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The microbiome has recently emerged as a powerful contributor to health and illness in chronic, systemic disorders. Furthermore, new microbiome niches beyond traditional gut locations are frequently being described. Over the past 5 years, numerous pivotal studies have demonstrated associations between changes in various microbiome niches and the development of osteoarthritis (OA). Herein, we review the most impactful recent literature, including microbiome associations with disease and the potential therapeutic value of microbiome manipulation.