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Chronic enteropathies (CE) are common disorders in cats and the differentiation between the two main underlying diseases, inflammatory bowel disease (IBD) and low-grade intestinal T-cell lymphoma (LGITL), can be challenging. Characterization of the serum metabolome could provide further information on alterations of disease-associated metabolic pathways and may identify diagnostic or therapeutic targets. Unbiased metabolomics analysis of serum from 28 cats with CE (14 cats with IBD, 14 cats with LGITL) and 14 healthy controls identified 1,007 named metabolites, of which 129 were significantly different in cats with CE compared to healthy controls at baseline. Random Forest analysis revealed a predictive accuracy of 90% for differentiating controls from cats with chronic enteropathy. Metabolic pathways found to be significantly altered included phospholipids, amino acids, thiamine, and tryptophan metabolism. Several metabolites were found to be significantly different between cats with IBD versus LGITL, including several sphingolipids, phosphatidylcholine 40:7, uridine, pinitol, 3,4-dihydroxybenzoic acid, and glucuronic acid. However, random forest analysis revealed a poor group predictive accuracy of 60% for the differentiation of IBD from LGITL. Of 129 compounds found to be significantly different between healthy cats and cats with CE at baseline, 58 remained different following treatment.

We are grateful to the authors for providing additional data to demonstrate the presence of domestic cat hepadnavirus in lymphoma tissues [...].

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Chronic enteropathy (CE) in cats encompasses food-responsive enteropathy, chronic inflammatory enteropathy (or inflammatory bowel disease), and low-grade intestinal T-cell lymphoma. While alterations in the gut metabolome have been extensively studied in humans and dogs with gastrointestinal disorders, little is known about the specific metabolic profile of cats with CE. As lipids take part in energy storage, inflammation, and cellular structure, investigating the lipid profile in cats with CE is crucial. This study aimed to measure fecal concentrations of various fatty acids, sterols, and bile acids. Fecal samples from 56 cats with CE and 77 healthy control cats were analyzed using gas chromatography-mass spectrometry, targeting 12 fatty acids, 10 sterols, and 5 unconjugated bile acids. Fecal concentrations of nine targeted fatty acids and animal-derived sterols were significantly increased in cats with CE. However, fecal concentrations of plant-derived sterols were significantly decreased in cats with CE. Additionally, an increased percentage of primary bile acids was observed in a subset of cats with CE. These findings suggest the presence of lipid maldigestion, malabsorption, and inflammation in the gastrointestinal tract of cats with CE. Understanding the lipid alterations in cats with CE can provide insights into the disease mechanisms and potential future therapeutic strategies.

ObjectivesPrevious studies have identified various bacterial taxa that are altered in cats with chronic enteropathies (CE) vs healthy cats. Therefore, the aim of this study was to develop a targeted quantitative molecular method to evaluate the fecal microbiota of cats.MethodsFecal samples from 80 client-owned healthy cats and 68 cats with CE were retrospectively evaluated. A panel of quantitative PCR (qPCR) assays was used to measure the fecal abundance of total bacteria and seven bacterial taxa: Bacteroides, Bifidobacterium, Clostridium hiranonis, Escherichia coli, Faecalibacterium, Streptococcus and Turicibacter. The nearest centroid classifier algorithm was used to calculate a dysbiosis index (DI) based on these qPCR abundances.ResultsThe abundances of total bacteria, Bacteroides, Bifidobacterium, C hiranonis, Faecalibacterium and Turicibacter were significantly decreased, while those of E coli and Streptococcus were significantly increased in cats with CE (P 0.Conclusions and relevanceA qPCR-based DI for assessing the fecal microbiota of cats was established. The results showed that a large proportion of cats with CE had an altered fecal microbiota as evidenced by an increased DI. Prospective studies are warranted to evaluate the utility of this assay for clinical assessment of feline CE.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Differentiation between IBD and SCL can be diagnostically challenging. We characterized the fecal metabolome of 14 healthy cats and 22 cats with naturally occurring CE (11 cats with IBD and 11 cats with SCL). Principal component analysis and heat map analysis showed distinct clustering between cats with CE and healthy controls. Random forest classification revealed good group prediction for healthy cats and cats with CE, with an overall out-of-bag error rate of 16.7%. Univariate analysis indicated that levels of 84 compounds in cats with CE differed from those in healthy cats. Polyunsaturated fatty acids held discriminatory power in differentiating IBD from SCL. Metabolomic profiles of cats with CE resembled those in people with CE with significant alterations of metabolites related to tryptophan, arachidonic acid, and glutathione pathways.

