The Gut-Joint Axis in Hip Osteoarthritis: Distinct Articular Microbial Profiles and Metabolic Potential Compared With
Pablo A Slullitel1, Florencia A Lohmann2, Agustín F Albani-Forneris1
1"Sir John Charnley" Hip Surgery Unit, Institute of Orthopaedics "Carlos E. Ottolenghi", Italian Hospital of Buenos Aires, Buenos Aires, Argentina.
Background:
Intestinal dysbiosis and systemic microbial translocation potentially contribute to chronic joint inflammation. However, the role of the gut-joint axis in the genesis of osteoarthritis still needs to be elucidated. This investigation characterized taxonomic signatures and proinflammatory metabolic pathways within the hip joint to define their contribution to the pathophysiology of osteoarthritis relative to nonarthritic controls.
Methods:
A prospective cohort of 48 patients undergoing hip arthroplasty was enrolled. Specimens including synovial fluid, articular cartilage, and acetabular fossa tissue were collected from patients with primary hip osteoarthritis (n = 20) and femoral neck fracture (n = 20). Metagenomic profiling was performed using 16S-rRNA gene sequencing (V3-V4 region). Alpha and beta diversity, taxonomic composition, and predicted functional pathways (PICRUSt2) were compared based on diagnosis (arthritis vs. fracture) and sample location.
Results:
Osteoarthritic samples demonstrated reduced alpha diversity evenness compared with fracture controls (p = 0.031). While beta diversity was primarily driven by specimen type rather than diagnosis, significant taxonomic differences were observed at the genus level. Pseudomonas, Atopostipes, and Staphylococcus showed significant differential abundance between groups, both by specimen location and diagnosis. Functional predictive analysis revealed a marked enrichment of the KDO2-lipid A biosynthesis pathway in osteoarthritic specimens, specifically within the genus Pseudomonas. Key genes involved in lipopolysaccharide biosynthesis and export, including lpxB, lpxL, and lpxM, exhibited significantly higher median abundances in osteoarthritic joints compared with controls (p < 0.00000001).
Conclusions:
Patients with hip osteoarthritis exhibited specific taxonomic and predicted lipopolysaccharide-related pathways differences compared with nonarthritic controls, consistent with microbial molecular signatures in a noninfectious inflammatory joint environment, despite the absence of major diagnosis-driven community-level differences.
Level Of Evidence:
Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
