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Background: Histopathology is widely used for the diagnosis of inflammatory bowel disease in dogs. Variations in lesions and unavailability of uniform grading systems limit the usefulness of histologic examination. Hypothesis: CD3 cell numbers in chronic enteropathies of dogs correlate with clinical activity of the disease and with severity of histopathologic changes. Animals: Nineteen client-owned dogs examined because of chronic diarrhea, vomiting, or both. Methods: Samples of duodenal and colonic mucosa were collected endoscopically before and after treatment. Dogs that responded to a hypoallergenic diet were grouped as food-responsive diarrhea dogs (FRD, n = 10). Dogs with no clinical improvement after 10 days of treatment then received prednisolone (immunosuppressive doses) and were grouped as steroid-responsive diarrhea dogs (SRD, n = 9). Histopathologic assessment with a standardized grading system was performed retrospectively on the intestinal samples. Histologic score, total number of infiltrating cells, and CD3-positive cells were counted and compared with the clinical scoring. Results: No statistically significant difference was detected among histologic grading, total number of cells in the lamina propria, and T-cell numbers in biopsies before and after treatment in either group (FRD and SRD). Conclusions and Clinical Importance: Currently used histopathologic grading scores, total numbers of cells, and numbers of CD3-positive cells did not allow differentiation between FRD and SRD and did not correlate with clinical response to therapy. Based on these results, new grading scores assessing other criteria than total cell numbers and CD3-positive cells should be evaluated in the future. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and commensal microflora. Toll-like receptors (TLRs) recognize microbe-associated molecular patterns (MAMPs), but their role in enteropathies in dogs is unknown. Hypothesis: That there is a dysregulation of TLRs recognizing bacterial MAMPs in dogs with IBD. Animals: Sixteen healthy beagles and 12 dogs with steroid-treated (ST) and 23 dogs with food-responsive (FR) diarrhea. Methods: Prospective, observational study. mRNA expression of canine TLR2, 4, and 9 was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies obtained before and after standard therapy. Samples from control dogs were taken at necropsy, with additional biopsies of stomach, jejunum, ileum, and mesenteric lymph node in 6 dogs. Results: There were significant differences ( P≤ .017) in expression of TLR2, 4, and 9 between the 6 sampled locations in healthy control dogs (lymph node > small intestine ≥ colon). Before therapy, ST expressed more mRNA than control dogs for all 3 receptors ( P < .05). There were no significant differences between pretreatment and posttreatment values, even though 32/35 dogs improved clinically. No associations were found when comparing receptor mRNA expression with either histology or clinical activity scores. Conclusions and Clinical Importance: Bacteria-responsive TLR2, 4, and 9 are upregulated in duodenal and colonic mucosa in IBD. This might lead to increased inflammation through interaction with the commensal flora. The absence of significant changes after therapy despite clinical improvement might point toward the existence of a genetic predisposition to IBD as described in human IBD. [ABSTRACT FROM AUTHOR]

Repair processes of the inflamed intestine are very important for dissolution of chronic enteropathies (CE). Therefore, we examined the mRNA abundance of growth hormone receptor (GHR), insulin-like growth factors (IGF)-1 and -2 in duodenal and colonic biopsies of dogs with CE such as food-responsive diarrhoea (FRD) and inflammatory bowel disease (IBD) before and after treatment as compared with each other and healthy dogs. A clinical score (Canine IBD Activity Index = CIBDAI) was applied to judge the severity of CE. Biopsies of duodenum and colon from client-owned dogs with CE were sampled before (FRD(bef), n = 5; IBD(bef), n = 5) and after treatment (FRD(aft), n = 5; IBD(aft), n = 5). Intestinal control samples were available from a homogenous control population (n = 15; C). Intestinal samples were homogenized, total RNA was extracted, reverse transcribed and analysed by real-time polymerase chain reaction to measure mRNA levels of GHR, IGF-1 and IGF-2. Results were normalized with glyceraldehyde phosphate dehydrogenase as housekeeping gene. The CIBDAI decreased during the treatment period in FRD and IBD (P < 0.01). In duodenum, GHR mRNA levels were higher in all groups than in C (P < 0.001). Duodenal IGF-1 mRNA levels in FRD(aft) and IBD(aft) tended to be higher than in C (P < 0.1). The IGF-2 mRNA abundance in FRD(aft) was higher than in C (P < 0.05) in duodenum. In colon, mRNA levels of IGF-1 in IBD(aft) were higher than in FRD(aft) (P < 0.05) and levels differed between IBD(aft) and C (P < 0.05). In conclusion, mRNA levels of GHR, IGF-1 and IGF-2 in the gastrointestinal tract were increased during CE when compared with gastrointestinally healthy dogs. The data suggest that GHR, IGF-1 and IGF-2 are involved in gastrointestinal repair processes.

The mammalian gastrointestinal tract is a complex consisting of the intestinal epithelial cells, the mucosal immune cells and the endogenous microflora. Since a couple of years, probiotics are used in animal production to improve performance. But there are only few results available on the immune modulating effects of pro- and prebiotics in human and veterinary medicine. Recent studies are promising that pro- and prebiotics can be used as an alternative to conventional therapy with immune suppressive drugs in patients with inflammatory bowel disease or dietary hypersensitivity. Yet further randomized and placebo-controlled studies are needed to clarify these mechanisms in vivo.

Concentrations of nonnutritional factors, such as insulin-like growth factor-I (IGF-I), in bovine colostrum are high and can modulate neonatal gastrointestinal tract development and function. In neonatal calves, we have investigated effects on intestinal epithelial cell morphology, proliferation, and absorption of feeding milk-born human IGF-I (hIGF-I) or a bovine colostrum extract. Calves were fed a milk-based formula containing amounts of nutrients comparable to colostrum for the first 3 d and a milk replacer from d 4 on. Formula and milk replacer contained only traces of nonnutritional factors. In experiment 1, supraphysiological amounts of hIGF-I (3.8 mg/L formula; secreted by transgenic rabbits with their milk) were added to the formula. Xylose appearance in blood (after feeding xylose on d 5) and intestinal traits (after euthanasia on d 8) did not differ between groups. In experiment 2, an extract of first-milked bovine colostrum that provided physiological amounts of IGF-I (0.50, 0.15, and 0.09 mg of IGF-I/L formula on d 1, 2, and 3, respectively, and 0.09 mg of IGF-I/L milk replacer on d 4) was added to formula or milk replacer. Plasma xylose concentration in the control group was transiently higher than in calves fed the colostrum extract. On d 5 (after euthanasia), villus circumferences and heights in small intestine, and epithelial cell proliferation rate in intestine were higher in calves fed the colostrum extract than in controls. In conclusion, orally administered hIGF-I from transgenic rabbits had no effect on the intestinal tract. However, feeding a bovine colostrum extract enhanced intestinal villus size, although it appeared to transiently decrease the absorptive capacity.