Canine Inflammatory Bowel Disease Activity Research Articles

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

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. 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. 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. 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.

In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs?

PICO Question In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs or improving the canine inflammatory bowel disease (IBD) activity index (CIBDAI) or the canine chronic enteropathy clinical activity index (CCECAI)? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed One double-blinded randomised control trial. Strength of evidence Moderate. Outcomes reported The outcome of this study identified that no significant differences in remission rates (> 75% decrease in CIBDAI scores) were observed between the prednisone and budesonide groups. Frequency of adverse effects were also similar between the two groups. Conclusion A single study with moderate power of evidence alongside some significant limitations, particularly population size, cannot be used as the sole provider of an answer to the PICO question. As such, further studies with greater power would be required before a definitive assessment of comparative treatment efficacy can be made. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Oxidative stress in dogs with chronic inflammatory enteropathy treated with allogeneic mesenchymal stem cells

The search for new biomarkers in patients with chronic inflammatory enteropathy (CIE) is ongoing in the human and veterinary medicine fields. Oxidative stress biomarkers (malondialdehyde [MDA], reduced glutathione [GSH], and albumin) have been studied in humans with chronic enteropathies, but among them, only albumin has been studied in dogs with CIE. Moreover, the effect of mesenchymal stem cell (MSCs) treatment with or without prednisone on these parameters has never been studied in dogs with CIE. These parameters were compared between healthy dogs (n = 12) and dogs with CIE, and before and 1, 3, 6, and 12 months after the treatment with MSCs alone (n = 9) or together with prednisone (n = 11). The relationship between the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) and oxidative stress was evaluated. Albumin was the only parameter that significantly differed between dogs with CIE and healthy dogs (p = 0,037). Differences were observed only in albumin values after combined treatment with MSCs and prednisone. No differences were observed in MDA and GSH after treatment with MSCs with or without prednisone. Albumin could help stage canine CIE, as well as its prognosis, as has already been demonstrated, although it is essential to evaluate this parameter for its antioxidant capacity, and therefore it could be a good biomarker of oxidative stress in this pathology. However, the treatment with MSCs seems unable to modify any of the analyzed oxidative stress parameters.

Gut Bacterial Community Determines the Therapeutic Effect of Ginsenoside on Canine Inflammatory Bowel Disease by Modulating the Colonic Mucosal Barrier.

Inflammatory bowel disease (IBD) comprises systemic inflammatory conditions primarily affecting the gastrointestinal tract, including Crohn's disease and ulcerative colitis. This research aims to analyze the clinical symptoms and pathogenesis of a Dextran sodium sulfate (DSS)-induced canine IBD model and evaluate the restorative effect of ginsenoside from a pathogenesis perspective. We established the DSS-induced canine IBD model and studied the pathological mechanisms. Additionally, we examined the therapeutic effect of ginsenosides by assessing the Canine Inflammatory Bowel Disease Activity Index (CIBDAI), C-reactive protein (CRP) levels, colonic tissue morphology, protein expression, and mucosal bacterial community analysis. Our findings revealed a total ginsenoside content of 22.7% in the ginsenoside extract. Animal experiments demonstrated that dogs with IBD exhibited decreased mental state, significantly increased CIBDAI and CRP levels, disrupted colonic epithelial tissue structure, decreased expression of mucin, tight junctions, and adherens junctions, as well as reduced diversity of the colonic mucosal bacterial community. Furthermore, correlation analysis highlighted a total of 38 bacterial strains correlated with physiological indices. Significantly, ginsenoside treatment could improve these symptoms and reverse the relative abundance of some bacterial communities. In conclusion, alterations in the properties of the colonic mucus layer or the reduction in MUC2, its core component, in dogs with IBD can lead to bacterial penetration of the mucus layer and subsequent contact with intestinal epithelial cells, resulting in inflammation. Remarkably, ginsenoside intervention showcased the capacity to positively influence the relative abundance of bacteria and impact the colonic mucus layer properties, thereby offering promising prospects for IBD management and recovery.

