Metabotypes with elevated protein and lipid catabolism and inflammation precede clinical mastitis in prepartal transition dairy cows

Abstract

Clinical mastitis (CM), the most prevalent and costly disease in dairy cows, is diagnosed most commonly shortly after calving. Current indicators do not satisfactorily predict CM. This study aimed to develop a robust and comprehensive mass spectrometry-based metabolomic and lipidomic workflow using untargeted ultra-performance liquid chromatography high-resolution mass spectrometry for predictive biomarker detection. Using a nested case-control design, we measured weekly during the prepartal transition period differences in serum metabolites, lipids, inflammation markers, and minerals between clinically healthy Holstein dairy cows diagnosed with mastitis postcalving (CMP; n = 8; CM diagnosis d 1 = 3 cows, d 2 = 2 cows, d 4 = 1 cow; d 25 = 1 cow, and d 43 = 1 cow that had subclinical mastitis since d 3) or not (control; n = 9). The largest fold differences between CMP and control cows during the prepartal transition period were observed for 3'-sialyllactose in serum. Seven metabolites (N-methylethanolamine phosphate, choline, phosphorylcholine, free carnitine, trimethyl lysine, tyrosine, and proline) and 3 metabolite groups (carnitines, AA metabolites, and water-soluble phospholipid metabolites) could correctly classify cows for their future CM status at both 21 and 14 d before calving. Biochemical analysis using lipid and metabolite-specific commercial diagnostic kits supported our mass spectrometry-based omics results and additionally showed elevated inflammatory markers (serum amyloid A and visfatin) in CMP cows. In conclusion, metabolic phenotypes (i.e., metabotype) with elevated protein and lipid metabolism and inflammation may precede CM in prepartal transition dairy cows. The discovered serum metabolites and lipids may assist in predictive diagnostics, prevention strategies, and early treatment intervention against CM, and thereby improve cow health and welfare.

Hepatic metabolomics and transcriptomics to study susceptibility to ketosis in response to prepartal nutritional management

“…In general, in terms of metabolite categories, the present metabolomics results are somewhat similar to those reported recently in serum of dairy cows that developed clinical mastitis postpartum [19]. It is also noteworthy that the present data are closely related to blood metabolomics comparisons performed to study non-alcoholic fatty liver disease (NAFLD) [20].…”

Rumen and Serum Metabolomes in Response to Endophyte-Infected Tall Fescue Seed and Isoflavone Supplementation in Beef Steers

“…Therefore, the metabolome of the circulatory system is typically dominated by endogenous metabolites. Because of this systemic nature, metabolites in blood have been used as potential biomarkers to predict feed utilization [17] and production parameters [18], as well as evaluate responses to disease [19,20] and stress [21]. Evaluating the serum metabolome will determine the systemic metabolic response to tall fescue seed and isoflavone supplementation.…”

Acute Phase Proteins (Haptoglobin and Serum Amyloid A) and Pro-Inflammatory Cytokines (IL-12 and IL-10) in Cows Vaccinated with Prototype Killed S. aureus Mastitis Vaccine and Challenged with S. aureus Mastitis Infection.

“…APPs concentration such as SAA and Hp increases during early phase of reaction of cows to bacterial challenge or infection [72,73]. These two APPs aid in determining the progress of inflammatory conditions thereby acting as a valuable diagnostic and prognostic tool in cases of mastitis in dairy cows [74,41].…”

“…APPs are considered a powerful diagnostic measure in field or experimental mastitis studies. The pathogenesis of mastitis have been reported to involve inflammatory reactions [39,40,41] which results into increased production of Acute-Phase Proteins (APP) [31,32]. Recently, APPs are considered as important diagnostic biomarkers not only in veterinary diagnostics but also in human medicine [42,43,44].…”