BackgroundIntegrating immunohistochemistry (IHC) and clonality testing with histopathology may improve the ability to differentiate inflammatory bowel disease (IBD) and alimentary small cell lymphoma (LSA) in cats.Hypothesis/objectivesTo evaluate the utility of histopathology, IHC, and clonality testing to differentiate between IBD and LSA and agreement of diagnostic results for endoscopic biopsy (EB) samples from the upper (USI) and lower small intestine (LSI).AnimalsFifty-seven cats with IBD or LSA.MethodsAll cases were categorized as definitive IBD (DefIBD), possible LSA (PossLSA), probable LSA (ProbLSA), or definitive LSA (DefLSA) based on histopathology alone. Results from IHC and clonality testing were integrated.ResultsBased on histopathology alone, 24/57 (42.1%), 15/57 (26.3%), and 18/57 (31.6%) cats were diagnosed with DefIBD, PossLSA or ProbLSA, and DefLSA, respectively. After integrating IHC and clonality testing, 11/24 cases (45.8%) and 15/15 cases (100%) previously categorized as DefIBD and PossLSA or ProbLSA, respectively, were reclassified as LSA. A final diagnosis of IBD and LSA was reported in 13/57 (22.8%) and 44/57 (77.2%) cats, respectively. Agreement between USI and LSI samples was moderate based on histopathology alone (κ = 0.66) and after integrating IHC and clonality testing (κ = 0.70). However, only 1/44 (2.3%) of the LSA cases was diagnosed based on LSI biopsy alone.Conclusions and clinical importanceIntegrating IHC and clonality testing increased the number of cases diagnosed with LSA, but the consequence for patient outcome is unclear. There was moderate agreement between USI and LSI samples. Samples from the LSI rarely changed the diagnosis.

BackgroundCurrent tests for diagnosis and differentiation of lymphoplasmacytic enteritis (LPE) and small cell lymphoma (SCL) in cats are expensive, invasive, and lack specificity. The identification of less invasive, more reliable biomarkers would facilitate diagnosis.ObjectivesTo characterize the mucosal proteome in endoscopically obtained, small intestinal tissue biopsy specimens. We hypothesized that differentially expressed proteins could be identified and serve as biomarker candidates for the differentiation of LPE and SCL in cats.AnimalsSix healthy control cats, 6 cats with LPE, and 8 cats with SCL.MethodsThe mucosal proteome was analyzed using 2-dimensional fluorescence difference gel electrophoresis (2D DIGE) and nanoflow liquid chromatography tandem mass spectrometry. For 5 proteins, results were verified by Western blot analysis.ResultsA total of 2349 spots were identified, of which 9 were differentially expressed with a ≥2-fold change between healthy cats and cats with LPE and SCL (.01 < P

BackgroundDifferentiation of lymphocytic-plasmacytic enteropathy (LPE) from small cell lymphoma (SCL) in cats can be challenging.Hypothesis/objectiveHistology-guided mass spectrometry (HGMS) is a suitable method for the differentiation of LPE from SCL in cats.AnimalsForty-one cats with LPE and 52 cats with SCL.MethodsThis is a retrospective clinicopathologic study. Duodenal tissue samples of 17 cats with LPE and 22 cats with SCL were subjected to HGMS, and the acquired data were used to develop a linear discriminate analysis (LDA) machine learning algorithm. The algorithm was subsequently validated using a separate set of 24 cats with LPE and 30 cats with SCL. Cases were classified as LPE or SCL based on a consensus by an expert panel consisting of 5-7 board-certified veterinary specialists. Histopathology, immunohistochemistry, and clonality testing were available for all cats. The panel consensus classification served as a reference for the calculation of test performance parameters.ResultsRelative sensitivity, specificity, and accuracy of HGMS were 86.7% (95% confidence interval [CI]: 74.5%-98.8%), 91.7% (95% CI: 80.6%-100%), and 88.9% (95% CI: 80.5%-97.3%), respectively. Comparatively, the clonality testing had a sensitivity, specificity, and accuracy of 85.7% (95% CI: 72.8%-98.7%), 33.3% (95% CI: 14.5%-52.2%), and 61.5% (95% CI: 48.3%-74.8%) relative to the panel decision.Conclusions and clinical importanceHistology-guided mass spectrometry was a reliable technique for the differentiation of LPE from SCL in duodenal formalin-fixed paraffin-embedded samples of cats and might have advantages over tests currently considered state of the art.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Both IBD and SCL in cats share features with chronic enteropathies such as IBD and monomorphic epitheliotropic intestinal T-cell lymphoma in humans. The aim of this study was to characterize the fecal microbiome of 38 healthy cats and 27 cats with CE (13 cats with IBD and 14 cats with SCL). Alpha diversity indices were significantly decreased in cats with CE (OTU p = 0.003, Shannon Index p = 0.008, Phylogenetic Diversity p = 0.019). ANOSIM showed a significant difference in bacterial communities, albeit with a small effect size (P = 0.023, R = 0.073). Univariate analysis and LEfSE showed a lower abundance of facultative anaerobic taxa of the phyla Firmicutes (families Ruminococcaceae and Turicibacteraceae), Actinobacteria (genus Bifidobacterium) and Bacteroidetes (i.a. Bacteroides plebeius) in cats with CE. The facultative anaerobic taxa Enterobacteriaceae and Streptococcaceae were increased in cats with CE. No significant difference between the microbiome of cats with IBD and those with SCL was found. Cats with CE showed patterns of dysbiosis similar to those in found people with IBD.

