Febo Elettra, Crisi Paolo Emidio, Oddi Sergio, Pietra Marco, Galiazzo Giorgia, Piscitelli Fabiana, Gramenzi Alessandro, Prinzio Roberta Di, Di Tommaso Morena, Bernabò Nicola, Bisogno Tiziana, Maccarrone Mauro, Boari Andrea
Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
European Center for Brain Research/Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Front Vet Sci. 2021 May 26;8:655311. doi: 10.3389/fvets.2021.655311. eCollection 2021.
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 -arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), -palmitoylethanolamine (PEA), and -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 ( = 0.001) and PEA ( = 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 ( = 0.04), while 2-AG was higher in IRE than in healthy dogs ( = 0.0001). Dogs affected by FRE also showed decreased 2-AG ( = 0.0001) and increased OEA levels ( = 0.0018) compared to IRE dogs. Moreover, dogs with PLE showed increased 2-AG ( = 0.033) and decreased AEA ( = 0.035), OEA ( = 0.016) and PEA ( = 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.
根据对连续试验的治疗反应，犬类慢性肠病（CEs）可分为食物反应性（FRE）、抗生素反应性（ARE）和免疫抑制反应性（IRE）肠病。除了这种分类外，肠道蛋白丢失的犬被归类为蛋白丢失性肠病（PLE）。目前，CEs的诊断耗时、成本高且有时具有侵入性，这也是因为尚未有高灵敏度和特异性的非侵入性生物标志物。因此，本研究旨在评估血浆中循环内源性大麻素水平，作为犬类CEs的潜在诊断标志物。前瞻性纳入了33只出现原发性慢性胃肠道症状并前往意大利泰拉莫和博洛尼亚兽医教学医院就诊的犬，同时纳入30只健康犬作为对照组。在首次就诊时，测量了患有不同CEs的犬以及健康受试者血浆中花生四烯酸乙醇胺（AEA）、2-花生四烯酸甘油酯（2-AG）、棕榈酸乙醇胺（PEA）和油酸乙醇胺（OEA）的水平。与健康犬相比，犬类CEs中2-AG（P = 0.001）和PEA（P = 0.008）的血浆水平升高。特别是，与健康犬相比，FRE组的PEA水平升高（P = 0.04），而IRE组的2-AG水平高于健康犬（P = 0.0001）。与IRE犬相比，受FRE影响的犬还表现出2-AG降低（P = 0.0001）和OEA水平升高（P = 0.0018）。此外，与未出现蛋白丢失的CEs犬相比，PLE犬的2-AG升高（P = 0.033），AEA（P = 0.035）、OEA（P = 0.016）和PEA（P = 0.023）水平降低。在首次就诊时，循环2-AG（0.91；95%置信区间[CI]，0.79 - 1.03）和OEA（0.81；95%CI，0.65 - 0.97）的ROC曲线下面积在区分所研究的不同形式的CEs（FRE、ARE和IRE）方面显示出良好的准确性。本研究表明，犬类CEs中内源性大麻素信号发生改变，并且CE亚型在2-AG、PEA和OEA血浆水平上表现出不同的特征，这表明这些循环生物活性脂质可能有潜力成为犬类CEs的候选生物标志物。
