Unbiased serum metabolomic analysis in cats with naturally occurring chronic enteropathies before and after medical intervention
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ABSTRACT:
SUBMITTER: Questa M
PROVIDER: S-EPMC10960826 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC8080598 | biostudies-literature
Project description:IntroductionDegenerative joint disease (DJD) occurs very commonly in cats and can be associated with pain. Almost 70% of cats with DJD-associated pain suffer the co-morbidity of chronic kidney disease (CKD). There are currently very limited treatment or management options. A greater understanding of the systems biology of DJD, DJD-associated pain, and CKD may contribute to identifying disease specific biomarkers and relevant targets for the development of therapeutics for the control of these conditions in cats, and help inform human pain therapeutic development.MethodsUsing mass spectrometry-based proteomic profiling of the serum of 200 highly phenotyped cats with varying burdens of DJD, pain, and CKD, we identified significant individual proteins and pathways.ResultsFunctional pathway analysis, based on differentially abundant proteins across individual disease states (DJD, pain, CKD), identified pathways playing a role in DJD and DJD-associated pain including acute phase response signaling, LXR/RXR and FXR/RXR activation and the complement system. With the added co-morbidity of CKD, similar pathways were identified, with the addition of IL-12 signaling and production in macrophages.DiscussionWe identified differentially abundant proteins associated with DJD, pain and CKD and future work should evaluate these proteins as potential biomarkers of disease (individually or as clusters). Further, these data could be leveraged to identify novel therapeutic targets to address the gap in our ability to manage DJD, pain, and CKD in cats. Given that our work was in cats with naturally occurring DJD, these results may have translational applicability to human health.
| S-EPMC11832531 | biostudies-literature
Project description:BackgroundSoluble-type hemojuvelin in serum and urine has been shown to be a biomarker in humans for chronic kidney disease (CKD) and acute kidney injury (AKI). No similar research has been conducted on cats.ObjectiveUrine hemojuvelin (u-hemojuvelin) can be used as a clinical indicator for cats with various renal diseases.AnimalsEighteen healthy cats, 10 cats with AKI, 21 cats with acute-on-chronic kidney injury (ACKI), and 45 cats with CKD were enrolled.MethodsThe expression profile of u-hemojuvelin was assessed by Western blot analysis, whereas the u-hemojuvelin concentration was measured using an in-house sandwich ELISA. Each cat's u-hemojuvelin-to-creatinine ratio (UHCR) also was determined.ResultsSignificant differences were found in both u-hemojuvelin concentration and UHCR between the control cats and the other cats (AKI, CKD, ACKI). Both u-hemojuvelin and UHCR had high areas under the receiver operator curve (AUROC) for diagnoses of AKI (u-hemojuvelin, 0.885; UHCR, 0.982), CKD (hemojuvelin, 0.869; UHCR, 0.959), and ACKI (hemojuvelin, 0.910; UHCR, 1). Late stage (International Renal Interest Society, IRIS stages 3 and 4) CKD cats had significantly higher u-hemojuvelin concentration and UHCR than did early stage cats (IRIS stages 1 and 2). Both u-hemojuvelin and UHCR were significantly correlated with high blood urea nitrogen, plasma creatinine, and plasma phosphate concentrations and with low hematocrit (Hct), red blood cell (RBC) count, and plasma albumin concentration. The UHCR values were also significantly correlated with white blood cell count in blood.ConclusionBoth u-hemojuvelin and UHCR potentially can serve as diagnostic indicators for a range of renal diseases in cats.
| S-EPMC7255673 | biostudies-literature
Project description:ObjectivesThis study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design.MethodsTwenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%.ResultsPhase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed.ConclusionOutcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.