BackgroundHistopathology, immunohistochemistry, and molecular clonality testing are metrics frequently used to diagnose chronic enteropathy (CE) in cats. However, normal values for these metrics have been based mainly on samples from cats that were relatively young, specific pathogen-free, or both.ObjectivesTo describe results of histopathology, immunohistochemistry, and clonality testing of endoscopically-derived biopsy specimens of the upper small intestinal tract from a cohort of clinically healthy client-owned cats.AnimalsTwenty clinically healthy client-owned cats ≥3 years of age.MethodsTissue specimens were collected from the stomach and duodenum and evaluated single blinded by a board-certified pathologist. In addition, samples were evaluated by routine immunohistochemistry and clonality testing. Cats were followed after the procedure for signs of CE.ResultsIntegrated results from histopathology, immunohistochemistry, and clonality testing were interpreted as consistent with small cell lymphoma (SCL; n = 12), emerging SCL (n = 1), lymphocytic enteritis (n = 6), and pseudoclonality (n = 1). On follow-up, 3 cats eventually developed clinical signs of CE, of which 2 were euthanized 295 and 654 days post-endoscopy. The remaining 17 cats did not show clinical signs of CE after a median of 709 days (range, 219-869 days).Conclusions and clinical importanceIntestinal biopsy specimens from clinically healthy client-owned cats commonly had abnormal findings on histopathology, immunohistochemistry, clonality testing, or some combination of these without apparent clinical relevance. Current diagnostic metrics for diagnosing CE in cats may need modification to be applicable to the general population of cats.

Background: No prospective study has evaluated the efficacy of oral supplementation with cobalamin in hypocobalaminemic cats. Objectives: To investigate the efficacy of oral or SC supplementation with cyanocobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in hypocobalaminemic cats with chronic gastrointestinal disease (CGID) or exocrine pancreatic insufficiency (EPI). Animals: Forty‐eight client‐owned hypocobalaminemic (<290 ng/L) cats with normal or abnormally high serum MMA concentrations. Methods: This study was conducted based on the prospective randomized clinical trial method. Cats with CGID or EPI were randomly assigned to 2 groups that received either oral or SC supplementation with cobalamin (250 μg/cat) for 12 and 10 weeks, respectively, in addition to other medical and dietary interventions. Each cat was evaluated 3 times (baseline, 6‐week postsupplementation, and 1‐week postcompletion) by measuring serum cobalamin and MMA concentrations. Results: In cats with CGID or EPI, cobalamin concentrations were normalized in all cats that received either oral or SC supplementation (mean 100% [95% CI: 80.6%‐100%] in both groups in cats with CGID and 100% [67.6%‐100%] in both groups in cats with EPI). Among 37 cats with elevated MMA concentrations at baseline (21 cats with CGID and 16 cats with EPI), MMA concentrations were normalized in most cats with CGID (70% in oral and 82% in SC group) or EPI (88% in both groups). Conclusions and Clinical Importance: In hypocobalaminemic cats with CGID or EPI, in conjunction with other medical and dietary interventions, both oral and SC supplementation are effective at normalizing serum cobalamin and MMA concentrations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]