CURRENT AND EMERGING OPTIONS FOR IBD THERAPY
Albert E. Jergens, College of Veterinary Medicine, Iowa State University, Ames, IA, USA,
ajergens@iastate.edu
INTRODUCTION
Arguably, idiopathic inflammatory bowel disease is the most common histologic diagnosis in
dogs and cats with histories of chronic vomiting and diarrhea. Uncontrolled studies and
anecdotal reports from many clinicians and medical centers report a favorable response of IBD
to several different forms of medical therapy. Unfortunately, the efficacy of these different forms
of therapy has not been rigorously validated by randomized, controlled clinical trials.1 Evidencebased observations clearly imply a positive role for elimination dietary therapy of IBD alone or in
combination with drug therapy; however, these data are limited. Non-traditional therapies
including pre-/probiotic therapy for canine and feline IBD are in their infancy and have yet to be
reported. Root causes for many of the deficiencies in our knowledge base of IBD therapy
include poorly defined histopathologic criteria for IBD diagnosis and an absence of indices for
defining clinical disease severity and the effect of therapy.2 This presentation will review current
treatment strategies in human IBD, summarize drug/dietary therapies for canine and feline IBD,
and review emerging therapies including the use of probiotics/prebiotics in experimental and
companion animal IBD.
MEDICAL THERAPY FOR HUMAN IBD
The human inflammatory bowel diseases (ulcerative colitis [UC] and Crohn’s disease [CD]) are
complicated disease entities with a myriad of treatment options. Clinical studies must evaluate
treatment strategies for UC versus CD; different stages of disease – induction vs. maintenance
therapy and treatment of active vs. quiescent disease; single vs. multi-organ involvement; and
disease flares. The treatment pyramid for UC includes 5-aminosalicylates (5-ASA, most
effective as a topical agent) and steroids as mainstays of therapy.3 For more severe disease,
cyclosporine has become an accepted addition to the pharmacologic armamentarium.4
Immunosuppression with azathioprine (AZA) or 6-mercaptopurine (6-MP) is quite effective in
maintaining steroid-induced remission. There remains insufficient clinical evidence supporting
the use of antibiotics or unique biologics (e.g., infliximab) in routine therapy of UC. Nutritional
therapy for UC is indicated in patients with specific nutritional deficiencies or gross malnutrition.
Considerably more clinical trial information is known concerning therapy for CD. Broadly,
humans with mild-to-moderately active disease are treated in a step-wise fashion with oral
mesalamine or sulfasalazine, adding antibiotics such as metronidazole or ciprofloxacin, then
progressing to budesonide, and finally using oral corticosteroids in patients who fail to respond
to initial first-line therapies.5 Budesonide is more useful with CD involving the ileum. AZA and
6-MP are indicated in steroid-dependent patients in an attempt to taper or withdraw steroids.
Infliximab is used in patients with CD who do not achieve adequate clinical response despite
treatment with conventional therapies. There is surprisingly little evidence for the use of
elimination diets in CD as compared to their use in canine and feline IBD. Omega-3 fatty acids
have been investigated in CD and UC with controversial results. Several studies have
investigated probiotics (e.g., E. coli, Nissile, VSL#3) in human IBD where they have shown
efficacy in the maintenance of UC and chronic pouchitis, respectively.6
PHARMACOLOGIC THERAPY FOR CANINE AND FELINE IBD
Management of IBD varies widely between clinicians. Well designed therapeutic trials have not
been performed, and therapy remains largely empirical, being influenced by the rapidity of
clinical remission, the severity of adverse effects, the acceptability by patients and clients, and
drug costs. Corticosteroids (e.g., prednisone, prednisolone) are potent, rapidly acting oral or
topical medications used as first-line therapy for canine and feline IBD. Budesonide is a poorly
absorbed corticosteroid with limited bioavailability due to extensive first-pass metabolism
(degraded by the liver) that may produce therapeutic benefit with reduced systemic toxicity.
AZA and 6-MP are chemically-related immunomodulators. Their onset of full activity is slow and
they may be associated with significant side effects (bone marrow toxicosis, hepatopathy) with
chronic use. Oral cyclosporine inhibits T cell proliferation and has a rapid onset of action;
however potential toxicity may limit its routine use. Salicylates, such as sulfasalazine, may be
useful in cases of IBD colitis where the active moiety (5-ASA = mesalamine) provides topical
anti-inflammatory actions. Antibiotics (metronidazole, tylosin) are widely prescribed for small
and large intestinal IBD although there is little substantive clinical data supporting their use.
Their mechanisms of action are unknown but may include modulation of resident microflora.

Uncontrolled clinical trials attest to the fact that corticosteroids, used as a single agent or
in combination with other medications, are effective in acute therapy of canine and feline
IBD.1

One randomized controlled clinical trial of dogs having moderate-to-severe IBD showed
that clinical remission rates, CIBDAI scores, and serum [CRP] were identical in dogs
treated with prednisone alone versus dogs treated with a combination of prednisone and
metronidazole.7

AZA/6-MP are predominantly used as a component of maintenance therapy to lower
glucocorticoid doses. No data exists on controlled trials in the dog or cat.

