The effect of multi-strain probiotics on frailty in osteoarthritis patients: a randomized trial focusing on intestinal leak repair.

BACKGROUND

Increased intestinal permeability may underlie frailty in osteoarthritis (OA), yet targeted treatments remain limited. This trial evaluates whether multi-strain probiotics can reduce plasma zonulin and improve physical frailty in OA patients.

METHODS

In a double-blind, 14-week randomized trial, 110 OA patients (aged 45-70) received either daily multi-strain probiotics (Vivomix containing 112 billion CFUs from eight well-characterized strains, n = 54) or placebo (n = 56). Measurements were taken at baseline and again after 14-week duration. The principal statistical endpoint was the variation in plasma zonulin levels, reflecting intestinal permeability, whereas the clinical primary outcome was variation in frailty status using Fried's criteria. Secondary outcome measurements were pain intensity, Oxford Knee Score, handgrip strength (HGS), gait speed, knee range of motion (ROM), inflammatory and oxidative stress biomarkers (hsCRP, 8-isoprostanes), and safety.

RESULTS

Following participant dropout, 103 individuals were analysed; placebo (n = 54) and probiotic (n = 49). Multi-strain probiotic supplementation significantly reduced frailty scores, plasma zonulin, walking-related pain, and disease severity, and improved HGS and gait speed (p < 0.05). No considerable alterations were detected in ROM, pain at rest, or levels of 8-isoprostanes. Correlation analysis showed a stronger association between frailty and plasma zonulin in the probiotic group after 14 weeks (r² = 0.273, p < 0.05) than in the placebo group (r² = 0.073, p = 0.048) and baseline (r² = 0.058, p = 0.014).

CONCLUSION

Multi-strain probiotic supplementation reduces frailty in OA patients likely by improving intestinal barrier integrity. Findings are specific to Vivomix® and not broadly applicable to all probiotics.

TRIAL REGISTRATION: This study was retrospectively registered in Open Science Framework (OSF), registration date (10th August 2025), and URL for protocol ( https://osf.io/registries/my-registrations ).