Growing evidence suggests that resident E. coli play an important role in the pathogenesis of inflammatory bowel disease (IBD) across species. Among the genes that may contribute to E. coli's role in the development of IBD are those typical of extraintestinal pathogenic E. coli (ExPEC). Here, we tested the hypothesis that mucosal E. coli harboring ExPEC virulence genes may drive inflammation in the small intestine of dogs with lymphoplasmacytic IBD and contribute to a more severe clinical presentation.

A comprehensive investigation of virulence genes in E. coli strains from dogs diagnosed with IBD was performed using a 17-panel multiplex PCR, targeting for 8 genes typical for human IBD-associated adherent and invasive E. coli [Group 1 genes: eaeH, irp2, fimH, ratA, fepC, usp, colV, dsbA] and 9 genes more typically associated with ExPEC [Group 2 genes: cvaC, ompTp, hlyF, etaB, iss, aerJ, ereA, papC] (Johnson TJ J Microbiol. 2008). A cohort of 12 German Shepherd Dogs (GSDs) and 20 non-GSDs diagnosed with lympho-plasmacytic IBD on the basis of clinical signs, intestinal histopathology, and exclusion of other known causes of chronic gastro-intestinal signs was enrolled. E. coli was cultured from endoscopically collected biopsies using MacConkey and sheep blood agar, and identified using API20E (BioMérieux). Statistical analysis was performed using univariate linear mixed effect models and Fisher's exact tests for continuous and categorical variables, respectively. The following dependent variables were considered: i) clinical activity of disease (CCECAI; Allenspach K 2007), ii) histological severity score (WSAVA index; Day M 2008), iii) use of immunosuppressive agents, and iv) euthanasia due to intractable IBD or survival within 1 year after diagnosis. Results revealed that none of the tested virulence factors were significantly associated with the CCECAI index. However, one virulence factor from group 1 [colV:colicin V, antimicrobial peptide; p=0.03) had a significant effect on the WSAVA index. Two of the virulence genes typically associated with ExPEC (Group 2: ompTP: inactivates antimicrobials, and cvaC: secreted toxin resulting in cytolysis) were significantly associated with euthanasia due to intractable IBD (ompTP: OR: 19, cvaC: OR: 30, p=0.05), as well as an increased likelihood of having been treated with immunosuppressives (p=0.03). These data are reminiscent of reports on human ulcerative colitis cases harboring mucosal E. coli with multiple ExPEC virulence factors that were associated with clinical severity. Similarly, our data indicate that specific microbial factors may be important determinants and predictors of disease progression and survival in a sub-group of dogs with IBD.

Disclosures

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