Objective: To evaluate the potential for identifying overweight people at risk for osteoarthritis from a gut microbiome biomarker. Background: Osteoarthritis (OA) is the most common form of arthritis, affecting millions of people worldwide. Being overweight increases the load placed on the joints such as the knee, which increases stress and could hasten the breakdown of cartilage. Identifying overweight people at risk for osteoarthritis remains a challenge. However, emerging evidence indicates that microbial dysbiosis in the human gut might play an important role in many inflammatory diseases. Considering the role of inflammation in OA development, analysis of the gut microbiome might be a potential non-invasive tool for overweight individuals to evaluate their risk for OA. Results: In this prospective study, we collected 182 stool samples from overweight OA patients (n = 86) and overweight normal people (n = 96) (25 kg/m2