Psychological stress and gut microbiota regulation of osteoarthritis progression: mechanisms and therapeutic strategies.

Psychological stress is increasingly recognized as an important contributor to osteoarthritis (OA) progression, yet the underlying mechanisms remain incompletely understood. This review examines the gut microbiota as a potential mediator linking psychological stress to OA progression. Emerging evidence suggests that the gut microbiota is an integral component of the brain-gut-joint axis. Psychological stress may induce microbial dysbiosis, which can in turn contribute to immune dysregulation, metabolic alterations, intestinal barrier dysfunction, and sensitization of pain pathways. Through interconnected local and systemic effects, these changes may aggravate structural joint damage and worsen symptom burden in OA. We synthesize epidemiological, preclinical, and emerging clinical evidence linking psychological stress to OA, and integrate key modulators-including diet, host genetics, medications, and lifestyle factors-to provide a more comprehensive mechanistic framework. We also discuss potential interventions targeting this axis, including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and psychological interventions, which may help slow OA progression and complement conventional OA management. Collectively, these insights provide a rationale for therapeutic approaches targeting the stress-microbiome-osteoarthritis axis, with the potential to improve clinical outcomes in patients with OA.