Interleukin-13 and interleukin-33 mRNA are underexpressed in the duodenal mucosa of German Shepherd dogs with chronic enteropathy

Background A recent genome‐wide association study in German Shepherd dogs (GSDs) with chronic enteropathy (CE) has identified polymorphisms in the Th2 cytokine genes. Hypothesis/objective To determine if the expression of the Th2 cytokines, interleukin‐13 (IL‐13) and interleukin‐33 (IL‐33), is altered in the duodenal mucosa of GSDs with CE compared to non‐GSDs with CE and healthy dogs. Animals Twenty client‐owned dogs diagnosed with CE (10 GSDs and 10 non‐GSDs) at the Bristol Veterinary School and 8 healthy Beagle dogs from the Iowa State University Service Colony. Methods Retrospective study using archived paraffin‐embedded duodenal biopsy samples. A novel RNA in situ hybridization technology (RNAscope) was used to hybridize IL‐13 and IL‐33 mRNA probes onto at least 10 sections from duodenal biopsy samples for each dog. RNAscope signals were visualized using a microscope and semi‐quantitative assessment was performed by a single operator. Results Based on duodenal villus, subvillus, epithelial, and lamina propria average expression scores, GSDs with CE had significantly lower IL‐13 and IL‐33 mRNA expression compared to non‐GSDs with CE (IL‐13, P \u3c .04; IL‐33, P \u3c .02) and healthy Beagle dogs (IL‐13, P \u3c .02; IL‐33, P \u3c .004). Conclusions and Clinical Importance Similar to human patients with ulcerative colitis, a subtype of human inflammatory bowel disease, these data indicate that Th2 cytokines may be involved in the pathogenesis of CE in GSDs

An undernutrition screening score for dogs with protein‐losing enteropathy: A prospective multicenter study

BACKGROUND: The impact of undernutrition in dogs with protein-losing enteropathy (PLE) caused by inflammatory enteritis, intestinal lymphangiectasia, or both and which variables are most predictive of outcome are unknown. OBJECTIVES: Develop an undernutrition screening score (USS) for use at the time of diagnosis of PLE in dogs, which is predictive of outcome. ANIMALS: Fifty-seven dogs with PLE prospectively recruited from 3 referral hospitals in the United Kingdom. METHODS: An USS based on the presence and severity of 5 variables: appetite, weight loss, and body, muscle, and coat condition and scored out of 15, with higher scores reflecting worse undernutrition, was calculated at the time of diagnosis. Follow-up information was obtained for at least 6 months. RESULTS: Dogs that failed to achieve clinical remission within 6 months had higher USS at diagnosis compared with dogs that achieved remission (median, 7.5; range, 2-14 and median, 5; range, 0-14, respectively). The USS at diagnosis gave an area under the receiver operating characteristic curve (AUC) of 0.656 for predicting nonclinical remission within 6 months, whereas a score consisting of just epaxial muscle loss and coat condition resulted in a larger AUC of 0.728. CONCLUSIONS AND CLINICAL IMPORTANCE: Of the 5 variables assessed in the USS, a combination of epaxial muscle loss and coat condition was most predictive of not achieving clinical remission within 6 months in dogs with PLE. Additional studies will help determine the effect of changes in USS and the 5 associated variables after diagnosis on outcome variables in these dogs

Indoleamine-pyrrole 2,3-dioxygenase-1 (IDO-1) mRNA is over-expressed in the duodenal mucosa and is negatively correlated with serum tryptophan concentrations in dogs with protein-losing enteropathy

Introduction Dogs with protein-losing enteropathy (PLE) have decreased serum tryptophan concentrations, which may contribute to disease pathogenesis. Indoleamine-pyrrole 2,3-dioxygenase-1 (IDO-1) expression is associated with low serum tryptophan concentrations and is increased in the gastrointestinal tract of humans with inflammatory bowel disease (IBD). Therefore, the objective of our study was to determine if the mRNA expression of IDO-1 is increased in the duodenal mucosa of dogs with PLE as compared to dogs with chronic enteropathy (CE) and healthy dogs, and whether this expression is correlated with changes in serum tryptophan concentration. Methods Our study was a retrospective study using archived paraffin-embedded duodenal biopsy specimens from 8 healthy Beagle dogs from the Iowa State University Canine Service Colony and 18 and 6 client-owned dogs diagnosed with CE and PLE, respectively at the Bristol Veterinary School. A novel RNA in situ hybridization (ISH) technology, RNAscope, was used to identify IDO-1 mRNA mucosal expression in duodenal tissues. An IDO-1 specific probe was hybridized onto 10 duodenal biopsy sections from each dog whereby RNAscope signal (mRNA expression) was quantified by a single operator using light microscopy. Results Dogs with PLE had significantly higher mRNA expression of IDO-1 in the duodenal mucosa compared to healthy dogs (mucosal percentage IDO-1 positive: P = 0.0093, (mean ± S.D) control: 19.36 ± 7.08, PLE: 34.12 ± 5.98, average fold difference: 1.76 and mucosal IDO-1 H-score: P = 0.0356, (mean ± S.D) control: 45.26 ± 19.33, PLE: 84.37 ± 19.86, average fold difference: 1.86). The duodenal mucosal mRNA expression of IDO-1 was negatively correlated with serum tryptophan concentrations in dogs with PLE (mucosal IDO-1 H-score: Spearman’s rank correlation coefficient = -0.94, P = 0.0048). Conclusions In conclusion, our study suggests that decreased serum tryptophan concentrations in dogs with PLE is associated with increased intestinal IDO-1 expression. Further studies are needed to determine potential inflammatory pathways responsible for increased expression of IDO-1 in the intestinal tract of dogs with PLE

