Circulating Endocannabinoids as Diagnostic Markers of Canine Chronic Enteropathies: A Pilot Study.

Elettra Febo,Sergio Oddi,Roberta Di Prinzio,Marco Pietra,Fabiana Piscitelli,Paolo Emidio Crisi,Tiziana Bisogno,Mauro Maccarrone,Andrea Boari,Giorgia Galiazzo,Nicola Bernabò,Alessandro Gramenzi,Morena Di Tommaso

doi:10.3389/fvets.2021.655311

Abstract

Chronic enteropathies (CEs) in dogs, according to the treatment response to consecutive trials, are classified as food-responsive (FRE), antibiotic-responsive (ARE), and immunosuppressive-responsive (IRE) enteropathy. In addition to this classification, dogs with loss of protein across the gut are grouped as protein-losing enteropathy (PLE). At present, the diagnosis of CEs is time-consuming, costly and sometimes invasive, also because non-invasive biomarkers with high sensitivity and specificity are not yet available. Therefore, this study aimed at assessing the levels of circulating endocannabinoids in plasma as potential diagnostic markers of canine CEs. Thirty-three dogs with primary chronic gastrointestinal signs presented to Veterinary Teaching Hospitals of Teramo and Bologna (Italy) were prospectively enrolled in the study, and 30 healthy dogs were included as a control group. Plasma levels of N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA) were measured at the time of the first visit in dogs with different CEs, as well as in healthy subjects. Plasma levels of 2-AG (p = 0.001) and PEA (p = 0.008) were increased in canine CEs compared to healthy dogs. In particular, PEA levels were increased in the FRE group compared to healthy dogs (p = 0.04), while 2-AG was higher in IRE than in healthy dogs (p = 0.0001). Dogs affected by FRE also showed decreased 2-AG (p = 0.0001) and increased OEA levels (p = 0.0018) compared to IRE dogs. Moreover, dogs with PLE showed increased 2-AG (p = 0.033) and decreased AEA (p = 0.035), OEA (p = 0.016) and PEA (p = 0.023) levels, when compared to dogs affected by CEs without loss of proteins. The areas under ROC curves for circulating 2-AG (0.91; 95% confidence interval [CI], 0.79–1.03) and OEA (0.81; 95% CI, 0.65–0.97) showed a good accuracy in distinguishing the different forms of CEs under study (FRE, ARE and IRE), at the time of the first visit. The present study demonstrated that endocannabinoid signaling is altered in canine CEs, and that CE subtypes showed distinct profiles of 2-AG, PEA and OEA plasma levels, suggesting that these circulating bioactive lipids might have the potential to become candidate biomarkers for canine CEs.

Highlights

Chronic enteropathies (CEs) in dogs are a group of heterogeneous disorders of undetermined etiologies, characterized by chronic persistent or recurrent gastrointestinal signs and histologic evidence of intestinal mucosal inflammation [1]
According to the guidelines of the International Gastrointestinal Standardization Group, after exclusion of extra-intestinal, infectious or parasitic diseases, CEs can be subdivided retrospectively based on the response to different treatment into: food-responsive enteropathy (FRE), antibioticresponsive enteropathy (ARE) and idiopathic inflammatory bowel disease (IBD)
Histological assessment of inflammation can vary between pathologists, and agreement between pathologists remains poor [3, 4]. In addition to this classification, dogs with loss of protein across the gut are typically grouped as protein-losing enteropathy (PLE), highlighting the more guarded prognosis of this particular form of CE compared to dogs with normal serum albumin concentration [5, 6]

Summary

Introduction

Chronic enteropathies (CEs) in dogs are a group of heterogeneous disorders of undetermined etiologies, characterized by chronic persistent or recurrent gastrointestinal signs and histologic evidence of intestinal mucosal inflammation [1]. Recently the use of the terms immunosuppressant-responsive enteropathy (IRE) or nonresponsive enteropathy (NRE), rather than IBD, has been proposed [1, 2] For the latter, histopathologic evaluation of biopsy specimens is often required to confirm the presence of gut inflammation. Histological assessment of inflammation can vary between pathologists, and agreement between pathologists remains poor [3, 4]. In addition to this classification, dogs with loss of protein across the gut are typically grouped as protein-losing enteropathy (PLE), highlighting the more guarded prognosis of this particular form of CE compared to dogs with normal serum albumin concentration [5, 6]

Objectives

Methods

Results

Conclusion