SUMMARY Despite the increasing preventative efforts (vaccines, hygiene, pre-conditioning), respiratory tract (RT) infections pose a significant challenge across mammalian species. Recently, there has been a greater emphasis on promoting healthy microbiome colonization to mitigate respiratory infection in humans and livestock species. In livestock animals, especially in cattle, RT microbiome research has mainly focused on characterizing the respiratory tract microbial community in healthy and sick animals, aiming to identify microbiota linked to disease or health status. However, this approach overlooked the dynamics of RT microbiome that comprises commensal opportunistic pathogens (an element of the pathobiome) contributing to the infection and disease pathogenesis. Moreover, there is a lack of attempts to evaluate the interactions among host immunity-microbiome-pathobiome during pathogenesis for the development of successful microbiome-based interventions to improve cattle respiratory health. Recent research has revealed new insights into the gut-lung axis (GLA) and the regulatory role of the gut microbiota in determining host susceptibility or resilience to respiratory infections. Therefore, this review aims to critically discuss the roles of RT microbiome (including pathobiome) and GLA in respiratory health, while elucidating the mechanisms driving the dynamic transition from a commensal state to pathogenic state during microbiome dysbiosis and immune dysregulation, and identifying microbiome targets for RT health improvement.