title: Identification of predictive biomarkers of disease state in transition dairy cows.
abstract: In dairy cows, periparturient disease states, such as metritis, mastitis, and laminitis, are leading to increasingly significant economic losses for the dairy industry. Treatments for these pathologies are often expensive, ineffective, or not cost-efficient, leading to production losses, high veterinary bills, or early culling of the cows. Early diagnosis or detection of these conditions before they manifest themselves could lower their incidence, level of morbidity, and the associated economic losses. In an effort to identify predictive biomarkers for postpartum or periparturient disease states in dairy cows, we undertook a cross-sectional and longitudinal metabolomics study to look at plasma metabolite levels of dairy cows during the transition period, before and after becoming ill with postpartum diseases. Specifically we employed a targeted quantitative metabolomics approach that uses direct flow injection mass spectrometry to track the metabolite changes in 120 different plasma metabolites. Blood plasma samples were collected from 12 dairy cows at 4 time points during the transition period (-4 and -1 wk before and 1 and 4 wk after parturition). Out of the 12 cows studied, 6 developed multiple periparturient disorders in the postcalving period, whereas the other 6 remained healthy during the entire experimental period. Multivariate data analysis (principal component analysis and partial least squares discriminant analysis) revealed a clear separation between healthy controls and diseased cows at all 4 time points. This analysis allowed us to identify several metabolites most responsible for separating the 2 groups, especially before parturition and the start of any postpartum disease. Three metabolites, carnitine, propionyl carnitine, and lysophosphatidylcholine acyl C14:0, were significantly elevated in diseased cows as compared with healthy controls as early as 4 wk before parturition, whereas 2 metabolites, phosphatidylcholine acyl-alkyl C42:4 and phosphatidylcholine diacyl C42:6, could be used to discriminate healthy controls from diseased cows 1 wk before parturition. A 3-metabolite plasma biomarker profile was developed that could predict which cows would develop periparturient diseases, up to 4 wk before clinical symptoms appearing, with a sensitivity of 87% and a specificity of 85%. This is the first report showing that periparturient diseases can be predicted in dairy cattle before their development using a multimetabolite biomarker model. Further research is warranted to validate these potential predictive biomarkers.
authors.affiliation: Department of Agricultural, Food and Nutritional Science, Edmonton, Alberta, Canada T6G 2P5.
authors.forename: D
authors.initials: D
authors.lastname: Hailemariam
authors.affiliation: Departments of Computer and Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2M9.
authors.forename: R
authors.initials: R
authors.lastname: Mandal
authors.affiliation: Departments of Computer and Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2M9.
authors.forename: F
authors.initials: F
authors.lastname: Saleem
authors.affiliation: Department of Agricultural, Food and Nutritional Science, Edmonton, Alberta, Canada T6G 2P5.
authors.forename: S M
authors.initials: SM
authors.lastname: Dunn
authors.affiliation: Departments of Computer and Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2M9.
authors.forename: D S
authors.initials: DS
authors.lastname: Wishart
authors.affiliation: Department of Agricultural, Food and Nutritional Science, Edmonton, Alberta, Canada T6G 2P5. Electronic address: burim.ametaj@ualberta.ca.
authors.forename: B N
authors.initials: BN
authors.lastname: Ametaj
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D007774:Lactation; D008137:Longitudinal Studies; D008244:Lysophosphatidylcholines / Q000097:blood; D036801:Parturition; D049590:Postpartum Period; D011644:Puerperal Disorders / Q000097:blood / Q000662:veterinary*
chemical_list: D015415:Biomarkers; D008244:Lysophosphatidylcholines; C003223:propionylcarnitine; D002331:Carnitine
keywords: dairy cow; periparturient disease; plasma metabolite; predictive biomarker