Clinical Effects of Faecal Microbiota Transplantation as Adjunctive Therapy in Dogs with Chronic Enteropathies—A Retrospective Case Series of 41 Dogs

Chronic enteropathies (CE) are common in dogs, but not all affected dogs respond to standard therapy. Successful responses to faecal microbial transplantation (FMT) in dogs with non-responsive CE have been reported in two case series. The objective of this retrospective study was to describe the clinical effects of FMT as an adjunctive therapy in a larger population of dogs with CE. Forty-one dogs aged 0.6-13.0 years (median 5.8) under treatment for CE at one referral animal hospital were included. Dogs were treated with 1-5 (median 3) FMTs as a rectal enema at a dose of 5-7 g/kg body weight. The canine inflammatory bowel disease activity index (CIBDAI) was compared at baseline versus after the last FMT. Stored faecal samples (n = 16) were analysed with the dysbiosis index. CIBDAI at baseline was 2-17 (median 6), which decreased to 1-9 (median 2; p < 0.0001) after FMT. Subsequently, 31/41 dogs responded to treatment, resulting in improved faecal quality and/or activity level in 24/41 and 24/41 dogs, respectively. The dysbiosis index at baseline was significantly lower for good responders versus poor responders (p = 0.043). Results suggest that FMT can be useful as an adjunctive therapy in dogs with poorly responsive CE.

Changes in Faecal and Plasma Amino Acid Profile in Dogs with Food-Responsive Enteropathy as Indicators of Gut Homeostasis Disruption: A Pilot Study

Dogs suffering from food-responsive enteropathy (FRE) respond to an elimination diet based on hydrolysed protein or novel protein; however, studies regarding the amino acid profile in FRE dogs are lacking. The aim of this pilot study was to evaluate whether the plasma and faecal amino acid profiles differed between control and FRE dogs and whether these could serve as indicators of severity of illness. Blood, faecal samples, body condition score, and severity of clinical signs based on the canine inflammatory bowel disease activity index were collected before starting the elimination diet. FRE dogs had lower proportions of plasma Asparagine, Histidine, Glycine, Cystine, Leucine, and branched-chain/aromatic amino acids; however, Phenylalanine increased. In faecal samples, Cystine was greater whereas Phenylalanine was lesser in sick dogs compared to control. Leucine correlated negatively with faecal humidity (r = -0.66), and Leucine and Phenylalanine with faecal fat (r = -0.57 and r = -0.62, respectively). Faecal Phenylalanine (r = 0.80), Isoleucine (r = 0.75), and Leucine (r = 0.92) also correlated positively with total short-chain fatty acids, whereas a negative correlation was found with Glycine (r = -0.85) and Cystine (r = -0.61). This study demonstrates the importance of Leucine and Phenylalanine amino acids as indicators of the disease severity in FRE dogs.

The Use of Ascophyllum nodosum and Bacillus subtilis C-3102 in the Management of Canine Chronic Inflammatory Enteropathy: A Pilot Study.

