BACKGROUND AND AIMS: The impact of dietary live microbe intake on adolescent obesity is still not fully understood. This study aims to investigate the potential relationship between dietary live microbe intake and obesity among U.S adolescents, and to explore the mediating role of physical activity (PA). METHODS AND RESULTS: Data from NHANES (1999-2018) were analyzed, and dietary live microbe intake was categorized into low, medium, and high groups using a developed framework. Survey-weighted logistic regression and mediation analysis models were used to examine the association between live microbe intake and adolescent obesity, as well as the potential mediating effect of PA. Our study included 8443 participants aged 6-18, representing the noninstitutionalized U.S population of 184.5 million. We found that participants with a high dietary intake of live microbes had lower odds of developing obesity compared to those with the lowest exposure to live microbes (AOR = 0.900, 95 % CI: 0.812, 0.997). Additionally, our mediation analysis revealed a significant indirect effect of live microbes on obesity risk through PA (P-value <
0.002), with 39.4 % (95 % CI: 24.5 %, 86.5 %) of the effect mediated by PA. CONCLUSION: Our study highlights the association between consuming a higher amount of live microbes in the diet and a decreased risk of obesity among U.S adolescents. It also suggests that PA may act as a mediator in this relationship. Therefore, it is crucial to emphasize the incorporation of both dietary interventions and PA in the development of prevention and therapy policies for managing adolescent obesity.