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

European Journal of Clinical Nutrition (2026)Cite this article

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Abstract

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).

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Fig. 1: Flow diagram of patient recruitment, randomization, and follow-up in the clinical trial.
Fig. 2: Effects of Probiotic Supplementation on Frailty Status in Patients with Osteoarthritis.
Fig. 3: Effects of Probiotic Supplementation on Handgrip Strength in Osteoarthritis Patients.
Fig. 4: Effects of Probiotic Supplementation on Gait Speed in Osteoarthritis Patients.
Fig. 5: Correlation between Plasma Zonulin Levels and Frailty Scores in OA Patients.

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Data availability

Data underlying the reported results can be obtained from the corresponding author upon request.

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Funding

Financial support for this research work was provided by the University of Sharjah, UAE, through competitive grant 24010901164 awarded to Asima Karim.

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Authors and Affiliations

  1. Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates

    Asima Karim, Firdos Ahmad & Rizwan Qaisar

  2. Iron Biology Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates

    Asima Karim

  3. Department of Trauma and Orthopaedic Surgery, Rehman Medical Institute, Peshawar, Pakistan

    Haroon Ahmed Khan

  4. Department of Neurology and Stroke Medicine, Rehman Medical Institute, Peshawar, Pakistan

    M. Shahid Iqbal

  5. Cardiovascular Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates

    Firdos Ahmad & Rizwan Qaisar

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Contributions

Conceptualization: AK, RQ, and FA. Data Management and Curation: AK, RQ, HAK, and MSI. Statistical and Formal Analysis: AK, RQ, HAK, and FA. Funding Support: AK. Experimental Investigation: AK, RQ, HAK, and MSI. Methodological design: MSI and HAK. Project oversight and Administration: AK, RQ, HAK, and MSI. Resources: AK, RQ, HAK, and MSI. Supervision: AK and RQ. Validation of Findings: AK, RQ, HAK, and MSI. Manuscript Writing—Original Draft: AK, RQ, and FA. Manuscript Revision & Editing: AK, RQ, HAK, and FA.

Corresponding author

Correspondence to Asima Karim.

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The authors declare no competing interests.

Approval by ethics committee and participant consent

The study ensued the protocols of CONSORT guidelines. The study approval granted by the Medical Research Ethics Committee of RMI (Ref. # RMI-HEC-13-09-45, dated: 7th November 2022). The study executed after securing recorded informed consent from every participant.

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Karim, A., Khan, H.A., Shahid Iqbal, M. et al. The effect of multi-strain probiotics on frailty in osteoarthritis patients: a randomized trial focusing on intestinal leak repair. Eur J Clin Nutr (2026). https://doi.org/10.1038/s41430-026-01719-0

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