Heterogeneity of mesenchymal stem cells as a limiting factor in their clinical application to inflammatory bowel disease in dogs and cats.

Inflammatory bowel disease (IBD) is a major subtype of chronic enteropathies in dogs and cats. Conventional drugs such as immunomodulatory medicines as glucocorticoids and/or other anti-inflammatory are mainly applied for treatment. However, these drugs are not always effective to maintain remission from IBD and are limited by unacceptable side effects. Hence, more effective and safe therapeutic options need to be developed. Mesenchymal stem cells (MSCs) are multipotent stem cells with a self-renewal capacity, and have immunomodulatory, anti-inflammatory, anti-fibrotic, and tissue repair properties. Therefore, the application of MSCs as an alternative therapy for IBD has great potential in veterinary medicine. The efficacy of adipose tissue-derived MSC (ADSC) therapy for IBD in dogs and cats has been reported, including numerous studies in animal models. However, treatment outcomes in clinical trials of human IBD patients have not been consistent with preclinical studies. MSC-based therapy for various diseases has received widespread attention, but various problems in such therapy remain, among which no consensus has been reached on the preparation and treatment procedures for MSCs, and cellular heterogeneity of MSCs may be an issue. This review describes the current status of ADSC therapy for canine and feline IBD and summarizes the cellular heterogeneity of canine ADSCs, to highlight the necessity for further reduction or elimination of MSCs heterogeneity and standardization of MSC-based therapies.

Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

OBJECTIVES: Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. MATERIALS AND METHODS: Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. RESULTS: Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. CLINICAL SIGNIFICANCE: Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

A RETROSPECTIVE STUDY OF DISEASE PROCESSES IN MANED WOLVES (CHRYSOCYON BRACHYURUS) IN NORTH AMERICAN ZOOLOGICAL INSTITUTIONS WITH EMPHASIS ON UROLITHIASIS, INFLAMMATORY BOWEL DISEASE, AND NEOPLASIA.

The objective of this retrospective study is to summarize causes of disease and mortality in maned wolves (Chrysocyon brachyurus) in the North American Species Survival Plan Program (SSP) population. This information will inform and enhance animal health, husbandry, and conservation efforts. Pathology reports were requested from all zoological institutions housing maned wolves between 1930 and 2021. Data were reviewed and cause of death (COD) and reported diseases were summarized and compared by age group, organ system and disease process. One hundred and seventy-one wolves, 82 females and 89 males, met the inclusion criteria. The majority were geriatric (>11 yr; n = 96) or adult (2-11 yr; n = 67). Noninfectious diseases were the most common COD by process (n = 94; 54.9%). For COD by organ system, diseases of the digestive (n = 41) and urinary (n = 34) systems were most common. Neoplasia was the most common noninfectious COD and was the primary COD in 37 wolves (21.6% overall; 39.4% of noninfectious diseases). A total of 145 benign (n = 72) and malignant (n = 73) neoplasms were diagnosed in 44 individuals. Dysgerminoma was the most commonly reported tumor (n = 18), and was the most common neoplastic COD (n = 8). Cystinuria or urolithiasis (n = 71) and gastritis, enteritis, enterocolitis, or colitis (n = 50) (overall and grouped in each system due to presumed common underlying cause) were also common but were more often reported as comorbidities than as COD (n = 16 and n = 11, respectively). Infectious COD were reported in 17 wolves and included babesiosis (n = 4), acanthocephalans (n = 2), and one viral infection. Infections with a variety of bacteria in different organ systems were a COD in eight wolves.

Traces of Canine Inflammatory Bowel Disease Reflected by Intestinal Organoids.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects humans and several domestic animal species, including cats and dogs. In this study, we have analyzed duodenal organoids derived from canine IBD patients using quantitative proteomics. Our objective was to investigate whether these organoids show phenotypic traits of the disease compared with control organoids obtained from healthy donors. To this aim, IBD and control organoids were subjected to quantitative proteomics analysis via liquid chromatography-mass spectrometry. The obtained data revealed notable differences between the two groups. The IBD organoids exhibited several alterations at the levels of multiple proteins that are consistent with some known IBD alterations. The observed phenotype in the IBD organoids to some degree mirrors the corresponding intestinal condition, rendering them a compelling approach for investigating the disease and advancing drug exploration. Additionally, our study revealed similarities to some human IBD biomarkers, further emphasizing the translational and comparative value of dogs for future investigations related to the causes and treatment of IBD. Relevant proteins such as CALU, FLNA, MSN and HMGA2, which are related to intestinal diseases, were all upregulated in the IBD duodenal organoids. At the same time, other proteins such as intestinal keratins and the mucosal immunity PIGR were depleted in these IBD organoids. Based on these findings, we propose that these organoids could serve as a valuable tool for evaluating the efficacy of therapeutic interventions against canine IBD.