Fuzapladib in a randomized controlled multicenter masked study in dogs with presumptive acute onset pancreatitis

We read with interest the article by Steiner et al,1 that claims that administration of fuzapladib is safe and effective in reducing 2 clinical scores in dogs with acute pancreatitis (AP). We commend Steiner et al for their efforts in addressing a critical need in veterinary medicine. This letter, however, raises significant concerns regarding the methodology and interpretation of the study results

Polymorphisms in the Tlr4 and Tlr5 Gene Are Significantly Associated with Inflammatory Bowel Disease in German Shepherd Dogs

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease

An investigation into the role of pattern recognition receptors in canine inflammatory bowel disease

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A Preliminary Study of Modulen IBD Liquid Diet in Hospitalized Dogs with Protein-Losing Enteropathy

Modulen IBD is an enteral liquid diet that can induce remission rates similar to glucocorticoids in children with inflammatory bowel disease. The Modulen IBD liquid diet has not been previously investigated in dogs. Our study aimed to describe the use of the Modulen IBD liquid diet in hospitalized dogs with inflammatory protein-losing enteropathy (PLE), including its tolerance and effects on appetite and gastrointestinal signs, and laboratory parameters during hospitalization. Of the 14 dogs hospitalized for PLE that had an esophagostomy feeding tube placed at the time of endoscopy, 5 were eligible and prospectively enrolled. The Modulen IBD liquid diet was supplemented with whey powder isolate and a multivitamin/mineral blend to ensure the diet was complete and balanced for canine adult maintenance and had a macronutrient profile desirable for PLE. All five dogs tolerated tube feedings with the Modulen IBD liquid diet, allowing an increase of 75 to 100% of the resting energy requirement (RER) by day 3 to 4. The diet was administered without glucocorticoid in all five dogs. All five of these dogs had a resolution of anorexia allowing the voluntary intake of a commercial hydrolyzed protein diet prior to the use of glucocorticoids. Of these five dogs, three (60%) had stable or improved serum albumin concentrations (median % increase: 10.3, range: 0–31.1), four (80%) had improved or normalized serum globulin concentrations (median % increase: 12.9, range: 5.1–66.2) and four (80%) had improved or normalized serum cholesterol concentrations (median % increase: 31.5, range: 4.8–63) 2–3 days after initiating the diet. However, there were no significant differences in these selected biochemical parameters pre- and post-feeding with the diet (p > 0.080). In conclusion, the Modulen IBD liquid diet, fed via an esophagostomy feeding tube was well-tolerated in-hospital and resolved anorexia in all dogs and helped to improve selected biochemical parameters in some dogs. Further studies are needed to assess the long-term effects of feeding this diet on the rate of serum albumin increase and remission in dogs with inflammatory PLE

Pre‐illness dietary risk factors in dogs with chronic enteropathy

Abstract Background Dietary factors have been extensively studied as potential triggers of inflammatory bowel disease in humans. Scant literature exists regarding diet as a pre‐illness risk factor in dogs with chronic enteropathy (CE). Hypothesis To evaluate possible pre‐illness dietary risk factors in dogs with CE. Animals Ninety‐five client‐owned dogs; 48 with CE (25 presumptive and 23 confirmed) and 47 without a history of signs of gastrointestinal disease. Methods Retrospective case‐control questionnaire‐based study at a veterinary referral teaching hospital in the United Kingdom. Diet history was obtained relating to the onset of initial presenting signs for all dogs. The main diet consumed underwent ingredient analysis and caloric distribution calculation using a guaranteed analysis convertor software. Length of time the main diet was fed and adherence to the World Small Animal Veterinary Association Global Nutrition Committee guidelines was also recorded. Results The frequency of the main diet containing no carbohydrate was greater for controls (5/47 dogs, 11%) vs the combined presumptive and confirmed CE dogs (0/48 dogs, 0%; P = .05). Fewer dogs with confirmed CE were fed a main diet containing red meat as the primary protein source (2/23 dogs, 9%) vs controls (15/47 dogs, 32%; P = .03). A main diet moisture percentage of ≤14% as fed was significantly associated with confirmed CE in logistic regression analysis (OR 5.71 [95% CI: 1.18‐27.69]; P = .03). Conclusions and Clinical Importance The presence of dietary carbohydrate, protein source, and dietary moisture content, or factors related to moisture content such as preservatives, might play a role as potential pre‐illness dietary risk factors in dogs with CE