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 relationship 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, searching PubMed, Embase, and Cochrane databases 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 development of knee OA. In addition, next generation gene sequencing suggests the presence of microorganisms in the synovial fluid of osteoarthritic knees, and distinct microbiome profiles detected are presumed to play a role in the development of OA. With regard to the gut microbiome, consistent alterations in microbial composition between OA patients and controls are noted, in addition to several associations between certain gut bacteria with OA-related knee pain, patient-reported outcome measure performance, imaging findings, and changes in metabolic and inflammatory pathways. Regarding the joint microbiome, studies revealed increased levels of lipopolysaccharide (LPS) and LPS-binding protein in synovial fluid are associated with activated macrophages, and correlated with worsened osteophyte severity, joint space narrowing, and pain scores in knee OA patients. In addition, studies demonstrated various microbial composition differences in OA patients compared to control, with certain joint microbes directly associated with OA pathogenesis, inflammation, and metabolic dysregulation. Conclusions The gut microbiome-joint axis and joint microbiome shows alterations in microbial composition between osteoarthritic patients and controls. These alterations are associated with perturbations of metabolic and inflammatory pathways, imaging findings, osteoarthritis-related pain, and patient reported outcome measure performance. Level of Evidence Systematic Review; Level III.