Intranasal Bacterial Therapeutics Reduce Colonization by the Respiratory Pathogen Mannheimia haemolytica in Dairy Calves

Six strains originating from the nasopharyngeal microbiota of cattle were previously characterized and identified as candidate bacterial therapeutics (BTs) for mitigating the bovine respiratory pathogen In the present study, these BT strains were evaluated for their potential to (i) reduce nasal colonization by (ii) modulate the nasal microbiota, and (iii) stimulate an immune response in calves experimentally challenged with Twenty-four Holstein bull calves (1 to 3 weeks old) received either an intranasal BT cocktail containing 6 strains (3 × 10 CFU per strain; BT + Mh group) 24 h prior to intranasal challenge (3 × 10 CFU) or no BTs prior to challenge (Mh, control group). Nasal swab, blood, and transtracheal aspiration samples were collected over the course of 16 days after BT inoculation. Counts of were determined by culturing, and the nasal and tracheal microbiotas were evaluated using 16S rRNA gene sequencing. Serum cytokines (interleukin-6 [IL-6], IL-8, and IL-10) were quantified by enzyme-linked immunosorbent assay (ELISA). Administration of BT reduced nasal colonization by ( 0.02), modified the composition and diversity of the nasal microbiota, and altered interbacterial relationships among the 10 most relatively abundant genera. The BT + Mh calves also had a lower relative abundance of in the trachea ( 0.01) but similar cytokine levels as Mh calves. This study demonstrated that intranasal BTs developed from the bovine nasopharyngeal spp. were effective in reducing nasal colonization by in dairy calves. Bovine respiratory disease (BRD) is one of the significant challenges for the modern dairy industry in North America, accounting for 23 to 47% of the total mortality among pre- and postweaned dairy heifers. Mass medication with antibiotics is a common practice to control BRD in dairy cattle. However, the emergence of multidrug-resistant BRD pathogens highlights the importance of developing alternatives to antibiotics for BRD mitigation. Using a targeted approach, we recently identified 6 strains originating from the bovine respiratory microbiota as candidates to be used as bacterial therapeutics (BTs) for the mitigation of the BRD pathogen Here, we demonstrated that intranasal inoculation of the BT strains reduced nasal colonization by in dairy calves experimentally challenged with this pathogen. This study, for the first time, shows the potential use of intranasal BTs as an alternative to mitigate BRD pathogens in cattle.