| S-EPMC5389833 | biostudies-literature
Project description:Background and aimsThe heart is a metabolic organ rich in mitochondria. The failing heart reprograms to utilize different energy substrates, which increase its oxygen consumption. These adaptive changes contribute to increased oxidative stress. Hypertrophic cardiomyopathy (HCM) is a common heart condition, affecting approximately 15% of the general cat population. Feline HCM shares phenotypical and genotypical similarities with human HCM, but the disease mechanisms for both species are incompletely understood. Our goal was to characterize global changes in metabolome between healthy control cats and cats with different stages of HCM.MethodsSerum samples from 83 cats, the majority (70/83) of which were domestic shorthair and included 23 healthy control cats, 31 and 12 preclinical cats with American College of Veterinary Internal Medicine (ACVIM) stages B1 and B2, respectively, and 17 cats with history of clinical heart failure or arterial thromboembolism (ACVIM stage C), were collected for untargeted metabolomic analysis. Multiple linear regression adjusted for age, sex and body weight was applied to compare between control and across HCM groups.ResultsOur study identified 1253 metabolites, of which 983 metabolites had known identities. Statistical analysis identified 167 metabolites that were significantly different among groups (adjusted P < 0.1). About half of the differentially identified metabolites were lipids, including glycerophospholipids, sphingolipids and cholesterol. Serum concentrations of free fatty acids, 3-hydroxy fatty acids and acylcarnitines were increased in HCM groups compared with control group. The levels of creatine phosphate and multiple Krebs cycle intermediates, including succinate, aconitate and α-ketoglutarate, also accumulated in the circulation of HCM cats. In addition, serum levels of nicotinamide and tryptophan, precursors for de novo NAD+ biosynthesis, were reduced in HCM groups versus control group. Glutathione metabolism was altered. Serum levels of cystine, the oxidized form of cysteine and cysteine-glutathione disulfide, were elevated in the HCM groups, indicative of heightened oxidative stress. Further, the level of ophthalmate, an endogenous glutathione analog and competitive inhibitor, was increased by more than twofold in HCM groups versus control group. Finally, several uremic toxins, including guanidino compounds and protein bound putrescine, accumulated in the circulation of HCM cats.ConclusionsOur study provided evidence of deranged energy metabolism, altered glutathione homeostasis and impaired renal uremic toxin excretion. Altered lipid metabolism suggested perturbed structure and function of cardiac sarcolemma membrane and lipid signalling.
| S-EPMC11911622 | biostudies-literature
Project description:Hypocobalaminemia is common in cats with chronic enteropathy (FCE). However, the disruptions in cobalamin metabolism are not fully understood and may vary across species. Cobalamin is distributed to target tissues via binding to transcobalamin (TC) in blood, which has not been evaluated in cats. Thus, an in-house sandwich-ELISA was established to evaluate serum total TC concentrations in cats with FCE. Surplus sera served to analytically validate the assay, and serum TC concentrations were compared among cats with FCE and other diseases (gastrointestinal neoplasia, cholangiohepatopathy, and other neoplastic or non-neoplastic conditions) and healthy controls. Observed-to-expected ratios for serial dilutions ranged from 72.4 to 145.6% and were 75.1-126.7% for spiking-and-recovery. Intra- and inter-assay variability was <17.7% and <17.2% and the preliminary reference interval for feline serum TC was <160-2795 aU/L (lower detection limit: 160 aU/L). Serum TC levels were significantly decreased (p = 0.0067) but not correlated with paired cobalamin concentrations in FCE. Hypertranscobalaminemia predominated with hypercobalaminemia, reaching the highest levels in advanced-stage chronic kidney disease (CKD) cases. TC variations in cobalamin deficiency states with FCE may be linked to inflammation or autoantibodies. This and possible links between serum TC variation in FCE, intracellular cobalamin availability, response to supplementation, and concurrent CKD require further exploration.
| S-EPMC11599117 | biostudies-literature
Project description:BackgroundThe gastrointestinal (GI) microbiota has a strong impact on the health of cats and these populations can be altered in GI disease. Little research has been done to associate improvement in diarrhea with changes in GI microbiota.ObjectiveTo evaluate GI microbiota changes associated with diet change and related improvement in diarrhea in cats with chronic naturally occurring diarrhea.AnimalsFifteen adult Domestic Shorthair cats with naturally occurring chronic diarrhea.MethodsControlled crossover dietary trial for management of diarrhea. Fecal microbiome was assessed using 454-pyrosequencing. Relationships among fecal score (FS), diet, and microbiome were explored using partial least square method, partial least square method - discriminant analysis, and orthogonal partial least square method with discriminant analysis (OPLS-DA).ResultsDominant bacterial phyla included the Firmicutes and Bacteroidetes, followed by Fusobacteria, Proteobacteria, Tenericutes, and Actinobacteria. Orthogonal partial least squares (OPLS-DA) clustering showed significant microbial differences within cats when fed Diet X versus Diet Y, and with Diet Y versus baseline. Significant correlations were found between the microbiome and FSs. Those bacteria with the strongest correlation with FS included Coriobacteriaceae Slackia spp., Campylobacter upsaliensis, Enterobacteriaceae Raoultella spp., Coriobacteriaceae Collinsella spp., and bacteria of unidentified genera within the families of Clostridiales Lachnospiracea and Aeromonadales Succinivibrionacease, suggesting that increased numbers of these organisms may be important to gut health.Conclusions and clinical importanceAlterations in intestinal microbiota were associated with improvement in diarrhea, but, from our data we cannot conclude if changes in the microbiome caused the improvement in diarrhea, or vice versa.