Oral cyclosporine @ 5mg/kg PO q 24 h has been reported in one small clinical trial to be
useful in dogs with steroid-refractory IBD.8

Metronidazole has been reported to be effective as a single agent for mild feline IBD.9
Tylosin has been reported to be beneficial in dogs with chronic colitis.10

Enrofloxacin combined with other antimicrobials ameliorates clinical signs and histologic
lesions in dogs with histiocytic ulcerative colitis.11
NUTRITIONAL THERAPY FOR CANINE AND FELINE IBD
There is limited but good evidence-based data to support an important role for nutritional
therapy in dogs and cats with IBD. Unfortunately, there are very few clinical trials where dietary
treatments are compared to each other and to a control group (randomized, double-blind trials,
etc). The use of moderately fermentable fiber supplements (psyllium, beet pulp) improves
clinical signs in dogs and cats with IBD colitis. Potential mechanisms for these observations are
numerous and may include binding of colonic irritants, normalization of dysmotility patterns,
enhanced production of beneficial SCFA, and “prebiotic” restoration of normal microflora.
Elimination dietary trials are beneficial in dogs and cats with chronic enteropathies (including
IBD), and further serve to rule-out food-responsive causes for GIT signs. The optimal novel
protein component and duration of feeding for control of clinical signs is debatable.

Uncontrolled clinical trials attest to the fact that novel protein sources are beneficial in
the treatment of canine/feline IBD. Additionally, these diets should be highly digestible,
gluten-free, and nutritionally complete for long-term use.1

30% of cats with chronic GI signs were reported to have dietary sensitivity.12

Resolution or attenuation of clinical signs was observed in cats with lymphocyticplasmacytic colitis that were treated with fiber supplementation.13

In a separate study, 26/27 dogs having idiopathic colitis responded to a high fiber diet.14
PREBIOTICS AND PROBIOTICS IN INFLAMMATORY BOWEL DISEASE
There is very little clinical data evaluating the use of probiotics to treat diarrheal disease in dogs
or cats. Probiotic bacteria may reduce intestinal inflammation by diverse mechanisms including
improved barrier function, modulation of the intestinal immune system, production of
antimicrobials, and alteration of the intestinal microflora. Microencapsulated Enterococcus
faecium SF68 strain is now commercially available as a dietary supplement (FortiFlora, Nestle
Purina) for both dogs and cats. Clinical studies evaluating its use as a primary or adjunctive
therapy for IBD have not been published to the author’s knowledge. Lastly, the addition of
prebiotics such as fructooligosaccharides (FOS) for therapy of IBD has not been shown to be
beneficial to date. The author is unaware of any dietary trials evaluating the effects of prebiotics
in IBD.

A probiotic cocktail was shown to reduce clinical severity (CIBDAI) and alter luminal
floral numbers in a prospective, placebo-controlled trial in dogs with food-responsive
diarrhea treated with an elimination diet.15

Using an ex vivo culture system derived from endoscopic biopsies, a probiotic cocktail
was effective in reducing pro-inflammatory cytokine proteins and their expression in
dogs with mild chronic enteropathy.16

Dietary FOS was shown to minimally impact beneficial fecal flora of healthy Beagles.17

Supplementation of the diet with FOS resulted in some alteration of the fecal flora of
normal cats. Compared with samples from cats fed a basal diet, there was a trend
for some beneficial bacteria to be increased after FOS supplementation although there
was no change in total bacterial counts between diets.18
SUMMARY AND CONCLUSIONS
Although there is evidence-based data to support the use of elimination diets, corticosteroids,
immunomodulators, and some antibiotics in the treatment of dogs and cats with IBD, there are
many aspects of therapy with these agents for which the data are lacking or inadequate.
Additional prospective data are needed to resolve the areas of controversy. That said, further
refinement in diagnosis of the “IBD syndrome” via improved histopathological criteria and use of
robust clinical indices for assessment of disease activity will strengthen our understanding of
how these therapies might provide optimal care to our patients.
REFERENCES
1. Jergens AE. Vet Clin North Am: Small Anim Pract 1999; 29:501-521; 2. Jergens AE, et al. J
Vet Intern Med 2003; 17:291-297; 3. Sutherland L, et al. Cochrane Database Systemic Rev
2005: issue 2; 4. Loftus CG, et al. Gut 2003; 52:172-173; 5. Sandborn WJ. Medical therapy for
Crohn’s disease. In: Kirchner’s Inflammatory Bowel Diseases. Sartor and Sanborn (eds), 2004
pp 531-554; 6. Ewaschuk JB, Dieleman LA. World J Gastroenterol 2006; 12:5941-5950; 7.
Jergens AE, et al. J Vet Intern Med 2004; 18:424; 8. Allenspach K, et al. J Vet Intern Med 2006;
20:239-244; 9. Jergens AE. Comp Cont Educ Pract Vet 1992; 14:509-518; 10. Westermarck E,
et al. J Vet Intern Med 2005; 19:177-186; 11. Hostutler AR, et al. J Vet Intern Med 2004;
18:499-504; 12. Guilford WG, et al. J Vet Intern Med 2001; 15:7-13; 13. Dennis JS, et al. J Am
Vet Med Assoc 1993; 202:313-318; 14. Nelson RW, et al. J Vet Intern Med 1998; 2:133-137; 15.
Sauter SN, et al. J Anim Physiol Anim Nutr (Berl) 2006; 90:269-277; 16. Sauter SN, et al.
Domest Anim Endocrinol 2005; 29:605-622; 17. Willard MD, et al. Am J Vet Res 2000; 61:820825; 18. Sparkes AH, et al. Am J Vet Res 1998; 59:436-440.