Targeting the gut–brain axis in migraine: Effects of probiotic supplementation on migraine outcomes and inflammatory markers (CRP and TNF-α)
Abstract
The gut–brain axis has emerged as a potential therapeutic target in migraine management. Several randomized controlled trials (RCTs) have evaluated probiotic supplementation in migraine, yet their findings remain heterogeneous. The aim of this study was to systematically assess and quantitatively synthesize the effects of probiotics on migraine-related outcomes. A systematic review and meta-analysis of randomized controlled trials was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD420261327461). Electronic databases were searched from inception to January 2026. Random-effects meta-analyses were performed to calculate pooled standardized mean differences (SMD) with 95% confidence intervals (CI). Primary outcomes included migraine attack frequency, migraine duration, and migraine severity. Secondary outcomes comprised inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-α). Risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB 2) tool. Six RCTs involving 422 participants were included. Overall, probiotic supplementation significantly improved migraine-related outcomes compared with placebo (p<0.00001). Subgroup analyses demonstrated significant reductions in migraine attack frequency (p=0.002), migraine duration (p=0.0003), migraine severity (p=0.0006), and migraine disability assessment (MIDAS) score (p= 0.04).…
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