{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:12:12Z","timestamp":1791616332038,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T00:00:00Z","timestamp":1736640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u201cwear and tear\u201d 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 \u201cobservational studies\u201d. 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 reported an association between different tryptophan metabolites and pain levels in patients with OA. Two other studies\u00a0demonstrated a correlation between lipopolysaccharide levels and pain in OA. A fifth study\u00a0confirmed the relationship between Streptococcus relative abundance of Streptococcus spp. and knee pain. These results were not supported by a meta-analysis, which found no significant association between the presence of pain in OA and the presence of bacilli of the genus Streptococcus or plasma markers of the tryptophan pathway. Conclusions: Current evidence indicates a potential link between gut microbiome dysbiosis and OA-related pain. However, methodological limitations preclude definitive conclusions. Further research using advanced techniques and larger cohorts is needed to validate and extend these findings and elucidate the underlying mechanisms. Targeted manipulation of the gut microbiome may be a valuable strategy for pain management in OA patients.<\/jats:p>","DOI":"10.3390\/nu17020264","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T05:40:40Z","timestamp":1736746840000},"page":"264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Relationship Between the Gut Microbiome, Tryptophan-Derived Metabolites, and Osteoarthritis-Related Pain: A Systematic Review with Meta-Analysis"],"prefix":"10.3390","volume":"17","author":[{"given":"Erika","family":"Mel\u00e9ndez-Oliva","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Diet\u00e9tica Aplicada, Nutrici\u00f3n y Composici\u00f3n Corporal (DANuC), Department of Optics, Pharmacology and Anatomy, University of Alicante, 03690 Alicante, Spain"},{"name":"Grupo de Investigaci\u00f3n en Calidad de Vida y Salud, Departamento de Ciencias de la Salud, Universidad Europea de Valencia, 03016 Alicante, Spain"},{"name":"Physiotherapy and Orofacial Pain Working Group, Sociedad Espa\u00f1ola de Disfunci\u00f3n Craneomandibular y Dolor Orofacial (SEDCYDO), 28009 Madrid, Spain"},{"name":"Interdisciplinary Research Group on Musculoskeletal Disorders, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Od\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4804-550X","authenticated-orcid":false,"given":"Oliver","family":"Mart\u00ednez-Pozas","sequence":"additional","affiliation":[{"name":"Physiotherapy and Orofacial Pain Working Group, Sociedad Espa\u00f1ola de Disfunci\u00f3n Craneomandibular y Dolor Orofacial (SEDCYDO), 28009 Madrid, Spain"},{"name":"Interdisciplinary Research Group on Musculoskeletal Disorders, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Od\u00f3n, Spain"},{"name":"Escuela Internacional de Doctorado, Faculty of Health Sciences, Universidad Rey Juan Carlos, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3692-5748","authenticated-orcid":false,"given":"Pierluigi","family":"Sinatti","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Group on Musculoskeletal Disorders, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Od\u00f3n, Spain"},{"name":"IPPOCRATE Centro Medico Specialistico, Via La Spezia 38, 00055 Ladispoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0937-0994","authenticated-orcid":false,"given":"Carmen","family":"Mart\u00edn Carreras-Presas","sequence":"additional","affiliation":[{"name":"Special Care Dentistry, Oral Medicine and Quality of Life Research Gorup (SOUL), Oral Medicine Unit, Faculty of Dentistry, European University of Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Nicol\u00e1s","family":"Cuenca-Zald\u00edvar","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Group on Musculoskeletal Disorders, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Od\u00f3n, Spain"},{"name":"Grupo de Investigaci\u00f3n en Fisioterapia y Dolor, Departamento de Fisioterapia, Facultad de Enfermer\u00eda y Fisioterapia, Universidad de Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Research Group in Nursing and Health Care, Puerta de Hierro Health Research Institute-Segovia de Arana (IDIPHISA), 28222 Majadahonda, Spain"},{"name":"Physical Therapy Unit, Primary Health Care Center \u00abEl Abaj\u00f3n\u00bb, 28231 Las Rozas de Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2345-9482","authenticated-orcid":false,"given":"Silvia","family":"Turroni","sequence":"additional","affiliation":[{"name":"Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0254-6501","authenticated-orcid":false,"given":"Eleuterio A.","family":"S\u00e1nchez Romero","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Calidad de Vida y Salud, Departamento de Ciencias de la Salud, Universidad Europea de Valencia, 03016 Alicante, Spain"},{"name":"Physiotherapy and Orofacial Pain Working Group, Sociedad Espa\u00f1ola de Disfunci\u00f3n Craneomandibular y Dolor Orofacial (SEDCYDO), 28009 Madrid, Spain"},{"name":"Interdisciplinary Research Group on Musculoskeletal Disorders, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Od\u00f3n, Spain"},{"name":"Research Group in Nursing and Health Care, Puerta de Hierro Health Research Institute-Segovia de Arana (IDIPHISA), 28222 Majadahonda, Spain"},{"name":"Faculty of Medicine, Health and Sports, Department of Physiotherapy, Universidad Europea de Madrid, 28670 Villaviciosa de Od\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,12]]},"reference":[{"key":"ref_1","unstructured":"(2024, October 05). 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