Granulomatous Colitis in Boxers and French Bulldogs

Granulomatous Colitis (GC) is a severe form of inflammatory bowel disease (IBD) seen in Boxers and French Bulldogs, and occasionally other mastiff breeds. Signs include bloody diarrhea, weight loss, anemia, and debilitation. The disease is caused by an aggressive form of E. coli bacteria which invade the intestinal lining and hide within intestinal macrophages – a type of white blood cell. These E. coli are similar to strains known as adherent-invasive E. coli (AIEC) associated with Crohn’s disease in people. Because this is a breed-specific disease in dogs, a heritable abnormality that allows these bacteria to invade and persist in the intestinal lining is suspected. AKC Canine Health Foundation (CHF) funded researchers at Cornell University have been studying this disease to identify the underlying genetic mutations and explore the molecular processes involved. (CHF Grant 02050: Defining the Genetic Susceptibility to Granulomatous Colitis, a Severe Form of Inflammatory Bowel Disease and CHF Grant 01445: Granulomatous Colitis In Boxer Dogs: Genetic Analysis of Disease and Functional Analysis of Bacterial Killing) Results will help develop tools to reduce the incidence of this disease and improve treatment outcomes.

Investigators found a region in the genome of Boxers and French Bulldogs containing mutations associated with the development of GC. The region contains numerous genes comparable to those linked with IBD in humans. Additional study will describe the specific mutations that cause disease risk in dogs and hopefully lead to screening tests to decrease the incidence of this disease.

Since complete elimination of the aggressive E. coli bacteria is required to achieve remission in dogs with GC, investigators also analyzed clinical outcomes to see if susceptibility testing improved response to treatment. Antibiotic susceptibility testing involves growing an infectious agent (such as bacteria or fungus) in the presence of antibiotics. Measuring the bacteria’s ability to grow in such conditions determines the potential effectiveness of each antibiotic tested and shows if the bacteria has developed resistance to any of them.

Results of the case analysis were recently published in the Journal of Veterinary Internal Medicine.¹ They found that two thirds of the E. coli strains cultured were resistant to fluroquinolone antibiotics at the time of initial diagnosis. (Fluroquinolones are a class of antibiotics such as enrofloxacin (Baytril), orbifloxacin (Orbifloxacin), and ciprofloxacin (Cipro) that work by preventing bacterial DNA replication.) Because bacterial infections that are resistant to fluoroquinolone antibiotics are likely resistant to multiple antibiotics and therefore difficult to treat, investigators strongly suggest getting a definitive diagnosis with intestinal biopsy and susceptibility testing before starting antibiotic therapy for colitis. On a positive note, more than 80% of the cases that were treated based on susceptibility testing, even those that were resistant to fluoroquinolones, had a positive long-term clinical response.

These findings provide important clues about the genetic mutations and aggressive bacteria that cause granulomatous colitis in dogs. Similarities between this canine disease and IBD in humans mean that knowledge gained can help both species. CHF and its donors are committed to advancing the health of all dogs and their owners through this One Health approach to scientific discovery. Learn more about our work at akcchf.org/research.

1. Manchester, A. C., Dogan, B., Guo, Y., & Simpson, K. W. (2020). Escherichia coli-associated granulomatous colitis in dogs treated according to antimicrobial susceptibility profiling. Journal of Veterinary Internal Medicine. https://doi.org/10.1111/jvim.15995