Bovine respiratory disease (BRD) remains a significant economic challenge in dairy cattle despite extensive vaccination programs that have been developed and implemented during the last few decades. This study investigated the nasopharyngeal microbiome and resistome of dairy cattle across various life stages to understand the roles of microbial communities associated with BRD. A case-control study was conducted on three commercial dairy farms in Northern California, collecting nasopharyngeal swabs from 69 animals, including preweaned calves, weaned heifers, and lactating cows with and without BRD. Shotgun metagenomic sequencing was used to characterize both microbiome and resistome profiles observed at the time of BRD diagnosis. Results revealed that BRD is associated with distinct microbial community patterns, rather than the increased abundance of a specific pathogen. Age was a critical factor influencing microbial diversity, with adult cows showing the highest diversity and weaned heifers with BRD showing the lowest. A total of 1, 164 bacterial species were identified, with BRD cases harboring 14 unique species compared to control animals. BRD cases were characterized by the co-occurrence of multiple respiratory pathogens, including Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mesomycoplasma species, which showed positive correlation with BRD cases but negative correlations in BRD controls, while BRD control animals showed significantly higher abundance of commensal Staphylococcus species. Resistome analysis identified 65 antimicrobial resistance genes, with BRD cases harboring more unique resistance genes than BRD controls. These findings challenge traditional single-pathogen models and demonstrate that BRD is likely the result of complex microbial community interactions and changes in community abundance, providing new potential targets to explore when considering prevention strategies toward promoting microbial communities that prevent or reduce the risk of BRD. IMPORTANCEBovine respiratory disease (BRD) represents one of the most economically challenging conditions in cattle production, with an estimated direct cost that exceeds 165 million annually in the United States alone. Despite decades of vaccination efforts targeting known pathogens, BRD prevalence remains unchanged, indicating an incomplete understanding of disease pathogenesis. This study provides critical insights by shifting focus from individual pathogens to entire microbial communities, revealing that BRD involves complex bacterial interactions, as well as the role of the understudied nasal commensal microbiome in healthy animals. The identification of distinct "pathobiomes" associated with disease and protective commensal communities in healthy animals fundamentally changes approaches to BRD prevention and treatment. The discovery that age significantly influences microbiome stability highlights critical intervention periods. Furthermore, the association between BRD and increased antimicrobial resistance genes raises concerns about current treatment and overall management practices, selecting for drug-resistant communities. This research provides a foundation for developing microbiome-based diagnostic tools and interventions supporting healthy microbial ecosystem development.
Garzon et al. (Tue,) studied this question.