Metabolomics-Based Profiling Identifies Serum Signatures That Predict the Risk of Metritis in Transition Dairy Cows

The objectives of this study were to identify metabolite signatures in the blood of dairy cows before, during, and after diagnosis of metritis that could be used to predict the risk of metritis in transition dairy cows. DI/LC-MS/MS was used to analyze serum samples collected from both 20 healthy (CON) and 6 metritic cows during -8, -4, disease diagnosis, +4 and +8 wks relative to parturition. Univariate (Wilcoxon-Mann-Whitney test by R, statistical significance: P < 0.05) and multivariate data (i.e., PCA and PLS-DA; Permutation test for the PLS-DA model: P < 0.05) analyses were conducted to examine alterations of serum metabolites throughout the progress of the disease. Results from univariate analysis indicated that cows with metritis experienced altered concentrations of multiple serum amino acids (AAs), glycerophospholipids, sphingolipids, acylcarnitines, and hexose during the entire experimental period. PCA and PLS-DA analyses showed clearly separated clusters for the two groups on the basis of measured serum metabolites during 5-time points. It is interesting to note that throughout the 17-wk of the study, several serum metabolites [e.g., PC aa C30:0, PC ae C30:1, SM (OH) C24:1, and SM C24:0] appeared to play a consistent role in distinguishing between the CON and metritic cows. For example, concentrations of PC ae C30:1 were consistently 2-fold greater in pre-metritic [i.e., (mean ± SEM, unit: μM): 3.10 ± 0.46 vs 1.32 ± 0.18, P = 0.002 at -8 wks prepartum; 1.91 ± 0.22 vs 0.83 ± 0.10, P = 0.001 at -4 wks prepartum] and metritic (1.89 ± 0.23 vs 0.90 ± 0.11, P = 0.001 at the disease wk) cows compared with CON cows. Furthermore, 5 metabolic pathways (i.e., Lys degradation, biotin metabolism, Trp metabolism, Val – Leu – Ile degradation, and protein biosynthesis) were altered in both premetritic and metritic cows. These new findings give insights into the pathomechanism of metritis in dairy cows. Moreover, the AUCs for five ROC curves were 0.995 (95% CI, 0.945-1) at -8 wks, 0.992 (95% CI, 0.938-1) at -4 wks, 0.988 (95% CI, 0.913-1) at disease wks, 1 (95% CI: 1-1) at +4 wks and 0.99 (95% CI: 1-1) at +8 wks, respectively, which suggest that serum biomarkers identified have pretty accurate predictive, diagnostic, and prognostic abilities for metritis in transition dairy cows.