Canine Chronic Enteropathies Research Articles

Evaluation of the relationship between plasma glucagon-like peptide-2 and gastrointestinal dysbiosis in canine chronic enteropathies.

Chronic enteropathies are a common cause of morbidity in dogs and are associated with disruption of the normal gastrointestinal mucosal barrier. The objective of this prospective study was to determine the association between measures of gastrointestinal dysbiosis and plasma concentrations of glucagon-like peptide-2, a hormone responsible for normal mucosal structure, in dogs with chronic enteropathies. Fecal 16S V4 rRNA gene sequencing and quantitative PCR via the dysbiosis index was performed on 16 healthy controls and 18 dogs with chronic enteropathy prior to and 1 month after initiation of individualized therapy. Fasting and post-prandial plasma GLP-2 concentrations were measured via ELISA in healthy dogs and chronic enteropathy dogs at both time points. Alpha and beta diversity indices, as well as bacterial population abundances were compared between groups and time-points. Principal component analysis combined with least squares regression was used to identify taxa contributing to glucagon-like peptide-2 variance among groups. While the dysbiosis index did not differ between healthy dogs and dogs with chronic enteropathy, 16S V4 genomic sequencing identified 47 operational taxonomic units that differed between the groups, all but 2 of which resolved following chronic enteropathy treatment. Principal component analysis identified 6 families and 19 genera that contributed to differences in glucagon-like peptide-2 concentrations between groups. Dysbiosis associated with chronic enteropathies in dogs may contribute to the observed lower plasma glucagon-like peptide-2 concentrations. Further research into mechanisms of microbiota impact on the enteroendocrine system is needed. Association between glucagon-like peptide-2 secretion and microbiome indices may help to guide research into future treatment strategies for dogs with chronic enteropathy.

Clinical applications of current biomarkers in canine chronic enteropathies

Chronic enteropathies (CEs) are a group of multifactorial gastrointestinal diseases in dogs, which are defined by chronic persistent or recurrent gastrointestinal symptoms, along with histopathological indications of mucosal inflammation. These disorders have gained significant interest in recent years due to their unclear etiopathogenesis, the severity of symptoms and lack of response to conventional treatments. The diagnosis of canine CEs is challenging because of their non-specific clinical symptoms, which require an extensive diagnostic investigations to exclude alternative causes of chronic gastrointestinal signs. Currently, the gold standard for diagnosing CEs relies on histopathologic evaluation and assessing responses to therapeutic trials. However, these methods have limitations in terms of invasiveness, cost and time consumption. Therefore, biological markers that objectively reflect the severity of gastrointestinal disease, assist in diagnosing clinical practice, predicting treatment response, determining prognosis and monitoring disease progression may offer valuable clinical benefits for dogs with CEs. This article provides an overview of the current biomarkers for canine CEs and discusses their potential clinical applications, as well as their advantages and limitations. Furthermore, this review expects to contribute to the identification of future directions for advancing biomarkers in canine CEs research.

Changes of Enterocyte Morphology and Enterocyte: Goblet Cell Ratios in Dogs with Protein-Losing and Non-Protein-Losing Chronic Enteropathies.

This study aimed to assess the morphometry of enterocytes as well as the goblet cell-to-enterocyte ratio in different intestinal segments of dogs with chronic enteropathies (CE). Histopathological intestinal samples from 97 dogs were included in the study (19 healthy juveniles, 21 healthy adults, 24 dogs with protein-losing enteropathy (PLE), and 33 CE dogs without PLE). Healthy adult small intestinal enterocytes showed progressively reduced epithelial cell height in the aboral direction, while juvenile dogs showed progressively increased epithelial cell height in the aboral direction. CE dogs had increased epithelial cell height in the duodenum, while PLE dogs had decreased epithelial cell heights compared to healthy adult dogs. Both the CE and PLE dogs showed decreased enterocyte width in the duodenal segment, and the ileal and colonic enterocytes of CE dogs were narrower than those of healthy adult dogs. CE dogs had a lower goblet cell-to-enterocyte ratio in the colon segment compared to healthy dogs. This study provides valuable morphometric information on enterocytes during canine chronic enteropathies, highlighting significant morphological enterocyte alterations, particularly in the small intestine, as well as a reduced goblet cell-to-enterocyte ratio in the colon of CE cases compared to healthy adult dogs.

