Metabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming

Johne’s disease, caused by <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (MAP), causes weight loss, diarrhoea, and reduced milk yields in clinically infected cattle. Asymptomatic, subclinically infected cattle shed MAP bacteria but are frequently not detected by d...

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Autores principales: Emma N. Taylor, Manfred Beckmann, Bernardo Villarreal-Ramos, Hans-Martin Vordermeier, Glyn Hewinson, David Rooke, Luis A. J. Mur, Ad P. Koets
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:124b358003d34bcaab4b0538cc4365202021-11-25T18:20:28ZMetabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming10.3390/metabo111107272218-1989https://doaj.org/article/124b358003d34bcaab4b0538cc4365202021-10-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/727https://doaj.org/toc/2218-1989Johne’s disease, caused by <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (MAP), causes weight loss, diarrhoea, and reduced milk yields in clinically infected cattle. Asymptomatic, subclinically infected cattle shed MAP bacteria but are frequently not detected by diagnostic tests. Herein, we compare the metabolite profiles of sera from subclinically infected Holstein–Friesian heifers and antibody binding to selected MAP antigens. The study used biobanked serum samples from 10 naturally MAP-infected and 10 control heifers, sampled monthly from ~1 to 19 months of age. Sera were assessed using flow infusion electrospray–high-resolution mass spectrometry (FIE–HRMS) on a Q Exactive hybrid quadrupole–Orbitrap mass spectrometer for high-throughput, sensitive, non-targeted metabolite fingerprinting. Partial least-squares discriminant analyses (PLS-DA) and hierarchical cluster analysis (HCA) of the data discriminated between naturally MAP-infected and control heifers. In total, 33 metabolites that differentially accumulated in naturally MAP-infected heifers compared to controls were identified. Five were significantly elevated within MAP-infected heifers throughout the study, i.e., leukotriene B4, bicyclo prostaglandin E2 (bicyclo PGE2), itaconic acid, 2-hydroxyglutaric acid and N6-acetyl-L-lysine. These findings highlight the potential of metabolomics in the identification of novel MAP diagnostic markers and particular biochemical pathways, which may provide insights into the bovine immune response to MAP.Emma N. TaylorManfred BeckmannBernardo Villarreal-RamosHans-Martin VordermeierGlyn HewinsonDavid RookeLuis A. J. MurAd P. KoetsMDPI AGarticle<i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i>metabolomicsantibodyMAP antigenseicosanoidsinflammationMicrobiologyQR1-502ENMetabolites, Vol 11, Iss 727, p 727 (2021)
institution DOAJ
collection DOAJ
language EN
topic <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i>
metabolomics
antibody
MAP antigens
eicosanoids
inflammation
Microbiology
QR1-502
spellingShingle <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i>
metabolomics
antibody
MAP antigens
eicosanoids
inflammation
Microbiology
QR1-502
Emma N. Taylor
Manfred Beckmann
Bernardo Villarreal-Ramos
Hans-Martin Vordermeier
Glyn Hewinson
David Rooke
Luis A. J. Mur
Ad P. Koets
Metabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming
description Johne’s disease, caused by <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (MAP), causes weight loss, diarrhoea, and reduced milk yields in clinically infected cattle. Asymptomatic, subclinically infected cattle shed MAP bacteria but are frequently not detected by diagnostic tests. Herein, we compare the metabolite profiles of sera from subclinically infected Holstein–Friesian heifers and antibody binding to selected MAP antigens. The study used biobanked serum samples from 10 naturally MAP-infected and 10 control heifers, sampled monthly from ~1 to 19 months of age. Sera were assessed using flow infusion electrospray–high-resolution mass spectrometry (FIE–HRMS) on a Q Exactive hybrid quadrupole–Orbitrap mass spectrometer for high-throughput, sensitive, non-targeted metabolite fingerprinting. Partial least-squares discriminant analyses (PLS-DA) and hierarchical cluster analysis (HCA) of the data discriminated between naturally MAP-infected and control heifers. In total, 33 metabolites that differentially accumulated in naturally MAP-infected heifers compared to controls were identified. Five were significantly elevated within MAP-infected heifers throughout the study, i.e., leukotriene B4, bicyclo prostaglandin E2 (bicyclo PGE2), itaconic acid, 2-hydroxyglutaric acid and N6-acetyl-L-lysine. These findings highlight the potential of metabolomics in the identification of novel MAP diagnostic markers and particular biochemical pathways, which may provide insights into the bovine immune response to MAP.
format article
author Emma N. Taylor
Manfred Beckmann
Bernardo Villarreal-Ramos
Hans-Martin Vordermeier
Glyn Hewinson
David Rooke
Luis A. J. Mur
Ad P. Koets
author_facet Emma N. Taylor
Manfred Beckmann
Bernardo Villarreal-Ramos
Hans-Martin Vordermeier
Glyn Hewinson
David Rooke
Luis A. J. Mur
Ad P. Koets
author_sort Emma N. Taylor
title Metabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming
title_short Metabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming
title_full Metabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming
title_fullStr Metabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming
title_full_unstemmed Metabolomic Changes in Naturally MAP-Infected Holstein–Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming
title_sort metabolomic changes in naturally map-infected holstein–friesian heifers indicate immunologically related biochemical reprogramming
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/124b358003d34bcaab4b0538cc436520
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AT bernardovillarrealramos metabolomicchangesinnaturallymapinfectedholsteinfriesianheifersindicateimmunologicallyrelatedbiochemicalreprogramming
AT hansmartinvordermeier metabolomicchangesinnaturallymapinfectedholsteinfriesianheifersindicateimmunologicallyrelatedbiochemicalreprogramming
AT glynhewinson metabolomicchangesinnaturallymapinfectedholsteinfriesianheifersindicateimmunologicallyrelatedbiochemicalreprogramming
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