Milk metabolomic alterations correlated with intramammary infection in dairy cows: From healthy status to clinical mastitis

Mastitis is an udder inflammation and infection causing several economic losses in dairy cows. The milk metabolomic changes associated with clinical or subclinical mastitis have been investigated. However, little is known on milk metabolome associated with intramammary infection. The aim of this study was to investigate the quarter-milk metabolomic profile affected by intramammary infection, subclinical mastitis, and clinical mastitis in dairy cows. A total of 80 quarter-milk samples of multiparous Holstein-Friesian dairy cows were used in this cross-sectional design study. Samples were equally divided into 4 groups: healthy (H; no clinical signs of mastitis, SCC <200,000 cells/mL, negative at bacteriological analysis); intramammary infection (IMI group; no clinical signs of mastitis, SCC <200,000 cells/mL, positive at bacteriological analysis); subclinical mastitis (SCM; no clinical signs of mastitis, SCC ≥200,000 cells/mL, positive at bacteriological analysis); and clinical mastitis (CM; clinical signs of mastitis, SCC ≥200,000 cells/mL, positive at bacteriological analysis). Statistical analysis was conducted by fitting a linear mixed model with the group as the fixed effect, quarter nested within animal as random effect, and DIM as covariate. Analysis identified 45 metabolites, and among them 34 were significantly different among groups. Among these, 18 metabolites (2-aminoadipate, Ala, creatine-phosphate, dimethylamine, N-acetyl-Gly, O-phosphocholine, glucose, lactose, maltose, cis-aconitate, carnitine, fumarate, lactate, phenylacetate, 2-ketobutyrate, acetoacetate, citicoline, and orotate) progressively changed from the H to the CM stage, and other 12 metabolites (Leu, taurine, Val, arabinose, galactose, ribose, acetate, formate, pyruvate, 5-dodecenoic acid, 3-hydroxybutyrate, and ascorbate) differed only in the CM group. These metabolites were related to blood-milk barrier damage, inflammation, oxidative stress, cell proliferation, energy and lipid metabolisms, the citrate (TCA) cycle, systemic energy status, and microorganism metabolism. These results suggest that metabolomic alterations in milk begin to occur when the mammary gland is infected with somatic cells within normal limits and progressively worsen.