Home-cooked diets cost more than commercially prepared dry kibble diets for dogs with chronic enteropathies

Nutrition plays a fundamental role in the management of canine chronic enteropathies (CCEs). Dog owners may elect to feed home-cooked diets (HCDs) rather than veterinary commercially prepared diets (CPDs) because of perceived lower costs. There is a paucity of data comparing costs of these options. We hypothesize there will be differences in costs between complete and balanced HCDs and nutritionally comparable CPDs. 6 Home-cooked diets. Six HCD recipes (2 highly digestible, 2 limited antigen, 2 low-fat) were formulated by 2 board-certified veterinary nutritionists to mimic the nutritional and ingredient profiles of veterinary CPDs for management of CCEs. The cost (in US$ on a per 100 kilocalorie [kcal] basis) of each recipe was determined via collection of ingredient prices from 3 grocery stores combined with supplement prices from online retailers. Prices of CPDs were obtained from a national online retailer. Maintenance energy requirements of 1.6 X (70 X BWkg0.75), where BWkg represents body weight in kilograms, were calculated for 3 dog sizes (5, 20, and 40 kg), and costs of feeding maintenance energy requirements with HCDs versus dry and canned CPDs were compared with a Kruskal-Wallis test and post hoc testing. The median costs of all dry and canned CPDs and HCDs were $0.29 (range, $0.18 to $0.46), $1.01 (range, $0.77 to $1.20), and $0.55 (range, $0.35 to $1.14), respectively. Feeding complete and balanced HCDs cost more than feeding dry CPDs (P < .001), but not canned CPDs (P > .99). Dry CPDs cost the least for nutritional management of CCEs. There is a wide range of costs for both CPDs and HCDs.

Machine Learning and Canine Chronic Enteropathies: A New Approach to Investigate FMT Effects.

Simple SummaryFecal microbiota transplantation (FMT) represents a very promising approach to decrease disease activity in chronic enteropathies (CE). Although CE and dysbiosis are undoubtedly connected, the relationship between remission mechanisms and microbiome changes has not been elucidated yet. Indeed, CE is a heterogeneous disease consisting of many different subtypes, and the dynamic of the microbial community is very complex. The aim of this study was to report the clinical effects of oral freeze-dried FMT in dogs affected by CE, analyzing the fecal microbiome before and after FMT, and comparing the microbial composition with a healthy population. Artificial intelligence algorithms were applied to address the high complexity of microbiomes. Clinical signs of improvement were observed in three-quarters of receivers, proving the effectiveness of the treatment in the freeze-dried form. Machine learning algorithms successfully predicted healthy and diseased animal categories, using microbial compositions. Every receiver showed microbiome variation after the transplant, but there was high heterogeneity in the response. These findings are the first step for further research on a larger dataset that could identify different healing patterns of microbiome changes.Fecal microbiota transplantation (FMT) represents a very promising approach to decreasing disease activity in canine chronic enteropathies (CE). However, the relationship between remission mechanisms and microbiome changes has not been elucidated yet. The main objective of this study was to report the clinical effects of oral freeze-dried FMT in CE dogs, comparing the fecal microbiomes of three groups: pre-FMT CE-affected dogs, post-FMT dogs, and healthy dogs. Diversity analysis, differential abundance analysis, and machine learning algorithms were applied to investigate the differences in microbiome composition between healthy and pre-FMT samples, while Canine Chronic Enteropathy Clinical Activity Index (CCECAI) changes and microbial diversity metrics were used to evaluate FMT effects. In the healthy/pre-FMT comparison, significant differences were noted in alpha and beta diversity and a list of differentially abundant taxa was identified, while machine learning algorithms predicted sample categories with 0.97 (random forest) and 0.87 (sPLS-DA) accuracy. Clinical signs of improvement were observed in 74% (20/27) of CE-affected dogs, together with a statistically significant decrease in CCECAI (median value from 5 to 2 median). Alpha and beta diversity variations between pre- and post-FMT were observed for each receiver, with a high heterogeneity in the response. This highlighted the necessity for further research on a larger dataset that could identify different healing patterns of microbiome changes.

