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Relationship Between the Gut Microbiome, Tryptophan-Derived Metabolites, and Osteoarthritis-Related Pain: A Systematic Review with Meta-Analysis

Erika Meléndez-Oliva, Oliver Martínez-Pozas, P. Sinatti, Carmen Martín Carreras-Presas, J. Cuenca-Zaldívar, S. Turroni, E. A. Sánchez Romero

Nutrients, 2025

528 participants · 41 citations

Abstract

Introduction: Osteoarthritis (OA) is the most prevalent form of arthritis and affects over 528 million people worldwide. Degenerative joint disease involves cartilage degradation, subchondral bone remodeling, and synovial inflammation, leading to chronic pain, stiffness, and impaired joint function. Initially regarded as a “wear and tear” condition associated with aging and mechanical stress, OA is now recognized as a multifaceted disease influenced by systemic factors such as metabolic syndrome, obesity, and chronic low-grade inflammation. Recent studies have focused on the gut-joint axis to investigate how the gut microbiome modulates inflammation and pain in OA. Materials and Methods: A systematic review was conducted following the PRISMA guidelines and was registered with PROSPERO (CRD42024556265). This review included studies involving adults with symptomatic OA and analyzed the relationship between the gut microbiome and OA-related pain. Randomized and non-randomized clinical trials, case reports, editorials, and pilot studies were excluded. Searches were performed in PubMed, Cochrane Library, and Web of Science without publication date restrictions, and filtered for “observational studies”. The study selection and data extraction were performed by two independent researchers, and the risk of bias was assessed using appropriate tools. Results: Five observational studies were included in the systematic review, and three were included in the meta-analysis. Two studies…

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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 528 participants or records.

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