Simple SummaryThe development of novel, safe and effective therapies is highly desired for managing diseases requiring long-term use of drugs endowed with side effects. In the present investigation, we aimed to assess the impact of gut microbiota modulation strategies, i.e., the brown seaweed Ascophyllum nodosum and/or the probiotic microorganism Bacillus subtilis C-3102, in dogs diagnosed with Canine Chronic Inflammatory Enteropathy. The tested agents were administered on top of a hydrolysed protein diet, in a step-up fashion at 30-day intervals, with faecal collection and clinical evaluation of disease severity being performed before study initiation as well as at the end of each treatment phase. Neither Ascophyllum nodosum, nor its association with Bacillus subtilis C-3102, were able to significantly alleviate clinical signs and augment bacterial richness within the study population. Notwithstanding, increased numbers of beneficial carbohydrate-fermenting bacteria, alongside with higher amounts of faecal acetate were recorded, suggesting a potentially positive effect on gut health.The aim was to assess the effects of Ascophyllum nodosum (AN) with/without Bacillus subtilis C-3102 as alternative treatments for Chronic Inflammatory Enteropathy (CIE) of dogs. Fourteen CIE patients, which had received the same control (CTR) diet, were enrolled to serially receive three diets: (1) hydrolysed protein (HP) diet; (2) 4.0% AN supplemented HP (HPA) food, (3) HPA diet fortified with 125 billion B. subtilis C-3102 spores/10 kg body weight (HPAB diet). Clinical outcome was assessed by Canine Inflammatory Bowel Disease Activity Index (CIBDAI), whereas gut microbiota compositional variations were investigated via 16S rRNA gene analysis, and faecal fermentation end-products by liquid chromatography. Higher abundances of the Ruminococcaceae and Rikenellaceae families were shown in HPA relative to CTR treatment, with Bacillus genus being differentially abundant on HPAB diet. Concentrations of acetate were higher (p < 0.05) in dogs fed HPA compared to CTR diet, and amounts of isovalerate and isobutyrate were greater (p < 0.05) in HPA compared to HP food. A tendency for higher amounts of faecal butyrate was found for the HPAB treatment (p = 0.06). Comprehensively, while displaying potentially positive effects on faecal fermentations, the tested substances failed to improve CIBDAI scores and microbial richness in CIE dogs.

A survey on the prevalence of diarrhea in a Portuguese population of police working dogs

BackgroundDiarrhea is considered the most common clinical sign of chronic gastrointestinal disease in dogs and affects a considerable portion of working and sporting dogs. We aimed to determine the prevalence of diarrhea in police working dogs and evaluate the relationship between feeding, activity level, and animal characteristics with clinical signs. In an observational, prospective study, information on 188 dogs was collected. For each patient, age, sex, breed, specific mission, number of animals at the same housing location, and activity level was recorded. A body condition (BCS) and canine inflammatory bowel disease activity index (CIBDAI) scores were determined, and feces classified according to the Bristol Stool Form Scale. The Kruskal-Wallis test was used to compare recorded data between breeds, mission, age, and sex. Multiple regression was run to predict BCS score, increased defecation frequency, diarrhea, CIBDAI scores, Bristol stool scores, diarrhea from activity level, number of animals at the same housing location, breed, and mission. A p < 0.05 was set.ResultsAnimals in the sample (male n = 96, female n = 92) had a mean age of 5.2 ± 3.2 years and a bodyweight of 24.1 ± 7.2 kg. Four main dog breeds were represented, 80 Belgian Malinois Shepherd Dogs, 52 German Shepherd Dogs, 25 Labrador Retrievers, and 19 Dutch Shepherd Dog. A prevalence of diarrhea of 10.6% was determined, with 4% of dogs having liquid diarrhea. Dogs classified as “extremely active” were more likely to have a low BCS, and the level of activity contributed to diarrhea and BCS prediction.ConclusionPolice working dogs frequently experience diarrhea episodes, which lead to clinical disease and performance loss. Investigation of aetiologies is required.

Hypercoagulability in dogs with chronic enteropathy and association with serum albumin concentration.

BackgroundDogs with protein‐losing enteropathy (PLE) are at risk of developing a hypercoagulable state, but the prevalence of hypercoagulability in dogs with chronic enteropathies (CE) and normal serum albumin concentration is unknown.HypothesisDogs with CE are predisposed to a hypercoagulable state as assessed by thromboelastography (TEG) independent of serum albumin concentration.MethodsDogs with chronic gastrointestinal signs from suspected inflammatory CE between 2017 and 2019 were included. Thirty‐eight were evaluated; every dog had a CBC, serum biochemistry panel, and abdominal imaging performed. The Canine Inflammatory Bowel Disease Activity Index (CIBDAI) was calculated. Thromboelastography was performed at presentation, and reaction time (R), kinetic time (K), α‐angle, maximal amplitude (MA), and global clot strength (G) were recorded. Dogs were considered hypercoagulable if the G value was ≥25% above the reference interval.ResultsSeventeen of 38 (44.7%; 95% confidence interval [CI], 28.6‐61.7%) dogs with CE were hypercoagulable. The G value did not differ between the 19 dogs with normal (≥28 g/L) serum albumin concentrations (9.05 kdyn/cm2; 95% CI, 7.26‐10.84; SD 3.71) and 19 dogs with hypoalbuminemia (11.3 kdyn/cm2; 95% CI, 9.04‐13.6, SD; 4.7; P = .11). The G value was negatively correlated with hematocrit, serum albumin concentration, and duration of signs and positively correlated with age.Conclusions and Clinical ImportanceDogs with CE and normal serum albumin concentration can be hypercoagulable as measured by TEG.