Preliminary evaluation of serum zonulin in canine chronic enteropathies.

In humans, serum zonulin, a biomarker of intestinal permeability, correlates with underlying enteropathies and has potential application as a therapeutic target. The aim of this study was to evaluate serum zonulin as a biomarker for canine chronic enteropathy. Prospective enrolment of twenty-one client-owned dogs with at least 1 of the following gastrointestinal (GI) signs for at least 3 weeks duration: anorexia, hyporexia, dysrexia, vomiting, weight loss or diarrhea. 21 control dogs, age and breed matched, were also enrolled. Dogs with gastrointestinal signs were diagnosed with chronic enteropathy based on a complete blood count, serum chemistry, specific canine pancreatic lipase, cobalamin, resting cortisol, abdominal ultrasound and gastrointestinal endoscopy with histopathology. Enrolled control dogs had an unremarkable physical examination, complete blood count, serum chemistry and no clinical signs of gastrointestinal disease. Dogs were ineligible if antibiotics or immunosuppressive medications were administered within 1 month of enrolment. Blood samples were analysed using a commercial canine serum zonulin quantitative ELISA. Dogs with chronic enteropathies had median serum zonulin values of 0.28 ng/mL (interquartile range: 0.04-2.59), while control dogs of 0.27 ng/mL (0.05-3.67). There was no significant difference in canine serum zonulin levels between these populations. The estimated difference in the median concentrations was -0.01 ng/mL (95% CI: -0.23 to 0.89). In this study, using a commercial canine zonulin ELISA, serum zonulin levels did not differentiate between dogs with chronic enteropathies and control dogs.

Faecal proteomics in the identification of biomarkers to differentiate canine chronic enteropathies

Canine chronic enteropathy (CCE) is a collective term used to describe a group of idiopathic enteropathies of dogs that result in a variety of clinical manifestations of intestinal dysfunction. Clinical stratification into food-responsive enteropathy (FRE) or non-food responsive chronic inflammatory enteropathy (CIE), is made retrospectively based on response to treatments. Faecal extracts from those with a FRE (n = 5) and those with non-food responsive chronic inflammatory enteropathies (CIE) (n = 6) were compared to a healthy control group (n = 14) by applying TMT-based quantitative proteomic approach. Many of the proteins with significant differential abundance between groups were pancreatic or intestinal enzymes with pancreatitis-associated protein (identified as REG3α) and pancreatic M14 metallocarboxypeptidase proteins carboxypeptidase A1 and B identified as being of significantly increased abundance in the CCE group. The reactome analysis revealed the recycling of bile acids and salts and their metabolism to be present in the FRE group, suggesting a possible dysbiotic aetiology. Several acute phase proteins were significantly more abundant in the CCE group with the significant increase in haptoglobin in the CIE group especially notable. Further research of these proteins is needed to fully assess their clinical utility as faecal biomarkers for differentiating CCE cases. SignificanceThe identification and characterisation of biomarkers that differentiate FRE from other forms of CIE would prove invaluable in streamlining clinical decision-making and would avoid costly and invasive investigations and delays in implementing effective treatment. Many of the proteins described here, as canine faecal proteins for the first time, have been highlighted in previous human and murine inflammatory bowl disease (IBD) studies initiating a new chapter in canine faecal biomarker research, where early and non-invasive biomarkers for early clinical stratification of CCE cases are needed. Pancreatitis-associated protein, pancreatic M14 metallocarboxypeptidase along with carboxypeptidase A1 and B are identified as being of significantly increased abundance in the CCE groups. Several acute phase proteins, were significantly more abundant in the CCE group notably haptoglobin in dogs with inflammatory enteropathy. The recognition of altered bile acid metabolism in the reactome analysis in the FRE group is significant in CCE which is a complex condition incorporating of immunological, dysbiotic and faecal bile acid dysmetabolism. Both proteomics and immunoassays will enable the characterisation of faecal APPs as well as other inflammatory and immune mediators, and the utilisation of assays, validated for use in analysis of faeces of veterinary species will enable clinical utilisation of faecal matrix to be fully realised.

Current diagnostics for chronic enteropathies in dogs.