Application of automated machine learning for histological evaluation of feline endoscopic samples.

Differentiating intestinal T-cell lymphoma from chronic enteropathy (CE) in endoscopic samples is often challenging. In the present study, automated machine learning systems were developed to distinguish between the two diseases, predict clonality, and detect prognostic factors of intestinal lymphoma in cats. Four models were created for four experimental conditions: experiment 1 to distinguish between intestinal T-cell lymphoma and CE; experiment 2 to distinguish large cell lymphoma, small cell lymphoma, and CE; experiment 3 to distinguish granzyme B+ lymphoma, granzyme B- lymphoma, and CE; and experiment 4 to distinguish between T-cell receptor (TCR) clonal population and TCR polyclonal population. After each experiment, a pathologist reviewed the test images and scored for lymphocytic infiltration, epitheliotropism, and epithelial injury. The models of experiments 1-4 achieved area under the receiver operating characteristic curve scores of 0.943 (precision, 87.59%; recall, 87.59%), 0.962 (precision, 86.30%; recall, 86.30%), 0.904 (precision, 82.86%; recall, 80%), and 0.904 (precision, 81.25%; recall, 81.25%), respectively. The images predicted as intestinal T-cell lymphoma showed significant infiltration of lymphocytes and epitheliotropism than CE. These models can provide evaluation tools to assist pathologists with differentiating between intestinal T-cell lymphoma and CE.

Faecal microbiota and fatty acids in feline chronic enteropathy.

BACKGROUND: Feline chronic enteropathy is a set of disorders defined as the presence of clinical signs of gastrointestinal disease for at least three weeks. The most common final diagnoses are inflammatory bowel disease and alimentary small cell lymphoma. The etiopathogenesis of these diseases is incompletely understood; however, it is hypothesised that they involve a combination of factors, including altered composition and/or functionality of the intestinal microbiome. An important factor in the interplay of the microbiome and host is the production of short- and branched-chain fatty acids.  The aim of this study was to evaluate the possible differences in faecal microbiota diversity, composition and fatty acid production between cats suffering from chronic enteropathy and healthy cats. Sixteen cats suffering from chronic enteropathy and fourteen healthy control cats were enrolled in the study. The microbiota compositions of faecal samples were analysed by using next-generation amplicon sequencing of the V3V4 fragment of the 16S rRNA gene. Fatty acids were evaluated by high-performance liquid chromatography. RESULTS: Both the alpha and beta diversities were significantly lower in samples obtained from cats with chronic enteropathy. The relative abundance of the phylum Proteobacteria, orders Lactobacillales and Enterobacterales, family Enteriobacteriaceae and genus Escherichia Shigella were higher in diseased cats, whereas the abundance of the phylum Bacteroidota and order Peptococcales were higher in control cats. The faecal concentrations of short-chain fatty acids were higher in cats with chronic enteropathy, with lower propionate proportions and higher butyrate proportions. CONCLUSION: The study revealed alterations in microbiota compositions and short-chain fatty acid concentration in cats suffering from chronic enteropathy, which is an important finding both for research on the pathogenesis of the disease and for potential therapeutic interventions in the form of faecal microbiota transplantation and/or probiotic supplementation.

Validation of the fCAL turbo immunoturbidimetric assay for measurement of calprotectin in porcine and bovine fecal samples.

The concentration of calprotectin in feces is a well-studied marker of gastrointestinal inflammation in humans. However, little is known about fecal calprotectin in farm animals. In this work, we have validated an immunoturbidimetric method for fecal calprotectin (Bühlmann fCAL® turbo assay, Schönenbuch, Switzerland) in porcine and bovine fecal samples. Linearity was evaluated by serial dilution (R2 > 0.97 was obtained for both species). Accuracy was assessed by a recovery study, with results between 80 and 120% for low, medium, and high samples in both species. Intra- and inter-assay variability was <20%. Limit of detection was 6.4 µg/g in pig and 5.3 µg/g in cow. Limit of quantification was 13.4 µg/g (pig) and 11.1 µg/g (cow). Additionally, clinical validation has been included to evaluate the ability of the assay to detect inflammatory status in the intestine under different management conditions. In experiments with porcine, it was found that piglets treated with ZnO had lower concentrations of fecal calprotectin. In a second experiment in bovine, calves with diarrhea had higher concentration of fecal calprotectin. The Bühlmann fCAL® turbo assay is suitable for measurement of calprotectin in porcine and bovine fecal samples. Moreover, fecal calprotectin could be a good biomarker of intestinal inflammation in both species.

