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. 2022 Mar 23;18(4):21.
doi: 10.1007/s11306-022-01876-w.

Metabolomic changes in Mycobacterium avium subsp. paratuberculosis (MAP) challenged Holstein-Friesian cattle highlight the role of serum amino acids as indicators of immune system activation

Emma N Taylor  1 , Manfred Beckmann  1 , Bryan K Markey  2 , Stephen V Gordon  2 , Glyn Hewinson  3 , David Rooke  4 , Luis A J Mur  5
Affiliations

Metabolomic changes in Mycobacterium avium subsp. paratuberculosis (MAP) challenged Holstein-Friesian cattle highlight the role of serum amino acids as indicators of immune system activation

Emma N Taylor et al. Metabolomics. .

Abstract

Introduction: Paratuberculosis, commonly known as Johne's disease, is a chronic granulomatous infection of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Clinical signs, including reduced milk yields, weight loss and diarrhoea, are typically absent until 2 to 6 years post exposure.

Objectives: To identify metabolomic changes profiles of MAP challenged Holstein-Friesian (HF) cattle and correlate identified metabolites to haematological and immunological parameters.

Methods: At approximately 6 weeks of age, calves (n = 9) were challenged with 3.8 × 109 cells of MAP (clinical isolate CIT003) on 2 consecutive days. Additional unchallenged calves (n = 9) formed the control group. The study used biobanked serum from cattle sampled periodically from 3- to 33-months post challenge. The assessment of sera using flow infusion electrospray high resolution mass spectrometry (FIE-HRMS) for high throughput, sensitive, non-targeted metabolite fingerprinting highlighted differences in metabolite levels between the two groups.

Results: In total, 25 metabolites which were differentially accumulated in MAP challenged cattle were identified, including 20 which displayed correlation to haematology parameters, particularly monocyte levels.

Conclusion: The targeted metabolites suggest shifts in amino acid metabolism that could reflect immune system activation linked to MAP and as well as differences in phosphocholine levels which could reflect activation of the Th1 (tending towards pro-inflammatory) immune response. If verified by future work, selected metabolites could be used as biomarkers to diagnose and manage MAP infected cattle.

Keywords: Amino acids; Haematology; Immune response; Metabolomics; Mycobacterium avium subspecies paratuberculosis.

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Conflict of interest statement

Emma N. Taylor, Manfred Beckmann, Bryan K. Markey, Stephen V. Gordon, Glyn Hewinson, David Rooke, Luis A. J. Mur declares that he has no conflict of interest.

Figures

Fig. 1
Fig. 1
Partial least-squares discriminant analysis (PLS-DA) for MAP challenged and control cattle in the a negative ionization and b positive ionization modes 24-months post MAP-challenge. The light red and green ellipses represent 95% confidence intervals
Fig. 2
Fig. 2
Major metabolite changes differentiating between MAP challenged and control cattle between ∼ 3-month and 33-months post MAP inoculation, Metabolites detected in a negative and b positive ionization modes
Fig. 3
Fig. 3
Significant metabolite changes (negative ionization model) differentiating between MAP challenge status and interferon-y release assay IDEXX criteria MAP interpretation results between 24 and 28-months post MAP challenge
Fig. 4
Fig. 4
Relationship between monocytes content (%) and a 2-oxosuccinamate and maleylacetoacetic acid as well as b glyoxylic acid and ureidoglycolic 33-months post MAP challenge
Fig. 5
Fig. 5
Box and whisker plots of metabolites which display reduced overlapping between groups, MAP challenged and control cattle, from 21 months post MAP challenge. Blue boxplpots = MAP challenged cattle, green boxplots = control cattle (Color figure online)
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