Chronic enteropathies (CEs) in dogs describe a group of idiopathic disorders characterized by chronic persistent or recurrent gastrointestinal (GI) signs. Three major subgroups of CE can be identified by their response to treatment: Food-responsive disease (FRD), antibiotic-responsive disease (ARD), and steroid-responsive disease (SRD). The clinical diagnosis of CE is made by exclusion of all other possible causes of chronic diarrhea and includes histologic assessment of intestinal biopsies. The process of diagnosing canine CE can therefore be very time-consuming and expensive, and in most cases, does not help to identify dogs that will respond to a specific treatment. The development of novel diagnostic tests for canine CE has therefore focused on the accuracy of such tests to predict treatment responses. In this article, several novel assays that have the potential to become commercially available will be discussed, such as genetic tests, perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), antibodies against transglutaminase/gliadin, antibodies against E coli OmpC/flagellin, and micro RNAs.

The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy.

Simple SummaryMolecular-based approaches are rapidly developing in medicine for the evaluation of physiological and pathological conditions and for the discovery of new biomarkers in prevention and therapy. Membrane fatty acid-based lipidomic analysis in healthy animals provides a benchmark to study disease conditions and was useful to evidence significant differences in dogs affected by chronic enteropathy. Such molecular information might have the potential to become a useful tool in the assessment of canine chronic enteropathy, being connected with nutritional and metabolic status of the subjects, as well as it may reflect “gut health” and suggest appropriate intervention by “lipid therapy”.Canine chronic enteropathies (CEs) are inflammatory processes resulting from complex interplay between the mucosal immune system, intestinal microbiome, and dietary components in susceptible dogs. Fatty acids (FAs) play important roles in the regulation of physiologic and metabolic pathways and their role in inflammation seems to be dual, as they exhibit pro–inflammatory and anti–inflammatory functions. Analysis of red blood cell (RBC) membrane fatty acid profile represents a tool for assessing the quantity and quality of structural and functional molecular components. This study was aimed at comparing the FA membrane profile, determined by Gas Chromatography and relevant lipid parameter of 48 CE dogs compared with 68 healthy dogs. In CE patients, the levels of stearic (p < 0.0001), dihomo–gamma–linolenic, eicosapentaenoic (p = 0.02), and docosahexaenoic (p = 0.02) acids were significantly higher, and those of palmitic (p < 0.0001) and linoleic (p = 0.0006) acids were significantly lower. Non-responder dogs presented higher percentages of vaccenic acid (p = 0.007), compared to those of dogs that responded to diagnostic trials. These results suggest that lipidomic status may reflect the “gut health”, and the non–invasive analysis of RBC membrane might have the potential to become a candidate biomarker in the evaluation of dogs affected by CE.

The Impact of Chronic Inflammatory Enteropathy on Dogs' Quality of Life and Dog-Owner Relationship.

This research was aimed at evaluating the impact of canine chronic enteropathies on dogs’ quality of life (QoL), their behavior, and owner–dog relationship. Forty-four dogs suffering from primary chronic enteropathies were assessed on the first visit with a veterinary gastroenterologist and on the first follow-up visit using a 1–10 visual scale to evaluate five features of QoL, the Canine Chronic Enteropathy Clinical Activity Index, the Lexington Attachment to Pet Scale, and the Canine Behavioral Assessment and Research Questionnaire. They were compared to a control group of 49 healthy dogs and to a group of 50 dogs suffering from cancer. QoL and severity of enteropathy were negatively associated; enteropathic dogs on the first visit had a lower QoL than healthy dogs for all features and a lower general QoL than cancer patients; enteropathic dogs on the follow-up visit improved significantly for general QoL, health QoL, and interaction QoL. Higher levels of attachment between the owner and the dog were obtained for dogs affected by chronic enteropathies. Finally, dogs showed higher scores for separation-related behaviors and contact/attention behaviors on the first visit than on the subsequent follow-up. As in human medicine, chronic enteropathies have a strong negative impact on dogs.

Circulating Endocannabinoids as Diagnostic Markers of Canine Chronic Enteropathies: A Pilot Study.

