Effects of gut microbiota-targeted interventions on pain, physical function, and inflammatory biomarkers in osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

Gut microbiota dysbiosis has been implicated in osteoarthritis (OA) through the gut-joint axis, but the clinical efficacy of gut microbiota-targeted interventions remains unclear. This systematic review and meta-analysis evaluated the effects of these interventions on clinical outcomes and inflammatory biomarkers in OA.

METHODS

PubMed, Embase, Web of Science, CNKI, and Wanfang were searched from inception to 20 January 2026 for randomized controlled trials (RCTs) of probiotics, prebiotics, synbiotics, or dietary modification in adults with OA. Primary outcomes were visual analog scale (VAS) pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, WOMAC function, and WOMAC total score; secondary outcomes included WOMAC stiffness, body weight, knee flexion angle, cartilage oligomeric matrix protein (COMP), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin (IL)-1β, and IL-6. Standardized mean differences (SMDs) with 95% CIs were pooled using random-effects models; risk of bias was assessed with RoB 2.0. Subgroup analyses, univariable meta-regression, trial sequential analysis (TSA), and GRADE were used to grade certainty.

RESULTS

Eighteen RCTs (2,080 participants) were included. Interventions reduced VAS pain (SMD = -0.66, 95% CI: -1.27 to -0.06, P = 0.03), WOMAC pain (SMD = -0.62, 95% CI: -0.97 to -0.27, P = 0.004), WOMAC function (SMD = -0.40, 95% CI: -0.64 to -0.17, P = 0.0006), and WOMAC total score (SMD = -0.78, 95% CI: -1.26 to -0.30, P = 0.009) and lowered hs-CRP, ESR, and IL-1β. WOMAC stiffness, WOMAC physical function, body weight, knee flexion angle, COMP, and IL-6 did not differ significantly. All 18 trials were rated "some concerns" overall on RoB 2.0. Probiotics showed larger effects than dietary interventions, with appreciable residual heterogeneity. Information accrual reached the required size only for WOMAC pain and WOMAC function; VAS pain, WOMAC total score, and hs-CRP were promising but not yet conclusive. GRADE certainty ranged from high (WOMAC function) to very low (VAS pain); unchanged COMP indicates no support for cartilage protection or disease modification.

CONCLUSION

Gut microbiota-targeted interventions, particularly probiotics, may improve pain, physical function, and systemic inflammation in OA. The evidence is compatible with symptomatic benefit but does not support cartilage protection or disease modification. Because certainty ranges from high to very low and information accrual is incomplete for most outcomes, these findings are provisional pending larger standardized RCTs.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/home, identifier CRD42023472181.