Metabotyping reveals distinct metabolic alterations in ketotic cows and identifies early predictive serum biomarkers for the risk of disease

Introduction: Ketosis is a prevalent metabolic disease of transition dairy cows that affects milk yield and the development of other periparturient diseases. Objectives: The objective of this study was to retrospectively metabotype the serum of dairy cows affected by ketosis before clinical signs of disease, during the diagnosis of ketosis, and after the diagnosis of disease and identify potential predictive and diagnostic serum metabolite biomarkers for the risk of ketosis. Methods: Targeted metabolomics was used to identify and quantify 128 serum metabolites in healthy (CON, n = 20) and ketotic (n = 6) cows by DI/LC-MS/MS at −8 and −4 weeks prepartum, during the disease week, and at +4 and +8 weeks after parturition. Results: Significant changes were detected in the levels of several metabolite groups including amino acids, glycerophospholipids, sphingolipids, acylcarnitines, and biogenic amines in the serum of ketotic cows during all time points studied. Conclusions: Results of this study support the idea that ketosis is preceded and associated and followed by alterations in multiple metabolite groups. Moreover, two sets of predictive biomarker models and one set of diagnostic biomarker model with very high sensitivity and specificity were identified. Overall, these findings throw light on the pathobiology of ketosis and some of the metabolites identified might serve as predictive biomarkers for the risk of ketosis. The data must be considered as preliminary given the lower number of ketotic cows in this study and more research with a larger cohort of cows is warranted to validate the results.