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

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.

Circulating Endocannabinoids in Canine Multicentric Lymphoma Patients

“…Masoodi et al found that there was no significant relationship between OEA levels and age in their control population or the CLL population; however, it is important to note the majority of their CLL patients were older with 97% being above 50 years and 80% above 60 years old (15). Our results contrast a study on canine chronic enteropathy by Febo et al in which there was no significant association between endocannabinoids and age in healthy dogs (33). This may have been influenced by the age of the control group, the median age of our control group was 84 months as compared to 60 months in their population, however further research evaluating the impact of age is needed.…”

Macronutrient Proportions and Fat Type Impact Ketogenicity and Shape the Circulating Lipidome in Dogs

“…In the current study, the PROT_LoCHO group showed decreased levels of the O-acylglycerol endocannabinoid substrates of the ABDH12 lipase relative to HiCHO, perhaps indicating a role for this food in mitigating adverse effects of obesity on skeletal muscle. The O-acylglycerol endocannabinoid 2-arachidonoylglycerol is increased in circulation of dogs with chronic gastroenteritis relative to healthy dogs [ 95 ] and in the synovial fluid of dogs with osteoarthritis [ 96 ]. In the current study, 2-arachidonoylglycerol decreased following consumption of both LoCHO foods relative to HiCHO, perhaps offering an opportunity for dietary carbohydrate replacement by protein or fat to ameliorate chronic inflammatory conditions in dogs.…”

The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy

“…Palmitic acid was implicated in the pathogenesis of human IBD [46], and its role in intestinal health has been discussed, this fatty acid having been implicated as a ligand of Toll-like receptors (TLR4) [47], whereas down-or upregulation of TLR expressions are found in different canine CE conditions [48,49]. It is also important at this point to consider that membrane phospholipid composition also influences the balance of lipid mediators involved in intestinal diseases; therefore, mediators from palmitic acid, such as palmitoylethanolamide [50,51] and, from PUFA, for example, docosahexanoyl serotonin [52], can be influenced by the change in the precursor's levels in the membrane.…”