arthritis clinical scores in Lewis rats [15]. Escherichia coli strain O83 (Colinfant), when administered in combination with methotrexate, significantly inhibited both inflammation and destructive arthritis-associated changes [16]. Human studies have applied different strains of probiotics, and all have reported functional improvement or subjective well-being in those receiving the treatment. However, disease activity or inflammatory biomarkers were not significantly modified by the interventions [17], [18], [19]. The aim of the present randomized clinical trial was to investigate the effects of L. casei 01 supplementation on the disease activity and inflammatory cytokines of patients with RA.
Section snippets
Subjects
The target population of the present study was women with RA who were referred to the rheumatology clinic of Sina Hospital in Tabriz, Iran, or Sheykholrayis Polyclinic in Tabriz, Iran. A rheumatologist listed patients who had been to her office who met the inclusion criteria and recorded their phone numbers. Subjects were contacted a day before commencing the supplementation, and the study was thoroughly explained to them. Patients entered the study if they were interested. The inclusion
Results
Sixty female patients with RA were recruited in the present clinical trial, and of these 60, 46 women completed the study: 10 patients (6 in the probiotic group and 4 in the placebo group) withdrew from the study for reasons irrelevant to the treatment (i.e., not willing to continue the treatments, being on vacation, having changed their location and thus not accessible), and 4 patients (2 in the probiotic group and 2 in the placebo group) were dropped out of analyses because they had not
Discussion
The results of the present study showed that 8 wk of L. casei 01 supplementation reduced disease activity and proinflammatory cytokines (TNF-α, IL-6, and IL-12) while at the same time increasing the regulatory cytokine (IL-10) in patients with RA. IL-1 β was not significantly affected by the intervention. The IL-10/IL-12 proportion significantly increased in the probiotic group. However, the IL-10/IL-6 and IL-10/IL-TNF-α proportions were not significantly different between the two groups at the
Conclusions
This study demonstrated that L. casei 01 could improve disease activity and inflammation in patients with RA and suggested that this probiotic may be a beneficial adjunct therapy in this population of patients if the results are confirmed by future studies. It also indicates that different strains of L. casei and other species with various dosages should be studied.
Acknowledgments
The present study was funded by the Vice Chancellor for Research of Tabriz University of Medical Sciences in Tabriz, Iran. We sincerely thank Dr. Davood Hasanzadeh for his precious comments on the preparation process of study capsules. The authors would also like to thank the Drug Applied Research Center of Tabriz University of Medical Sciences in Tabriz, Iran, for supporting the laboratory tests needed for this study.
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E.V.M. conceived and designed the study; generated, collected, assembled, analyzed, and interpreted the data; and drafted and revised the manuscript. B.A. generated and collected the data. A.H.R. conceived and designed the study; analyzed and interpreted the data; and approved the final version of the manuscript. S.K.S. generated and collected the data. M.A.J. analyzed the data. S.Z. collected the data.