Randomized controlled trial of hydrolyzed fish diets in dogs with chronic enteropathy.

BACKGROUND: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. OBJECTIVES: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non-PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. ANIMALS: Thirty-one client-owned dogs with CE: 23 non-PLE, 8 PLE. METHODS: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long-term follow-up at 26 weeks. Concurrent medications were allowed in PLE. RESULTS: Nineteen of 23 (83%; 95% confidence interval [CI], 60%-94%) non-PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%-100%) at 26 weeks. Serum cobalamin concentration was increased (P < .05) and maintained by diet. Serum folate concentration decreased posttreatment (P < .05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P < .05) in dogs with PLE. CONCLUSIONS AND CLINICAL IMPORTANCE: Changing diet, independent of antigen restriction or supplemental ingredients, induced long-term remission in dogs with non-PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE.

Efficacy of an elemental diet in achieving clinical remission in dogs with chronic enteropathy.

BACKGROUND: Diet may induce clinical remission in dogs with chronic enteropathy (CE). Elemental diets (EDs), providing protein as amino acids, modulate intestinal immunity and microbiome in rodents and humans. HYPOTHESIS: Evaluate the impact of an amino acid-based kibble (EL) on CE clinical activity and gastrointestinal (GI)-relevant variables. ANIMALS: Client-owned dogs (n = 23) with inadequately controlled CE. METHODS: Prospective, uncontrolled clinical trial. Diagnostic evaluation including upper and lower GI endoscopy was performed before study entry. Canine chronic enteropathy clinical activity index (CCECAI), serum biomarkers, and fecal microbiome were evaluated before and after 2 weeks of EL. Dogs with stable or improved CE remained in the study for another 6 weeks. Pre- and post-EL clinical and microbiological variables were compared statistically using a mixed model. RESULTS: After 2 weeks of EL, 15 of 22 dogs (68%; 95% confidence interval [CI], 47%-84%) consuming the diet were classified as responders with a median (range) decrease in CCECAI from 6 (3-12) to 2 (0-9; P < .001). Fourteen of 15 responders and 2/7 nonresponders at 2 weeks completed the trial; all 16 were experiencing adequate control at week 8 with a median CCECAI of 2 (0-3). In total, 16/23 dogs (70%; 95% CI, 49%-84%) were responders. Feeding EL caused shifts in fecal bacterial communities, which differed between responders and nonresponders. Serum biomarker concentrations were unchanged throughout the study apart from serum alkaline phosphatase activity. CONCLUSIONS: Exclusive feeding of EL improved clinical signs in 16 of 23 dogs with uncontrolled CE. Fecal microbiome shifts were associated with response to diet and may represent a mechanism for clinical improvement.

Pre-illness dietary risk factors in dogs with chronic enteropathy.

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.

Histopathologic diagnosis and patient characteristics in cats with small intestinal obstructions secondary to trichobezoars.

OBJECTIVES: The aim of the present study was to describe the distribution of gastrointestinal histopathology findings associated with gastrointestinal obstructions secondary to trichobezoar formation in cats. METHODS: A total of 100 surgical gastrointestinal biopsies were obtained from 44 cats with gastrointestinal obstructions secondary to a trichobezoar. Medical records, including signalment, type and duration of clinical signs, surgical reports and histopathologic analysis, were reviewed for each cat. RESULTS: Biopsies taken near the site of the trichobezoar were more likely to show neutrophilic inflammation and mucosal erosion/ulceration compared with biopsies taken elsewhere in the small intestine. Lymphoplasmacytic and mixed lymphocytic and eosinophilic populations were the most common histopathologic findings from all biopsies followed by alimentary small cell lymphoma. Biopsy samples were more likely to represent a diagnosis of alimentary lymphoma in cats older than 10 years. CONCLUSIONS AND RELEVANCE: Gastrointestinal biopsies taken at the time of surgery in cats with trichobezoar obstructions may represent an important diagnostic tool for further evaluation of potential feline chronic enteropathy. Biopsies taken at the site of the obstruction should be interpreted cautiously as the presence of a trichobezoar may induce an acute inflammatory reaction. The resultant histologic interpretation at this site may not represent the chronic state of the intestinal mucosa, supporting the utility of obtaining multiple biopsies orad and aborad to the obstruction.