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 N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamine (PEA), and N-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 (p = 0.001) and PEA (p = 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 (p = 0.04), while 2-AG was higher in IRE than in healthy dogs (p = 0.0001). Dogs affected by FRE also showed decreased 2-AG (p = 0.0001) and increased OEA levels (p = 0.0018) compared to IRE dogs. Moreover, dogs with PLE showed increased 2-AG (p = 0.033) and decreased AEA (p = 0.035), OEA (p = 0.016) and PEA (p = 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.

Circulating Endocannabinoids as Diagnostic Markers of Canine Chronic Enteropathies: A Pilot Study

Circulating Endocannabinoids as Diagnostic Markers of Canine Chronic Enteropathies: A Pilot Study

What are the potential biomarkers that should be considered in diagnosing and managing canine chronic inflammatory enteropathies?

Chronic inflammatory enteropathies in dogs are characterized by persistent or recurrent gastrointestinal signs that last for more than 3 weeks. Despite unclear etiopathogenesis, it is considered that a genetic predisposition associated with environmental factors, such as dietary antigens and intestinal microbiota, might induce an abnormal immune response in the host. The diagnosis of this condition requires full investigation in order to exclude all other possible causes. Currently, the observation of clinical signs associated with histopathologic evaluation and systematic therapeutic trials is the gold standard for the diagnosis of chronic enteropathies. Furthermore, diagnosis, monitoring the disease progression, and treatment response evaluation can be exhausting, since this whole process is time-consuming, costly, and partially invasive. Therefore, biomarkers appear as non-invasive tools, which can be useful in evaluating gastrointestinal function, identifying the presence of the disease and assessing its natural progression, monitoring gastrointestinal inflammation, predicting response to treatment, and clinical outcomes. Over the past decade, several studies were conducted in order to explore the clinical utility of biomarkers. Thus, the aim of this dissertation is to provide an overview of the biomarkers considered relevant in the diagnosis and management of dogs with chronic inflammatory enteropathies. The biomarkers addressed in this study may be serological, present in urine and feces, or even tissue-derived. This study argues that biomarkers, in particular calprotectin and calgranulin C, have great potential to be used in clinical practice in the diagnosis and management of affected dogs. However, a single biomarker cannot assuredly predict disease severity, progression, response to treatment, and clinical outcomes. Therefore, in order to achieve greater accuracy, it would be beneficial if these tools are used in conjunction with contemporary ones. Future research is needed with the aim to better determine the usefulness of these tools in chronic inflammatory enteropathies in dogs.

Administration of a Synbiotic Containing Enterococcus faecium Does Not Significantly Alter Fecal Microbiota Richness or Diversity in Dogs With and Without Food-Responsive Chronic Enteropathy

Background: Canine chronic enteropathies (CE) are a group of intestinal diseases that can be categorized based on treatment response into diet- or food- responsive enteropathy (FRD), antibiotic-responsive enteropathy, steroid-responsive enteropathy, and non-responsive enteropathy. CE can often be associated with intestinal dysbiosis and thus administration of probiotic or synbiotic products may provide a useful tool for the management of some of these patients. Enterococcus faecium (EF) is a probiotic strain included in a commercially available synbiotic for small animals, however its impact on the microbial communities in dogs with FRD has not yet been evaluated.Hypothesis/Objectives: The administration of a synbiotic will lead to a significant difference of the fecal microbial composition and/or diversity in dogs with FRD, and these changes are not attributable to diet change alone.Animals/Samples: Twelve dogs with FRD fed a hydrolyzed protein diet received either a synbiotic (EF, fructooligosaccharides, gum Arabic) or placebo. Fecal samples were taken before and 6 weeks into treatment. Fecal samples were also acquired from 8 healthy dogs before and 6 weeks after being switched to the same hydrolyzed protein diet as their sole food.Methods: Bacterial DNA was extracted from fecal samples and next generation sequencing based on the 16S rRNA genes was performed. Microbial composition and diversity between groups were compared using QIIME.Results: There was a small increase in species diversity in the feces of dogs with FRD treated with synbiotics. However, there were no significant differences in microbial community composition before and after 6 weeks in either the synbiotic or placebo treated dogs with FRD or the healthy dogs. In all groups, large individual variations were observed.Conclusions: No changes in microbial composition were observed in diseased or healthy dogs with diet change alone. However, administration of a synbiotic increased bacterial richness in both groups.

Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract.

The endocannabinoid system (ECS) is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in endocannabinoid turnover. Modulating the activity of the ECS may influence a variety of physiological and pathophysiological processes. A growing body of evidence indicates that activation of cannabinoid receptors by endogenous, plant-derived, or synthetic cannabinoids may exert beneficial effects on gastrointestinal inflammation and visceral pain. The present ex vivo study aimed to investigate immunohistochemically the distribution of cannabinoid receptors CB1, CB2, G protein-coupled receptor 55 (GPR55), and peroxisome proliferation activation receptor alpha (PPARα) in the canine gastrointestinal tract. CB1 receptor immunoreactivity was observed in the lamina propria and epithelial cells. CB2 receptor immunoreactivity was expressed by lamina propria mast cells and immunocytes, blood vessels, and smooth muscle cells. Faint CB2 receptor immunoreactivity was also observed in neurons and glial cells of the submucosal plexus. GPR55 receptor immunoreactivity was expressed by lamina propria macrophages and smooth muscle cells. PPARα receptor immunoreactivity was expressed by blood vessels, smooth muscle cells, and glial cells of the myenteric plexus. Cannabinoid receptors showed a wide distribution in the gastrointestinal tract of the dog. Since cannabinoid receptors have a protective role in inflammatory bowel disease, the present research provides an anatomical basis supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders and visceral hypersensitivity in canine acute or chronic enteropathies.

Identification of matrix metalloproteinase-2 and -9 activities within the intestinal mucosa of dogs with chronic enteropathies

BackgroundMatrix metalloproteinases (MMPs) 2 and 9 are zinc- and calcium-dependent endopeptidases involved in the breakdown and reconstitution of extracellular matrix under both physiological and pathological conditions. Mucosal MMP-2 and -9 activities have been reported to be upregulated in the intestine of humans with inflammatory bowel disease (IBD), and in animal models of IBD. However, their involvement in the pathogenesis of canine chronic enteropathies (CE) is unknown. This study investigated mucosal pro- and active MMP-2 and -9 activities in dogs with CE and healthy dogs using gelatin zymography, and also to determine the association of their activities in dogs with CE with the canine IBD activity index (CIBDAI), histopathologic findings, the clinical outcome, and hypoalbuminemia. Intestinal mucosal samples from duodenum, ileum, colon, and cecum were collected from 40 dogs with CE and 18 healthy Beagle dogs.ResultsIn dogs with CE, the number of samples positive for mucosal pro- and active MMP-2 was significantly higher in the duodenum (P < 0.0001 and P = 0.011, respectively), ileum (P = 0.002 and P = 0.018, respectively), and colon (P < 0.0001 and P = 0.002, respectively), compared with healthy controls. Mucosal pro-MMP-9-positive samples in the duodenum and colon were significantly more frequent in dogs with CE than in healthy dogs (P = 0.0004 and P = 0.001, respectively). Despite the presence of mucosal samples positive for active MMP-9 in the intestinal segments of dogs with CE, the difference compared to healthy controls did not reach statistical significance. None of the intestinal mucosal samples in healthy dogs showed gelatinolytic activity corresponding to the control bands of active MMP-2 and -9. Mucosal active MMP-9 activities displayed a significant positive association with the severity of neutrophil infiltration in the duodenum (P = 00.040), eosinophils in the cecum (P = 00.037), and the CIBDAI score for ileum samples (P = 0.023). There was no significant association of pro- and active MMP-2 and -9 levels with the clinical outcome or hypoalbuminemia.ConclusionsThis study is the first to demonstrate upregulation of mucosal pro- and active MMP-2 and pro-MMP-9 in the intestine of dogs with CE compared to healthy dogs. The results provide supporting evidence for the possible involvement of MMP-2 and -9 in the pathogenesis of canine CE.

Pattern-recognition receptors: signaling pathways and dysregulation in canine chronic enteropathies-brief review.

