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J Proteomics. 2021 Dec 24;254:104452. doi: 10.1016/j.jprot.2021.104452. Epub 2021 Dec 24.

Faecal proteomics in the identification of biomarkers to differentiate canine chronic enteropathies.

Journal of proteomics

Emily L O'Reilly, Anita Horvatić, Josipa Kuleš, Andrea Gelemanović, Vladimir Mrljak, Yixin Huang, Nicola Brady, Christopher C Chadwick, P David Eckersall, Alison Ridyard

Affiliations

  1. Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, Scotland, UK. Electronic address: Emily.O'[email protected].
  2. Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, Zagreb, Croatia; Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10 000 Zagreb, Croatia.
  3. Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10 000 Zagreb, Croatia. Electronic address: [email protected].
  4. Mediterranean Institute for Life Sciences (MedILS), 21000 Split, Croatia.
  5. Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10 000 Zagreb, Croatia. Electronic address: [email protected].
  6. Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, Scotland, UK. Electronic address: [email protected].
  7. Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, Scotland, UK. Electronic address: [email protected].
  8. Life Diagnostics, Inc., 124 Turner Lane, West Chester, PA 19380, USA. Electronic address: [email protected].
  9. Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, Scotland, UK; Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10 000 Zagreb, Croatia. Electronic address: [email protected].
  10. School of Veterinary Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, Scotland, UK. Electronic address: [email protected].

PMID: 34958965 DOI: 10.1016/j.jprot.2021.104452

Abstract

Canine chronic enteropathy (CCE) is a collective term used to describe a group of idiopathic enteropathies of dogs that result in a variety of clinical manifestations of intestinal dysfunction. Clinical stratification into food-responsive enteropathy (FRE) or non-food responsive chronic inflammatory enteropathy (CIE), is made retrospectively based on response to treatments. Faecal extracts from those with a FRE (n = 5) and those with non-food responsive chronic inflammatory enteropathies (CIE) (n = 6) were compared to a healthy control group (n = 14) by applying TMT-based quantitative proteomic approach. Many of the proteins with significant differential abundance between groups were pancreatic or intestinal enzymes with pancreatitis-associated protein (identified as REG3α) and pancreatic M14 metallocarboxypeptidase proteins carboxypeptidase A1 and B identified as being of significantly increased abundance in the CCE group. The reactome analysis revealed the recycling of bile acids and salts and their metabolism to be present in the FRE group, suggesting a possible dysbiotic aetiology. Several acute phase proteins were significantly more abundant in the CCE group with the significant increase in haptoglobin in the CIE group especially notable. Further research of these proteins is needed to fully assess their clinical utility as faecal biomarkers for differentiating CCE cases. SIGNIFICANCE: The identification and characterisation of biomarkers that differentiate FRE from other forms of CIE would prove invaluable in streamlining clinical decision-making and would avoid costly and invasive investigations and delays in implementing effective treatment. Many of the proteins described here, as canine faecal proteins for the first time, have been highlighted in previous human and murine inflammatory bowl disease (IBD) studies initiating a new chapter in canine faecal biomarker research, where early and non-invasive biomarkers for early clinical stratification of CCE cases are needed. Pancreatitis-associated protein, pancreatic M14 metallocarboxypeptidase along with carboxypeptidase A1 and B are identified as being of significantly increased abundance in the CCE groups. Several acute phase proteins, were significantly more abundant in the CCE group notably haptoglobin in dogs with inflammatory enteropathy. The recognition of altered bile acid metabolism in the reactome analysis in the FRE group is significant in CCE which is a complex condition incorporating of immunological, dysbiotic and faecal bile acid dysmetabolism. Both proteomics and immunoassays will enable the characterisation of faecal APPs as well as other inflammatory and immune mediators, and the utilisation of assays, validated for use in analysis of faeces of veterinary species will enable clinical utilisation of faecal matrix to be fully realised.

Copyright © 2022 Elsevier B.V. All rights reserved.

Keywords: CCE; Canine; Diarrhoea; Faecal; Haptoglobin; REG3α

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