METABOLOMIC CHANGES IN DAIRY RUMINANTS AFFECTED BY HYPERKETONEMIA

Hyperketonemia is one of the most important health problems in dairy ruminant that negatively affects animals’ health and farm economy. The aims of this PhD research project were 1) to characterize the serum metabolome of healthy and hyperketonemic dairy cows, ewes, and buffaloes; 2) to describe metabolomic differences by performing a comparative analysis within-species between groups (diseased vs non-diseased); 3) to identify the possible consequences of deficiencies and/or excesses of discriminating metabolites in order to improve the prevention and treatment of this disease over time. Forty‑nine Holstein-Friesian dairy cows, forty‑six Sardinian dairy ewes, and sixty-two Mediterranean buffaloes were enrolled for this study. According to the serum concentration of β‑hydroxybutyrate (BHB), animals were divided in three groups for dairy cows (G0, n=12 healthy animals and BHB ≤ 0.50 mmol/L; G1, n=19 healthy animals and 0.51 ≤ BHB < 1.0 mmol/L; G2, n=18 hyperketonemic animals and BHB ≥ 1.0 mmol/L), in two groups for dairy ewes (Non‑HYK, n=28 healthy animals and BHB < 0.80 mmol/L; HYK, n=18 hyperketonemic animals and BHB ≥ 0.80 mmol/L), and in two groups for dairy buffaloes (Group H, n=37 healthy animals and BHB <0.70 mmol/L; Group K, n=25 animals at risk of hyperketonemia and BHB ≥0.70 mmol/L). A total of fifty‑seven metabolites was identified in cows and buffaloes, and fifty-four in ewes with thirteen, fourteen, and twelve metabolites different between groups in cows, ewes, and buffaloes, respectively. The discriminant metabolites of dairy cows were related to the mobilization of body reserves, lipids, amino acid and carbohydrate metabolism, and ruminal fermentation. Changes in metabolites level of dairy ewes indicate altered ruminal microbial populations and fermentations; an interruption of the tricarboxylic acid cycle; initial lack of glucogenic substrates; mobilization of body reserves; the potential alteration of electron transport chain; influence on urea synthesis; alteration of nervous system, inflammatory response, and immune cell function. Differences in metabolites concentration of dairy buffaloes were associated with mobilization of body resources, ruminal fermentations, urea cycle, thyroid hormone synthesis, inflammation, and oxidative stress status. In conclusion, the results indicate: (i) the association between hyperketonemia and euglycemia states, (ii) amino acid deficiency may adversely affect the health status of animals by leading to the establishment or exacerbation of hyperketonemia, (iii) the reduced knowledge about the amino acid requirements in ruminants, (iv) the importance of the inflammatory, immune, and oxidative stress state during hyperketonemia, and (v) the potential effect of this disease on ruminal fermentations.