S2137 Impact of Probiotic Supplementation on Neurological and Metabolic Outcomes in Relapsing Remitting Multiple Sclerosis: A Meta-Analysis

Introduction: Multiple sclerosis (MS), particularly the relapsing-remitting subtype (RRMS), is influenced by complex interactions involving immune dysregulation, neuroinflammation, oxidative stress, and metabolic disturbances. Emerging evidence suggests that probiotic supplementation may help modulate these pathways, offering potential therapeutic value beyond conventional immunomodulatory treatments. This meta-analysis aims to assess the efficacy and safety of oral probiotics compared to placebo in improving neurological disability, mood symptoms, oxidative stress markers, and metabolic parameters in adults with RRMS. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing probiotics to placebo in adults with RRMS was conducted. Searches were performed in PubMed, Cochrane CENTRAL, Web of Science, Embase, and Scopus through November 12, 2024. Primary outcomes included Expanded Disability Status Scale (EDSS) and mental health indices (BDI-II, DASS, GHQ-28). Secondary outcomes included inflammatory (TNF-α, IL-6), oxidative (nitric oxide, MDA, TAC), and metabolic markers (fasting insulin, HOMA-IR, QUICKI). Standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI) were calculated using random-effects models. Statistical analysis was performed using Review Manager (RevMan) version 5.4. Results: Five randomized controlled trials comprising 288 patients were included, with 144 patients receiving probiotics and 144 receiving placebo, over a treatment duration of 12 to 24 weeks. Probiotics significantly reduced EDSS (SMD = –6.52; 95% CI: –12.96 to –0.08; P = 0.05), BDI-II (SMD = –3.72; P < 0.001), and DASS (SMD = –3.75; P < 0.001). Nitric oxide levels increased (SMD = 8.20; P = 0.01). Improvements in insulin sensitivity were observed (fasting insulin: SMD = –4.45; P = 0.005; HOMA-IR: SMD = –3.59; P < 0.001; QUICKI: SMD = 3.67; P = 0.003). TNF-α levels decreased (SMD = –1.05; P < 0.001), and GHQ-28 scores improved modestly (MD = –2.63; P = 0.04). No significant effects were noted for hs-CRP, IL-6, MDA, or TAC. Conclusion: Probiotics may improve neurological disability, mood, nitric oxide levels, and insulin sensitivity in RRMS while maintaining safety. Despite high heterogeneity in some outcomes, findings support probiotics as a potential adjunctive strategy. Larger, multicenter trials with standardized formulations are warranted.