Serum metabolic fingerprinting of pre-lameness dairy cows by GC-MS reveals typical profiles that can identify susceptible cows

The objectives of this study were to identify metabolite fingerprints in the serum related to amino acid (AA), carbohydrate, and lipid metabolism in transition dairy cows at -8 and -4 wks prior to parturition, at +2 wks postpartum during lameness diagnosis as well as at +4 and +8 wks after parturition. All cases of lameness occurred at around +2 wks after parturition. Out of 100 dairy cows included in this nested case-control study only 6 pregnant multiparous (parity: 3.0 +/- 0.6, Mean +/- SEM) Holstein dairy cows with lameness only and 20 healthy control cows (CON) were selected for serum GC-MS metabolomics analysis. All cows selected were not injured mechanically and had similar parity (3.3 +/- 0.6) and body condition score (BCS). A total of 29 metabolites were identified and quantified in the serum. Results showed that 18 and 15 metabolites differentiated pre-lame cows from CON ones at - 8 and - 4 wks prior to parturition. Ten metabolites were found altered at the week of lameness diagnosis. Of note: pre-lame cows were characterized by greater concentrations of several amino acids including Gly, Leu, Phe, Ser, Val, D-mannose, Myo-inositol, and phosphoric acid (PA) at - 8 and - 4 wks prior to lameness and at the week of lameness diagnosis. At +4 wks after parturition 11 metabolites were altered in lameness cows, and at +8 wks there were 13 metabolites that differentiated the two groups. The high accuracy of the top 6 metabolites at -8 wks prior to parturition or approximately 9-11 wks before lameness diagnosis (Glu, Orn, Phe, Ser, Val, and PA) and another 5 metabolites at -4 wks before parturition, or approximately 5-7 wks before lameness diagnosis (Leu, Orn, Phe, Ser, and D-mannose) suggest that those metabolites may serve as potential monitoring biomarkers of lameness prior to lameness diagnosis. Data also showed multiple alterations during the week of lameness as well as at +4 and +8 wks postpartum suggesting lame cows are not metabolically healthy several weeks after the incidence of lameness. Significance: Lameness is one of the top three health issues of dairy cows in Canada that influences early culling of dairy cows. Despite a few efforts, there is scarcity of data regarding metabolic alterations that precede, associate, and follow lameness. We investigated whether alterations in the metabolite signatures prior, during, and after development of lameness can be used to screen cows for susceptibility to lameness, characterize lameness from the metabolic prospective, and predict the outcome of this economically important health issue of dairy cows. The results demonstrate typical metabotypes as shown by increased serum concentrations of Val, Gly, Ser, Leu, Phe, D-mannose, myo-inositol, and phosphoric acid at - 8 and - 4 wks prior to parturition (or - 6 to -10 wks prior to occurrence of lameness) and at the week of lameness diagnosis.