Combining ultrasound radiomics, complete blood count, and serum biochemical biomarkers for diagnosing intestinal disorders in cats using machine learning.

This retrospective analytical observational cohort study aimed to model and predict the classification of feline intestinal diseases from segmentations of a transverse section from small intestine ultrasound (US) image, complete blood count (CBC), and serum biochemical profile data using a variety of machine-learning approaches. In 149 cats from three institutions, images were obtained from cats with biopsy-confirmed small cell epitheliotropic lymphoma (lymphoma), inflammatory bowel disease (IBD), no pathology ("healthy"), and other conditions (warrant a biopsy for further diagnosis). CBC, blood serum chemistry, small intestinal ultrasound, and small intestinal biopsy were obtained within a 2-week interval. CBC and serum biomarkers and radiomic features were combined for modeling. Four classification schemes were investigated: (1) normal versus abnormal; (2) warranting or not warranting a biopsy; (3) lymphoma, IBD, healthy, or other conditions; and (4) lymphoma, IBD, or other conditions. Two feature selection methods were used to identify the top 3, 5, 10, and 20 features, and six machine learning models were trained. The average (95% CI) performance of models for all combinations of features, numbers of features, and types of classifiers was 0.886 (0.871-0.912) for Model 1 (normal vs. abnormal), 0.751 (0.735-0.818) for Model 2 (biopsy vs. no biopsy), 0.504 (0.450-0.556) for Model 3 (lymphoma, IBD, healthy, or other), and 0.531 (0.426-0.589), for Model 4 (lymphoma, IBD, or other). Our findings suggest model accuracies above 0.85 can be achieved in Model 1 and 2, and that including CBC and biochemistry data with US radiomics data did not significantly improve accuracy in our models.

Fecal acute phase proteins in cats with chronic enteropathies.

BACKGROUND: Chronic enteropathies (CE) are common in cats and reliable biomarkers that can distinguish different causes and predict or monitor response to treatment are currently lacking. HYPOTHESIS: To evaluate certain acute phase proteins in feces that could potentially be used as biomarkers in cats with CE. ANIMALS: Twenty-eight cats with either inflammatory bowel disease (IBD; n = 13), food-responsive enteropathy (FRE; n = 3) or small cell gastrointestinal lymphoma (SCGL; n = 12) and 29 healthy control cats were prospectively enrolled. METHODS: Fecal concentrations of haptoglobin, alpha-1-acid-glycoprotein (AGP), pancreatitis-associated protein-1 (PAP-1), ceruloplasmin, and C-reactive protein (CRP) were measured using Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL) immunoassays before and after initiation of treatment. Cats were treated with diet and/or prednisolone (IBD cats), plus chlorambucil (SCGL cats). RESULTS: Compared with controls, median fecal AGP concentrations were significantly lower (25.1 vs 1.8 µg/g; P = .003) and median fecal haptoglobin (0.17 vs 0.5 µg/g), PAP-1 (0.04 vs 0.4 µg/g) and ceruloplasmin (0.15 vs 4.2 µg/g) concentrations were significantly higher (P < .001) in cats with CE. Median fecal AGP concentrations were significantly lower (P = .01) in cats with IBD and FRE (0.6 µg/g) compared with cats with SCGL (10.75 µg/g). A significant reduction was found in CE cats after treatment for median fecal ceruloplasmin concentrations (6.36 vs 1.16 µg/g; P = .04). CONCLUSIONS: Fecal AGP concentration shows promise to differentiate cats with SCGL from cats with IBD and FRE. Fecal ceruloplasmin concentrations may be useful to objectively monitor response to treatment in cats with CE.

Serum proteome profiles in cats with chronic enteropathies.

BACKGROUND: Serum protein biomarkers are used to diagnose, monitor treatment response, and to differentiate various forms of chronic enteropathies (CE) in humans. The utility of liquid biopsy proteomic approaches has not been examined in cats. HYPOTHESIS/OBJECTIVES: To explore the serum proteome in cats to identify markers differentiating healthy cats from cats with CE. ANIMALS: Ten cats with CE with signs of gastrointestinal disease of at least 3 weeks duration, and biopsy-confirmed diagnoses, with or without treatment and 19 healthy cats were included. METHODS: Cross-sectional, multicenter, exploratory study with cases recruited from 3 veterinary hospitals between May 2019 and November 2020. Serum samples were analyzed and evaluated using mass spectrometry-based proteomic techniques. RESULTS: Twenty-six proteins were significantly (P < .02, ≥5-fold change in abundance) differentially expressed between cats with CE and controls. Thrombospondin-1 (THBS1) was identified with >50-fold increase in abundance in cats with CE (P < 0.001) compared to healthy cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Damage to the gut lining released marker proteins of chronic inflammation that were detectable in serum samples of cats. This early-stage exploratory study strongly supports THBS1 as a candidate biomarker for chronic inflammatory enteropathy in cats.

