NMR-based metabolomics of plasma from dairy calves infected with two primary causal agents of bovine respiratory disease (BRD)

Authors: SHENG, QINGYU - Mississippi State University; SANTOS-RIVERA, MARIANA - Mississippi State University; OUYANG, XIAOGUANG - Mississippi State University; KOUBA, ANDREW - Mississippi State University; VANCE, CARRIE - Mississippi State University; FITZKEE, NICHOLAS - Mississippi State University; HILL, REBECCA - Mississippi State University; BAIRD, RICHARD - Mississippi State University; BLAIR, ELLIANNA - Mississippi State University

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2023
Publication Date: 2/15/2023
Citation: Sheng, Q., Santos-Rivera, M., Ouyang, X., Kouba, A.J., Vance, C.K., Fitzkee, N., Hill, R., Baird, R., Blair, E. 2023. NMR-based metabolomics of plasma from dairy calves infected with two primary causal agents of bovine respiratory disease (BRD). Scientific Reports. 13:2671-2688. https://doi.org/10.1038/s41598-023-29234-3.
DOI: https://doi.org/10.1038/s41598-023-29234-3

Interpretive Summary: By using 1H-NMR spectroscopy in blood plasma, this study demonstrated that important metabolic shifts are occurring in the host in response to infection with BRSV (viraus) compared to M. haemolytica (bacterial). Following the application of univariate and multivariate statistical methods, the concentration of 46 metabolites changed differentially changed in sick cattle, indicated different metabolic markers for different pathogenens. These metabolites appeared to be critical fuel substrates and products of the energy imbalance occurring during the infections due to signaling cascades and immune response activation. In addition, our findings support the potential of NMR to create metabolic profiles of BRD that contribute to the understanding of the diversity and concentrations of essential metabolites in plasma that can be applied for the further development of novel diagnostic tools.

Technical Abstract: Each year, bovine respiratory disease (BRD) results in significant economic loss in the cattle sector, and novel metabolic profiling for early diagnosis represents a promising tool for developing effective measures for disease management. Here, 1H-nuclear magnetic resonance (1H-NMR) spectra were used to characterize metabolites from blood plasma collected from male dairy calves (n = 10) intentionally infected with two of the main BRD causal agents, bovine respiratory syncytial virus (BRSV) and Mannheimia haemolytica (MH), to generate a well-defined metabolomic profile under controlled conditions. In response to infection, 46 metabolites (BRSV = 32, MH = 33) changed in concentration compared to the uninfected state. Fuel substrates and products exhibited a particularly strong effect, reflecting imbalances that occur during the immune response. Furthermore, 1H-NMR spectra from samples from the uninfected and infected stages were discriminated with an accuracy, sensitivity, and specificity = 95% using chemometrics to model the changes associated with disease, suggesting that metabolic profiles can be used for further development, understanding, and validation of novel diagnostic tools.