| S-EPMC4895530 | biostudies-literature
Project description:BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early prediction of renal damage and the progression of chronic kidney disease (CKD) in humans and dogs.HypothesisNeutrophil gelatinase-associated lipocalin also may play a role in the progression of CKD in cats.AnimalsEighty CKD and 18 control cats.MethodsCats were categorized into different stages according to the International Renal Interest Society (IRIS) staging system. Urine and plasma samples were collected and tested for NGAL concentrations using an in-house sandwich ELISA system and urinary NGAL (uNGAL)-to-creatinine ratio (UNCR) was determined. Cats in which serum creatinine concentration increased by >0.5 mg/dL from baseline within 30 days were defined as exhibiting progression.ResultsThe urinary NGAL and UNCR of CKD cats were significantly higher than those of healthy cats (P < .05) and were highly correlated with serum creatinine concentration. The area under the receiver operating characteristic curve (AUROC) for uNGAL, when predicting the progression of CKD, was 0.71 and the best cutoff value was 2.06 ng/mL with a sensitivity of 76.9% and a specificity of 75%. The AUROC for UNCR when predicting the progression of CKD was 0.79 and the best cutoff value was 4.08 × 10-6 with a sensitivity of 76.9% and specificity of 79.2%. Cats with UNCR values higher than their cutoffs experienced significantly faster deterioration with a median of 19 days.ConclusionsBoth urinary NGAL and UNCR are useful markers for the prediction of CKD progression in cats.
| S-EPMC5259624 | biostudies-literature
Project description:IgA is the most abundantly produced antibody and plays an important role in the mucosal immune system. Human IgA is represented by two isotypes, IgA1 and IgA2. The major structural difference between these two subclasses is the presence of nine potential sites of O-glycosylation in the hinge region between the first and second constant region domains of the heavy chain. Thr(225), Thr(228), Ser(230), Ser(232) and Thr(236) have been identified as the predominant sites of O-glycan attachment. The range and distribution of O-glycan chains at each site within the context of adjacent sites in this clustered region create a complex heterogeneity of surface epitopes that is incompletely defined. We previously described the analysis of IgA1 O-glycan heterogeneity by use of high resolution LC-MS and electron capture dissociation tandem MS to unambiguously localize all amino acid attachment sites in IgA1 (Ale) myeloma protein. Here, we report the identification and elucidation of IgA1 O-glycopeptide structural isomers that occur based on amino acid position of the attached glycans (positional isomers) and the structure of the O-glycan chains at individual sites (glycan isomers). These isomers are present in a model IgA1 (Mce1) myeloma protein and occur naturally in normal human serum IgA1. Variable O-glycan chains attached to Ser(230), Thr(233) or Thr(236) produce the predominant positional isomers, including O-glycans composed of a single GalNAc residue. These findings represent the first definitive identification of structural isomeric IgA1 O-glycoforms, define the single-site heterogeneity for all O-glycan sites in a single sample, and have implications for defining epitopes based on clustered O-glycan variability.
| S-EPMC3844682 | biostudies-literature
Project description:ObjectivesThe aim of the study was to determine the efficacy of the low struvite relative supersaturation diet in dissolution of feline struvite cystoliths.MethodsThis was a prospective, open-label, two-center study. Twelve client-owned cats were enrolled based on the radiographic appearance of their uroliths and urinalysis parameters. Cats were fed the test diet exclusively for up to 56 days. Cats were radiographed every other week until radiographic evidence of dissolution occurred or the end of the study period was reached. Cats with radiographically apparent uroliths at the end of the study period underwent cystotomy for stone retrieval and analysis.ResultsNine of the 12 cats completed the study. Eight experienced radiographic dissolution; seven of these had complete dissolution within the first month of treatment. One cat, whose owner declined cystotomy after partial dissolution at day 56, had complete radiographic resolution at 70 days of treatment. Two calcium oxalate urolith cores were removed from a cat that had partial radiographic dissolution.Conclusions and relevanceThe test diet was successful in dissolving suspected struvite cystoliths. As this diet is suitable for maintenance feeding of adult cats, it may be a suitable choice for long-term prevention of feline struvite urolithiasis.
| S-EPMC8008402 | biostudies-literature