Multiomics insights into the effects of prebiotics on physical function and metabolism in adults with obesity and knee osteoarthritis

Knee osteoarthritis (OA) is a prevalent, painful, degenerative disease lacking effective disease-modifying drugs. The rise in obesity has increased the prevalence of metabolic OA, underscoring the need for effective management to delay or prevent knee replacement. Prebiotics confer improvement in physical function and metabolic health in adults with comorbid knee OA and obesity by unknown mechanisms. Here, we integrated metagenomic and metabolomic analyzes to investigate prebiotic fiber-linked mechanisms along the gut–knee axis. By reshaping the composition and function of the gut microbiota, prebiotics increased diet-derived carbohydrate availability, mitigated excessive host-glycan degradation and mucosal barrier disruption, reduced systemic inflammation and metabolic dysregulation, ultimately enhancing metabolic health and improving physical performance. In a diet-induced obese rat model, prebiotics reduced tibial cartilage degeneration and synovial membrane thickening, conferring protection against OA onset and progression through a common inflammatory pathway. Our findings provide mechanistic evidence supporting the therapeutic potential of prebiotic supplementation as a conservative management in humans and as a preventive approach for obesity-related knee OA in a preclinical rat model, mediated through the gut-joint axis.