The Gut Microbiome and Joint Microbiome Show Alterations in Patients With Knee Osteoarthritis Versus Controls: A Systematic Review

Purpose: To assess the current scientific literature on the microbiome's relation with knee osteoarthritis (OA), with specific focuses on the gut microbiome–joint axis and joint microbiome–joint axis. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines; the PubMed, Embase, and Cochrane databases were searched for relevant English-language clinical studies on the gut and/or joint microbiomes’ association with knee OA in humans. Bias was evaluated using the Methodological Index for Non-randomized Studies score. Results: Thirty-five thousand bacterial species comprise the gut microbiome; approximately 90% are members of the phyla Bacteroides and Firmicutes. Symbiosis between the gut microbiome and host under normal physiological conditions positively affects host growth, development, immunity, and longevity. Gut microbiome imbalance can negatively influence various physiological processes, including immune response, inflammation, metabolism, and joint health including the development of knee OA. In addition, next-generation gene sequencing suggests the presence of microorganisms in the synovial fluid of OA knees, and distinct microbiome profiles detected are presumed to play a role in the development of OA. Regarding the gut microbiome, consistent alterations in microbial composition between OA patients and controls are noted, in addition to several associations between certain gut bacteria and OA-related knee pain, patient-reported outcome measure performance, imaging findings, and changes in metabolic and inflammatory pathways. Regarding the joint microbiome, studies have revealed that increased levels of lipopolysaccharide and lipopolysaccharide-binding protein in synovial fluid are associated with activated macrophages—and are correlated with worsened osteophyte severity, joint space narrowing, and pain scores in knee OA patients. In addition, studies have shown various microbial composition differences in OA patients compared with controls, with certain joint microbes directly associated with OA pathogenesis, inflammation, and metabolic dysregulation. Conclusions: The gut microbiome–joint axis and joint microbiome show alterations in microbial composition between patients with OA and controls. These alterations are associated with perturbations of metabolic and inflammatory pathways, imaging findings, OA-related pain, and patient-reported outcome measure performance. Level of Evidence: Level III, systematic review of Level II and III studies.