A Single Intranasal Dose of Bacterial Therapeutics to Calves Confers Longitudinal Modulation of the Nasopharyngeal Microbiota

To address the emergence of antimicrobial-resistant pathogens in livestock, microbiome-based strategies are increasingly being sought to reduce antimicrobial use. Here, we describe the intranasal application of bacterial therapeutics (BTs) for mitigating bovine respiratory disease (BRD) and used structural equation modeling to investigate the causal networks after BT application. Beef cattle received i) an intranasal cocktail of previously characterized BT strains, ii) an injection of metaphylactic antimicrobial (tulathromycin), or iii) intranasal saline. Despite being transient colonizers, inoculated BT strains induced longitudinal modulation of the nasopharyngeal bacterial microbiota while showing no adverse effect on animal health. The BT-mediated changes in bacteria included reduced diversity and richness and strengthened cooperative and competitive interactions. In contrast, tulathromycin increased bacterial diversity and antibiotic resistance, and disrupted bacterial interactions. Overall, a single intranasal dose of BTs can modulate the bovine respiratory microbiota, highlighting that microbiome-based strategies have the potential in being utilized to mitigate BRD in feedlot cattle.