Effects of probiotics supplementation on rheumatoid arthritis patients: an umbrella review of meta-analyses of randomized controlled trials

Mahsa Ranjbar^1*Abdelmonem Siddiq²Sheida Zeraattalab-Motlagh³Maryam Fallah¹Kurosh Djafarian^1,4Hamed Mohammadi¹Sakineh Shab-Bidar^1,4*

• ¹Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran, Tehran, Alborz, Iran
• ²Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
• ³University of Houston, Houston, Texas, United States
• ⁴Sports and Exercise Medicine Research Center, Tehran University of Medical Sciences, Tehran, Alborz, Iran

Background: Probiotics have been investigated for their potential to improve various diseases, particularly autoimmune diseases. Several systematic reviews and meta-analyses (SRMAs) have examined the impacts of probiotics on the outcomes of patients with rheumatoid arthritis (RA). Nevertheless, the overall strength and quality of this evidence have not been thoroughly compiled or analyzed in detail. Methods: A systematic search was conducted using PubMed, Scopus, and Web of Science until October 2023. Mean differences (MD) and 95% confidence intervals (CI) for each outcome were pooled. Results: Seven SMRAs met the inclusion criteria. From these, eight randomized controlled trials (RCTs) were identified. The results of this umbrella review revealed that probiotic supplementation has a significantly beneficial effect for high-sensitivity C-reactive protein (hs-CRP) (MD: -1.37, 95%CI: -2.15, -0.58), swollen joint count (SJC) (MD: -0.33, 95%CI: -0.58, -0.08), tender joint count (TJC) (MD: -0.38, 95%CI: -0.63, -0.13), , interleukin (IL) 6 (MD: -1.11, 95%CI: -1.62, -0.6), IL-10 (MD: 0.65, 95%CI: 0.46, 0.85), , and IL-12 (MD: -0.89, 95%CI: -1.4, -0.39), and tumor necrosis factor alpha (TNF-α) (MD: -0.62, 95%CI: -0.92, -0.32), (P-value < 0.05 for all). Furthermore, the disease activity score-28 (DAS-28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels showed significant changes; however, due to extreme heterogeneity, a summary effect measure could not be calculated meaningfully for these outcomes. The results of IL-1β revealed insignificant results (P-value > 0.05). Conclusion: Probiotics may be considered for the management of RA, but due to current results, their effects are clinically insignificant. However, due to the low certainty of the current evidence, further well-designed RCTs focusing on specific, well-characterized strains and adequate dosages are necessary to validate these findings.