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

Knee osteoarthritis (OA) is a prevalent painful degenerative disease lacking effective disease-modifying drugs. The rise in obesity has increased metabolic OA prevalence, underscoring the need for effective management to delay or prevent knee replacement. We previously showed in a randomized, placebo-controlled trial that 16 g/d of oligofructose-enriched inulin for 6 months improved physical function and metabolic health in adults with comorbid knee OA and obesity. Here, we integrated metagenomic and metabolomic analyses to investigate the potential mechanistic pathways prebiotic fiber increased diet-derived carbohydrate availability to gut microbiota, mitigated excessive host-glycan degradation and mucosal barrier disruption, and reduced systemic inflammation and metabolic dysregulation, ultimately enhancing metabolic health and physical performance. Prebiotic intervention conferred protective effects against OA onset and progression in a diet-induced obesity rat model, as evidenced by reduced tibial cartilage degeneration and synovial membrane thickening. Prebiotic-induced shifts in microbiome function explain benefits along the gut-joint axis.