Fecal microbiota transplantation as a new treatment for canine inflammatory bowel disease.

In human medicine, fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection. It has also been tested as a treatment for multiple gastrointestinal diseases, including inflammatory bowel disease (IBD). However, only a few studies have focused on the changes in the microbiome following FMT for canine IBD. Here, we performed FMT in nine dogs with IBD using the fecal matter of healthy dogs and investigated the subsequent changes in the fecal microbiome and clinical signs. In three dogs, the fecal microbiome was examined by 16S rRNA sequencing. Fusobacteria were observed at a low proportion in dogs with IBD. However, the post-FMT microbiome became diverse and showed a significant increase in Fusobacteria proportion. Fusobacterium was detected in the nine dogs by quantitative polymerase chain reaction. The proportion of Fusobacterium in the post-FMT fecal microbiome was significantly increased (p<0.05). The changes in clinical signs (e.g., vomiting, diarrhea, and weight loss) were evaluated according to the canine inflammatory bowel disease activity index. The score of this index significantly decreased in all dogs (p<0.05) with improvements in clinical signs. These improvements were related to the changes in the proportion of microbes, particularly the increase in Fusobacterium. The dogs with IBD showed a lower proportion of Fusobacterium than healthy dogs. This suggests that a low proportion of Fusobacterium is a characteristic feature of canine IBD and that Fusobacterium is involved in this disease. The results of this study may help elucidate the pathogenesis of this disease and its association with Fusobacterium.

Investigation of the efficacy of a dietetic food in the management of chronic enteropathies in dogs

BackgroundChronic enteropathies (CEs) are a common cause of morbidity in dogs. CEs are diagnosed in dogs with chronic gastrointestinal clinical signs (>3 weeks), inflammatory changes on intestinal biopsies and where...

Clonality testing as complementary tool in the assessment of different patient groups with canine chronic enteropathy

Differentiation between canine chronic enteropathy (CCE) and intestinal lymphoma is a diagnostic challenge as histopathology might fail to yield unequivocal results. Detection of clonal rearrangements of the T-cell-receptor gamma (TCRG) chain and IG heavy chain (IGH) V-J genes offer a useful solution. In this retrospective study, histopathology samples of 35 CCE patients and 7 healthy Beagle dogs underwent clonality testing. Patients suffered either from inflammatory bowel disease (IBD), food responsive diarrhea (FRD) or protein loosing enteropathy secondary to IBD (PLE/IBD). Healthy Beagles served as controls (CO).Canine IBD activity index (CIBDAI) and histopathological WSAVA–grading differed significantly (p<0.001) between groups. CIBDAI improved significantly after appropriate therapy (p < 0.0001). Intestinal biopsies of all CO showed polyclonal patterns for B- and T-cell primers. All samples from CCE patients showed polyclonal patterns for the B-cell primers. Targeting TCRG, 4 patients showed a monoclonal or oligoclonal pattern of the lymphocytic infiltrates in the duodenum and/or colon. Clinical improvement was observed in all dogs. Although a small cell lymphoma cannot be excluded in view of the short follow up duration, a false positive result, in the sense of a canonical rearrangement or unspecific amplification due to a antigenic stimulation in a non-neoplastic inflammatory process is possible.

Longitudinal assessment of microbial dysbiosis, fecal unconjugated bile acid concentrations, and disease activity in dogs with steroid-responsive chronic inflammatory enteropathy.

