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.

Chronic diarrhoea is a frequent complaint in canine practice and the diagnostic path is often characterised by numerous diagnostic tests and stepwise empirical treatments, often applied before gastrointestinal endoscopy/mucosal biopsies. These include dietary interventions (novel protein, hydrolysed protein diet), parasiticides and still, in many cases, antibacterials. Indiscriminate use of antibacterial drugs risks detrimental consequences for both the individual patient (antimicrobial resistance, long‐term disruption of intestinal bacterial populations, potential worsening of gastrointestinal signs) and the general public. For that reason, in this Perspective essay we advocate use of antibacterials only after histopathologic evaluation of gastrointestinal biopsies or, for those cases in which endoscopy is not possible, after other therapeutic trials, such as diet/pre‐probiotics or anti‐inflammatory drugs have proven unsuccessful. They should be reserved, after appropriate dietary trials, for those canine chronic diarrhoeic patients with signs of true primary infection (i.e. signs of systemic inflammatory response syndrome or evidence of adherent‐invasive bacteria) that justify antibacterial use.

Dysbiosis and perturbations of fecal metabolic profiles have been reported in dogs with inflammatory bowel disease. Currently the incidence of dysbiosis and the fecal metabolomic profile in Yorkshire Terriers with chronic enteropathy (YTE) and the effects of treatment are unknown. This prospective observational study analyzed the dysbiosis index (DI) and fecal bile acid, sterol and fatty acid profiles in 14 Yorkshire Terriers with active YTE, 11 dogs in clinical remission, and 26 healthy Yorkshire Terriers. YTE was associated with dysbiosis and a significant increase in fatty acids (docosanoate, p = 0.002; gondoate, p = 0.026; erucate, p < 0.001; nervonate, p < 0.001; linolenate, p < 0.001), and plant sterols (campesterol, p < 0.001; brassicasterol, p = 0.024). The abundances of Fusobacterium (p < 0.001) and Cl. hiranonis (p = 0.018) and the concentrations of the secondary bile acid ursodeoxycholic acid (p = 0.033) and the plant sterol sitostanol (p = 0.003) were significantly decreased compared to healthy dogs. Dysbiosis, abundances of Fusobacterium, Cl. hiranonis and fecal concentrations of bile acids and sterols did not recover after treatment, while fecal fatty acid concentrations decreased in treated dogs. YTE is associated with dysbiosis and changes in bile acid, fatty acid, and sterol metabolism. These changes only recovered partially despite clinical remission. They might be breed-specific and involved in the pathogenesis of YTE.