Pattern-recognition receptors (PRRs) are expressed by innate immune cells and recognize pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular pattern (DAMP) molecules. With a large potential for synergism or convergence between their signaling pathways, PRRs orchestrate a complex interplay of cellular mediators and transcription factors, and thus play a central role in homeostasis and host defense. Aberrant activation of PRR signaling, mutations of the receptors and/or their downstream signaling molecules, and/or DAMP/PAMP complex-mediated receptor signaling can potentially lead to chronic auto-inflammatory diseases or development of cancer. PRR signaling pathways appear to also present an interesting new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets. Evidence for a dysregulation of the PRR toll-like receptor (TLR)2, TLR4, TLR5, and TLR9, nucleotide-binding oligomerization domain-containing protein (NOD)2, and the receptor of advanced glycation end products (RAGE) exists in dogs with chronic enteropathies. We describe the TLR, NOD2, and RAGE signaling pathways and evaluate the current veterinary literature-in comparison to human medicine-to determine the role of TLRs, NOD2, and RAGE in canine chronic enteropathies.

Improving IBD in dogs through exercise

CONFIRMING inflammatory bowel disease (IBD) in dogs, which is often idiopathic, can be difficult and continues to confound in achieving a definitive diagnosis in dogs presenting with chronic enteropathies. It...

Alterations of the Ileal and Colonic Mucosal Microbiota in Canine Chronic Enteropathies.

BackgroundThe intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE) in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon.AimTo investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls.MethodsTissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD), 6 dogs with granulomatous colitis (GC), 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH) on a quantifiable basis.ResultsThe ileal and colonic mucosa of healthy dogs and dogs with CE is predominantly colonized by bacteria localized to free and adherent mucus compartments. CE dogs harbored more (P < 0.05) mucosal bacteria belonging to the Clostridium-coccoides/Eubacterium rectale group, Bacteroides, Enterobacteriaceae, and Escherichia coli versus controls. Within the CE group, IBD dogs had increased (P < 0.05) Enterobacteriaceae and E. coli bacteria attached onto surface epithelia or invading within the intestinal mucosa. Bacterial invasion with E. coli was observed in the ileal and colonic mucosa of dogs with GC (P < 0.05). Dogs with intestinal neoplasia had increased (P < 0.05) adherent (total bacteria, Enterobacteriaceae, E. coli) and invasive (Enterobacteriaceae, E. coli, and Bacteroides) bacteria in biopsy specimens. Increased numbers of total bacteria adherent to the colonic mucosa were associated with clinical disease severity in IBD dogs (P < 0.05).ConclusionPathogenic events in canine CE are associated with different populations of the ileal and colonic mucosal microbiota.

S100A12 concentrations and myeloperoxidase activity in the intestinal mucosa of healthy dogs.

BackgroundRelatively few laboratory markers have been evaluated for the detection or monitoring of intestinal inflammation in canine chronic enteropathies, including inflammatory bowel disease (IBD). Previous research found that the intestinal mucosal levels of S100A12 and myeloperoxidase (MPO), as biomarkers of gut inflammation, were elevated in human patients with IBD. To date, the S100A12 and MPO levels in intestinal mucosal samples from either healthy dogs or from dogs suffering from IBD remain unreported. Therefore, this study aimed to evaluate the mucosal S100A12 and MPO levels in four different parts of the intestine (duodenum, jejunum, ileum and colon) in 12 healthy laboratory Beagle dogs using the ELISA and spectrophotometric methods, respectively.ResultsBased on histological examinations, the recorded findings for all the samples were considered normal. The mucosal concentration of S100A12 in the ileum was significantly higher than in all other segments of the intestine (p < 0.05). MPO activity was significantly higher in the ileal, jejunal and duodenal than in colonic mucosal samples (p < 0.05). Moreover, its concentration was higher in the jejunum than in the duodenum.ConclusionsThis study showed that S100A12 and MPO are reliably detectable in canine intestinal mucosa. The assays used appeared to be sufficient to further evaluate the role of S100A12 and MPO in the pathogenesis of canine chronic enteropathies, including IBD. These biomarkers may play a role in the initial detection of gut inflammation suggesting the need for further investigations to confirm IBD or to differentiate between IBD subtypes. Understanding the role of S100A12 and MPO in the pathogenesis of chronic intestinal inflammation in future may result in an improved understanding of canine chronic intestinal inflammation.