Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation

SummaryObjectiveThe microbiome is recognized as a new frontier in medicine with connections to a variety of diseases. We aimed to evaluate the association of lipopolysaccharide (LPS), a key pro-inflammatory product of the microbiome, with severity of inflammation, symptoms and radiographic abnormalities of knee osteoarthritis (OA).DesignLPS was measured using a recombinant Factor C (rFC) assay, carefully optimized for systemic and synovial fluid (SF) analyses. LPS binding protein (LBP) was tested in both serum and SF of 25 patients (31 knees) from the Etarfolatide cohort for association with OA phenotypic outcomes. Models were adjusted for age, gender and body mass index.ResultsBased on LPS spike-and-recovery, both serum and SF dilutions of 0.1% were required to achieve recovery rates of at least 75% in all test specimens. Low coefficients of variation (CVs) (<10%) were achieved with both serum and SF dilutions <0.2%. Serum LPS and LBP were associated with the abundance of activated macrophages in the knee joint capsule and synovium. SF LPS and LBP were associated with the abundance of activated macrophages in the synovium. Serum LPS, LBP and SF LPS were associated with knee osteophyte severity. SF LPS was positively associated with knee joint space narrowing (JSN) severity and total WOMAC score. SF LBP was positively associated with self-reported knee pain score.ConclusionThese data strongly support a role for LPS in the pathogenesis and severity of structural abnormalities and symptoms of knee OA.