BackgroundMounting evidence from human studies suggests that bile acid dysmetabolism might play a role in various human chronic gastrointestinal diseases. It is unknown whether fecal bile acid dysmetabolism occurs in dogs with chronic inflammatory enteropathy (CE).ObjectiveTo assess microbial dysbiosis, fecal unconjugated bile acids (fUBA), and disease activity in dogs with steroid‐responsive CE.AnimalsTwenty‐four healthy control dogs and 23 dogs with steroid‐responsive CE.MethodsIn this retrospective study, fUBA were measured and analyzed. Fecal microbiota were assessed using a dysbiosis index. The canine inflammatory bowel disease activity index was used to evaluate remission of clinical signs. This was a multi‐institutional study where dogs with steroid‐responsive CE were evaluated over time.ResultsThe dysbiosis index was increased in dogs with CE (median, 2.5; range, −6.2 to 6.5) at baseline compared with healthy dogs (median, −4.5; range, −6.5 to −2.6; P = .002) but did not change in dogs with CE over time. Secondary fUBA were decreased in dogs with CE (median, 29%; range, 1%‐99%) compared with healthy dogs (median, 88%; 4%‐96%; P = .049). The percent of secondary fUBA in dogs with CE increased from baseline values (median, 28%; range, 1%‐99%) after 2‐3 months of treatment (median, 94%; range, 1%‐99%; P = 0.0183).Conclusions and Clinical ImportanceThese findings suggest that corticosteroids regulate fecal bile acids in dogs with CE. Additionally, resolution of clinical activity index in dogs with therapeutically managed CE and bile acid dysmetabolism are likely correlated. However, subclinical disease (i.e., microbial dysbiosis) can persist in dogs with steroid‐responsive CE.

Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease.

Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant ( P < .05) for duodenum ( r = 0.42) and colon ( r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant ( P < .05) correlations were observed for crypt dilation ( r = 0.42), lamina propria (LP) lymphocytes ( r = 0.40), LP neutrophils ( r = 0.45), mucosal fibrosis ( r = 0.47), lacteal dilation ( r = 0.39), and villus stunting ( r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity.

Effect of Enterococcus faecium SF68 on serum cobalamin and folate concentrations in healthy dogs

To study the effect of a 14-day administration of the probiotic Enterococcus faecium SF68 on serum concentrations of cobalamin and folate in healthy dogs. Thirty-six healthy dogs were randomly allocated between probiotic and control groups. Enterococcus faecium SF68 was administered to the probiotic group for 14 days whereas the control group did not receive any product. A blood sample was taken from all dogs when starting the administration (day 1), when the administration ended (day 14) and 14 days later (day 28). Serum cobalamin and folate concentrations and the canine inflammatory bowel disease activity index scores were determined at each time point. There was a progressive reduction of mean serum cobalamin in the probiotic group during the 28-day study, with significantly lower concentration at day 28 compared to baseline and day 14 concentrations. Moderate hypocobalaminaemia was observed in eight dogs at day 28. Probiotic administration was associated with a non-significant increase in mean serum folate concentration at day 14, and a significant decrease at day 28 compared with day 1. The canine inflammatory bowel disease activity index score remained unaltered during the study. Short-term Enterococcus faecium SF68 administration caused a significant reduction of mean cobalamin concentration and moderate hypocobolaminaemia in eight of 18 dogs. Monitoring serum folate appears unnecessary because the probiotic caused a non-significant increase that returned to baseline values after administration was discontinued.