Characterization of canine intestinal microRNA expression in inflammatory bowel disease and T-cell lymphoma.

Differentiating between canine inflammatory bowel disease (IBD) and intestinal T-cell lymphoma by histopathological examination of endoscopically-derived intestinal biopsies can be challenging and involves an invasive procedure requiring specialized equipment and training. A rapid, non-invasive method of diagnosis, such as blood or faecal analysis for a conserved and stable biomarker, would be a useful adjunct or replacement. Studies on dogs and humans with various types of lymphoma have shown altered microRNA (miRNA) expression patterns in blood, faeces and tissues indicating their potential use as biomarkers of disease. The present study used residual archived endoscopically-derived, formalin-fixed, paraffin-embedded (FFPE) duodenal tissue taken from pet dogs undergoing routine investigation of gastrointestinal disease. The dogs had previously been diagnosed with either normal/minimal intestinal inflammation, severe IBD or intestinal T-cell lymphoma. Next generation sequencing with qPCR validation was used to elucidate differentially expressed miRNAs between groups. Our results show that miRNA can be extracted from archived endoscopically-derived FFPE tissues from the canine duodenum and used to differentiate normal/minimally inflamed canine duodenal tissue from severe lymphoplasmacytic IBD and T-cell lymphoma.

ACVIM consensus statement guidelines on diagnosing and distinguishing low-grade neoplastic from inflammatory lymphocytic chronic enteropathies in cats.

BACKGROUND: Lymphoplasmacytic enteritis (LPE) and low-grade intestinal T cell lymphoma (LGITL) are common diseases in older cats, but their diagnosis and differentiation remain challenging. OBJECTIVES: To summarize the current literature on etiopathogenesis and diagnosis of LPE and LGITL in cats and provide guidance on the differentiation between LPE and LGITL in cats. To provide statements established using evidence-based approaches or where such evidence is lacking, statements based on consensus of experts in the field. ANIMALS: None. METHODS: A panel of 6 experts in the field (2 internists, 1 radiologist, 1 anatomic pathologist, 1 clonality expert, 1 oncologist) with the support of a human medical immunologist, was formed to assess and summarize evidence in the peer-reviewed literature and complement it with consensus recommendations. RESULTS: Despite increasing interest on the topic for clinicians and pathologists, few prospective studies were available, and interpretation of the pertinent literature often was challenging because of the heterogeneity of the cases. Most recommendations by the panel were supported by a moderate or low level of evidence. Several understudied areas were identified, including cellular markers using immunohistochemistry, genomics, and transcriptomic studies. CONCLUSIONS AND CLINICAL IMPORTANCE: To date, no single diagnostic criterion or known biomarker reliably differentiates inflammatory lesions from neoplastic lymphoproliferations in the intestinal tract of cats and a diagnosis currently is established by integrating all available clinical and diagnostic data. Histopathology remains the mainstay to better differentiate LPE from LGITL in cats with chronic enteropathy.

Prognostic value of increased intraepithelial lymphocytes and lymphocytic clonality in dogs with chronic enteropathy or small-cell lymphoma.

