Metabolomic changes in lactating multiparous naturally MAP-infected Holstein-Friesian dairy cows suggest changes in mitochondrial energy pathways

• Published in: Research in veterinary science Vol. 152; pp. 354 - 363
• Main Authors: Taylor, E.N., Beckmann, M., Hewinson, G., Rooke, D., Sinclair, L.A., Mur, L.A.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 20-12-2022; Elsevier Limited
• Subjects: Animal lactation; Asymptomatic; Biomarkers; Chronic infection; Correlation analysis; Cow's milk; Dairy cattle; Diarrhea; Fingerprinting; Infections; Lactation; Lactose; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolomics; Milk; Mitochondria; Mycobacterium avium subspecies paratuberculosis; Paratuberculosis; Scientific imaging; Veterinary medicine; Weight loss; United Kingdom > UK; Metabolomics; Mitochondria; Lactose; Mycobacterium avium subspecies paratuberculosis; Lactation; Milk
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2022.09.001

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative organism of Johne's Disease, a chronic intestinal infection of ruminants. Infected cows begin shedding MAP within the asymptomatic, subclinical stage of infection before clinical signs, such as weight loss, diarrhoea and reduced milk yields develop within the clinical stages of disease. Herein, we examine the milk metabolomic profiles of naturally MAP-infected Holstein-Friesian cows. The study used biobanked milk samples which were collected 73.4 ± 3.79 (early lactation) and 143 ± 3.79 (mean ± SE) (mid-lactation) days post-calving from 5 MAP-infected and 5 control multiparous cows. The milk metabolome was assessed using flow infusion electrospray high-resolution mass spectrometry (FIE-HRMS) for sensitive, non-targeted metabolite fingerprinting. Metabolite fingerprinting assessments using partial least squares discriminate analyses (PLS-DA) indicated that lactation stage was a larger source of variation than MAP status. Examining each lactation stage separately for changes associated to MAP-infection status identified 45 metabolites, 33 in early lactation and 12 in mid-lactation, but only 6 metabolites were targeted in both stages of lactation. Pathway enrichment analysis suggested that MAP affected the malate-aspartate shuffle during early lactation. Pearson's correlation analysis indicated relationships between milk lactose concentrations in mid-lactation and 6 metabolites that were tentatively linked to MAP-infection status. The targeted metabolites were suggestive of wider changes in the bioenergetic metabolism that appear to be an acceleration of the effects of progressing lactation in healthy cows. Additionally, milk lactose concentrations suggest that MAP reduces the availability of lactose derivatives.
•Milk samples from MAP-infected dairy cows were collected for metabolomic profiling.•45 metabolites were identified, 33 in early lactation and 12 in mid-lactation.•Pathway analysis highlighted the impact of MAP on the malate-aspartate shuttle.•Correlation analysis suggested links between MAP and reduced lactose concentrations.