S100A12 concentrations and myeloperoxidase activities are increased in the intestinal mucosa of dogs with chronic enteropathies

BackgroundIntestinal mucosal S100A12 and myeloperoxidase (MPO) are inflammatory biomarkers in humans with inflammatory bowel disease (IBD). However, these biomarkers have not been studied in the intestinal mucosa of dogs with chronic enteropathies (CE), even though dogs with CE have increased S100A12 concentrations in feces and serum. This study investigated mucosal S100A12 concentrations and MPO activities in both dogs with CE and healthy Beagles. ELISA (S100A12 concentrations) and spectrophotometric methods (MPO activity) were used. The associations of both biomarkers with canine IBD activity index (CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations were also investigated. We studied intestinal mucosal samples originating from different intestinal regions of 40 dogs with CE and 18 healthy Beagle dogs (duodenum, ileum, colon, and cecum).ResultsCompared with healthy Beagles, mucosal S100A12 concentrations in dogs with CE were significantly higher in the duodenum (p < 0.0001) and colon (p = 0.0011), but not in the ileum (p = 0.2725) and cecum (p = 0.2194). Mucosal MPO activity of dogs with CE was significantly higher in the duodenum (p < 0.0001), ileum (p = 0.0083), colon (p < 0.0001), and cecum (p = 0.0474). Mucosal S100A12 concentrations in the duodenum were significantly higher if the inflammatory infiltrate consisted mainly of neutrophils (p = 0.0439) or macrophages (p = 0.037). Mucosal S100A12 concentrations also showed a significant association with the severity of total histopathological injury and epithelial injury in the colon (p < 0.05). Mucosal MPO activity showed a significant association (p < 0.05) with the severity of total histopathological injury, epithelial injury, and eosinophil infiltration in the duodenum. There was no significant association of both biomarkers with CIBDAI or clinical outcome.ConclusionsThis study showed that both mucosal S100A12 concentrations and MPO activities are significantly increased in the duodenum and colon of dogs with CE; mucosal MPO was also increased in the ileum and cecum. Future research should focus on assessing the clinical utility of S100A12 and MPO as diagnostic markers in dogs with CE.

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.

Immunohistochemical characterization of gastrointestinal macrophages/phagocytes in dogs with inflammatory bowel disease (IBD) and non-IBD dogs

Intestinal Mϕ play a pivotal role in the maintenance of gut homeostasis, but can also contribute to inflammation such as inflammatory bowel disease (IBD). In contrast to human tissues, little is known about phenotypes of Mϕ in the canine gastrointestinal tract. Therefore, an immunohistochemical study was performed using Abs against Mϕ-associated molecules (Cluster of differentiation (CD)64, CD163, CD204, ionized calcium-binding adaptor molecule 1, L1 Ag, and MHC II) on stomach, duodenum, jejunum, ileum and colon from non-IBD dogs. In addition, marker-expression in the stomach, duodenum and colon of the non-IBD dogs was compared to that in dogs with IBD. Results revealed predominance of resident Mϕ displaying an anti-inflammatory phenotype represented by expression of CD163 as well as CD204 in the gut of non-IBD dogs with high Mϕ numbers especially present in the small intestinal villus area. Compared to non-IBD tissue counterparts, stomach, duodenum, and colon from dogs with IBD showed reduced Mϕ numbers with the exception of slightly increased numbers of CD64+ Mϕ. Correlation analyses between marker-expression of Mϕ and the Canine Inflammatory Bowel Disease Activity Index as well as histological scores failed to reveal relevant relationships. The present study provides evidence of the canine steady state gastrointestinal tract being dominated by Mϕ with anti-inflammatory properties maintaining gut homeostasis. A significant reduction in these resident Mϕ may reflect disturbances in homeostatic capacity that could contribute to the development of canine IBD. In contrast to human IBD and murine disease models, infiltration of pro-inflammatory Mϕ does not significantly contribute to the inflammatory process of canine IBD, which may illustrate possible species-specific differences in IBD pathogenesis.

Effects of a structured exercise programme in sedentary dogs with chronic diarrhoea

The aim of this investigation was to evaluate the effects of a structured exercise programme in sedentary dogs with chronic diarrhoea. Twenty-two dogs were enrolled in the study. All dogs...

Correlation between canine inflammatory bowel disease activity indices after stem cell therapy

DISPARITY between the magnitude of the clinical response, the endoscopic mucosal appearance and the histological reduction of gastrointestinal inflammation after conventional therapy in dogs with inflammatory bowel disease (IBD) is...