The clinical significance of severe infiltration of small intraepithelial lymphocytes (IEL) and the results of polymerase chain reaction for antigen receptor rearrangement (PARR) in dogs with chronic enteropathy (CE) and small-cell lymphoma (SCL) are controversial. This cohort study aimed to evaluate the prognostic significance of the IEL and PARR results in dogs with CE or SCL. Although definitive diagnostic histopathological criteria for SCL in dogs have yet to be established, dogs with the histopathological findings of severe IEL infiltration were diagnosed with SCL in this study. One hundred and nineteen dogs were recruited, with 23 dogs classified as having SCL and 96 dogs as having CE. The positive rate of PARR was 59.6 % (71/119) in the duodenum and 57.7 % (64/111) in the ileum. Subsequently, three dogs with SCL and four dogs with CE developed large-cell lymphoma (LCL). The median overall survival (OS) of dogs with SCL was 700 days (range, 6-1410 days), and that of dogs with CE was not reached. In the log-rank test, shorter OS was observed in cases with histopathological SCL (P = 0.035), clonal TCRγ rearrangement in the duodenum (P = 0.012), and clonal IgH rearrangement in the ileum (P < 0.0001). The Cox proportional hazards model adjusted for sex and age showed that histopathological SCL (hazard ratio [HR] 1.74; 95 % confidence interval [CI], 0.83-3.65), duodenal clonal TCRγ rearrangement (HR, 1.80; 95 % CI, 0.86-3.75), and ileal clonal IgH rearrangement (HR, 2.28; 95 % CI, 0.92-5.70) could shorten overall survival, although their 95 % CIs included 1.0. These results indicate that severe IEL infiltration could be a useful histopathological feature for diagnosing SCL, and clonality-positive results could be a negative prognostic factor in dogs with CE. Furthermore, the development of LCL should be carefully monitored in dogs with CE and SCL..

Serum proteome of dogs with chronic enteropathy.

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.

Faecal microbiome transplantation improves clinical signs of chronic idiopathic large bowel diarrhoea in working dogs.

BACKGROUND: Chronic diarrhoea is a common clinical sign in dogs with chronic enteropathy, and psyllium husk has been shown to improve clinical signs in affected dogs. The aim of this study was to investigate whether faecal microbiome transplant has a similar effect in alleviating clinical signs in dogs with chronic large bowel diarrhoea. METHOD: Thirty large-breed working dogs with chronic large bowel diarrhoea were divided into a psyllium group (PG) and a faecal microbiome transplant group (FMTG). To the PG, 16 g/day of psyllium husk was administered for 30 days. The FMTG received faecal microbiome transplantation (FMT) once via enema. A daily log of faecal characteristics was kept, and the dogs' canine inflammatory bowel disease index (CIBDAI) and body condition scores (BCS) were determined. A Wilcoxon-Mann-Whitney test was used to compare group results. In addition, the Kaplan-Meier test was used to evaluate the occurrence rate of 1 day or more of diarrhoea and 2 days or more of diarrhoea by day 30. RESULTS: The sample had a mean age of 3.9 ± 2.1 years and a bodyweight of 25.3 ± 6.8 kg. The FMTG showed a more rapid onset of CIBDAI improvement but no difference in other measures. At 30 days, the FMTG showed a greater improvement in bodyweight and BCS, but no differences were observed in faecal scores, defaecation frequency and time of appearance of episodes of diarrhoea. Time played a significant positive role in the results observed across both groups (p < 0.05). LIMITATIONS: This study did not compare the microbiomes of the dogs before and after treatment, so the role of specific types of bacteria cannot be determined. CONCLUSION: Psyllium husk and FMT had similar effects in improving clinical signs of chronic large bowel diarrhoea.

Characterization of intestinal fibrosis in cats with chronic inflammatory enteropathy.

BACKGROUND: Intestinal fibrosis (IF) is commonly identified on histopathology of intestinal biopsy specimens (IBSp) from cats with chronic inflammatory enteropathy (CIE) however, its clinical relevance is unknown. OBJECTIVES: Characterize and determine the clinical relevance of IF in cats with CIE. ANIMALS: Sixty-five client-owned cats diagnosed with CIE after gastrointestinal histopathology from a single referral hospital in the United Kingdom. METHODS: Medical records were retrospectively searched for cases of CIE on the basis of histopathology of IBSp. The IBSp from eligible cats were re-reviewed by a single board-certified veterinary pathologist for inclusion. Masson's trichrome (MT) stain and immunohistochemical labeling using antivimentin and anticollagen I antibodies to identify IF. For each case, various variables at the time of diagnostic investigation were recorded and referring veterinarians were contacted for follow-up information. RESULTS: Mucosal fibrosis was identified in 51% of duodenal and 76% of colonic hematoxylin and eosin (HE)-stained IBSp. Vimentin labeling and MT staining identified additional cases of IF in 65% and 58% of the duodenal biopsy specimens, respectively. Vimentin labeling detected IF in 79% of the colonic biopsy specimens. Positive vimentin labeling and MT staining of the colonic mucosa were associated with decreased likelihood of attaining clinical remission and increased risk of death because of CIE (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Additional stains at initial histopathologic examination of IBSp allow for better identification of IF compared to routine HE staining. Identification of IF in colonic biopsy specimens by vimentin immunolabeling and MT staining may provide prognostic information in cats with CIE.