Serum proteome of dogs with chronic enteropathy

Abstract

Background: Chronic enteropathy (CE) is common in dogs and can occur with multiple etiologies including food-responsive enteropathy (FRE) and idiopathic inflammatory bowel disease (IBD).

Hypothesis/objective: To study the protein profile and pathway differences among dogs with FRE, IBD, and healthy controls using serum proteome analysis.

Animals: Nine CE dogs with signs of gastrointestinal disease and histologically confirmed chronic inflammatory enteropathy and 16 healthy controls.

Methods: A cross-sectional study with cases recruited from 2 veterinary hospitals between May 2019 and November 2020 was performed. Serum samples were analyzed using mass spectrometry-based proteomic techniques.

Results: Proteomic profiles showed marked variation in relative protein abundances. Forty-five proteins were significantly (P ≤ .01) differentially expressed among the dogs with CE and controls with ≥2-fold change in abundance. The fold change of dogs with IBD normalized to controls was more pronounced for the majority of proteins than that seen in the dogs with FRE normalized to control dogs. Proteins involving reactive oxygen species, cytokine activation, acute phase response signaling, and lipid metabolism were altered in dogs with CE.

Conclusions and clinical importance: Cytokine alterations, acute phase response signaling, and lipid metabolism are likely involved in pathogenesis of CE. Although there are insufficient current data to justify the use of proteomic biomarkers for assessment of CE in dogs, our study identifies potential candidates.

Keywords: biomarkers; food-responsive enteropathy; inflammatory bowel disease; proteins; proteomics.

FIGURE 1

(A) Molecular functions of ≥2‐fold increased protein in abundance and significance in dogs with chronic enteropathy (CE) compared to controls. (B) Biological processes of ≥2‐fold increased protein in abundance and significance in dogs with CE compared to controls. (C) Protein classes of ≥2‐fold increased protein in abundance and significance in dogs with CE compared to controls.

FIGURE 2

(A) Summary figure of the enriched canonical pathways. Activated pathways are illustrated by orange color, inhibited pathways are illustrated by blue color. Cytokine IL6 activates release of IFNγ (labeled as IFNG on diagram) is a key instigator of inflammatory processes. IFNγ also activates MAPK3 leading to further activation of nitric oxide and reactive oxygen species (ROS) production. Orange shows increased abundance of identified proteins. (B) The lipid metabolism pathway with protein interactions. Increased apolipoproteins, activation (orange) of peroxisome proliferator activator receptor (Ppar) and cholesterol efflux are related to ROS and inflammation leading to inhibition (blue) of proinflammatory cytokines and NAD energy metabolism. Stat3 also leads to activation (orange) of chains of fibrinogen (FGB, FGG) which in turn activates fibrin and then plasminogen (PLG) and ceruloplasmin (CP). Green shows reduced abundance and orange shows increased abundance of identified proteins. Other colors (pink) indicate intermediate abundance.