Introduction to IBD and Medical Management

Canine and feline inflammatory bowel disease (IBD) has been described as an idiopathic intestinal disorder characterized by chronic or recurrent gastrointestinal signs as well as the presence of inflammatory cells/markers in the intestinal tissue; however, the undiscriminating use of the term IBD in veterinary medicine (and the lack of a universally recognized diagnosing/scoring system of chronic inflammatory disorders) has led to some confusion on what exactly IBD represents when evaluating our small animal patients.

Recent scientific publications have further described that IBD not only encompasses a diverse group of idiopathic, chronic gastrointestinal disorders, but also emphasized the vital role of the relationship between the intestinal microbiotia and the host immune system, which are both crucial elements for disease development.

Main chief clinical signs comprise diarrhea, vomiting, weight loss, and in most cases, the presences of histopathological lesions of inflammation. Treatment of IBD involves pharmacological and dietary interventions; in addition, exogenous manipulation of the intestinal microbiota using prebiotic molecules and probiotics.

Current medical treatment options to manage the different types of IBD include:

A.  Antibiotics - although many clinicians may justify its use, antibiotic therapy has not been systematically studied in a large number of IBD patients. Common antibiotics reported include metronidazole, oxytetracycline, ciprofloxacin and tylosin. The use of tylosin in dogs with antibiotic responsive diarrhea has been documented in a number of cases; however, diarrhea may recur in the absence of continuous tylosin therapy. Granulomatous colitis of Boxers and some other breeds is usually treated with enrofloxacin.

B.  Drugs used to suppress the immune system of the host.

a.  Glucocorticoids used on dogs and cats with IBD are mainly prednisone and prednisolone. Dexamethasone should be avoided due to its down-regulatory effects in the expression of enzymes at the brush border level. Formulations of a delayed-release steroid (budesonide) have been effective in the treatment of human IBD. Still, there is limited available information on the use of this drug in dogs and cats with IBD.

b.  Cytotoxic drugs most of the time are reserved for patients unresponsive to prednisolone (and dietary) therapy. Azothioprine may be the second line of therapy in dogs with IBD (not recommended in for cats due to its toxic effects). Chlorambucil is a good therapeutic substitute for cats unresponsive to (or in addition to) glucocorticoids.

c.  Other immunosuppressive drugs which have been used in veterinary medicine include: methotrexate, cyclophosphamide, cyclosporine, and tacrolimus; however, relevant scientific information is still insufficient, limiting the clinical use of these drugs.

Dietary Management of IBD (Chronic Enteritis) in Dogs and Cats

Nutrition is pivotal in the management of gastrointestinal (GI) disease and many cases are managed by dietary therapy alone. Diet has a direct effect on intestinal physiology, motility, cell renewal rate, microbiome, enzyme production, ammonia production, and volatile fatty acid content. Since most GI diseases are influenced by diet, it is vital to perform a good nutritional assessment including a complete diet history. The World Small Animal Veterinary Association's Global Nutrition Committee (WSAVA GNC) has developed guidelines for nutritional assessment.

Dietary management has become included in the first line of treatment for chronic enteritis; many clinicians start with a diet trial with a hydrolysed protein diet or a novel protein diet. However, without sufficient discussion about diet, owners may undermine the effect of the diet trial with treats, snacks and food used to give medication. The use of hydrolyzed diets may have an advantage over novel protein diets as the diet history may not always be complete. Response to dietary therapy with hydrolysed diets for chronic enteritis is about 60%. Controlled studies of human patients receiving exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD, which may also support the concept of using hydrolysed diets.

It should be noted that while highly digestible diets may be appropriate for acute diarrhea, they may not be appropriate for the chronic diarrhea of IBD as they often contain multiple protein sources.

Dietary Fat

Low fat diets are often recommended for pets with GI disease, although in healthy dogs and cats fat is highly digestible. If a pet has steatorrhea or lymphangectasia, the dietary fat should be restricted. In dogs with lymphangectasia, 79% responded to dietary fat restriction with a significant decrease in clinical activity and an increase in albumin, total protein, and blood urea nitrogen concentrations.

In humans, high consumption of linoleic acid (an omega-6 PUFA), such as in red meat and some cooking oils, is associated with a higher incidence of Crohn's disease (a human form of IBD). People who consumed higher levels of the omega-3 PUFA docosahexanoic acid were less likely to be diagnosed with it. In mice with the equivalent of Crohns disease, feeding an omega-3 fat-rich diets for 16 weeks significantly ameliorated the inflammation of the terminal ileum.

No dietary risk factor studies have been published for IBD in dogs or cats and the IBD of humans does differ from that of dogs and cats; however, markers of inflammation in other organ systems do increase with saturated fat or omega 6 fatty acids consumption. Therefore, a decrease in these dietary fats is a reasonable approach.

High-Fiber Diets

High-fiber diets may be helpful in pets with large bowel diarrhea. Insoluble fiber increases fecal bulk, improves colonic motility, and binds nonabsorbed fluid in the intestinal lumen. Soluble fiber binds nonabsorbed fluid into gels and functions as a prebiotic to potentially increase the concentrations of beneficial bacteria. Soluble fiber is fermented by intestinal bacteria into short-chain fatty acids, including butyrate, which is the preferred energy source for colonocytes. Studies in humans have reported that IBD is associated with impairment in short-chain fatty acid (SCFA) production, mainly acetate, propionate, and butyrate. Therefore, it is reasonable to consider therapeutic approaches that increase colonic SCFA production for colitis cases. Fermentation also decreases intestinal intraluminal pH inhibiting opportunistic pathogens such as Clostridium and Salmonella species. Most high-fiber diets contain both soluble and insoluble forms to provide the benefits of both.

The Microbiome and Probiotics

The microbiome is the genetic mass of microorganisms and their environment occurring is various body areas. The GI microbiome is thought to be disturbed in inflammatory bowel disease (IBD), a situation termed dysbiosis. Commonly identified microbiome changes in IBD are decreases in bacterial groups within the phyla Firmicutes and Bacteroidetes, and increases within Proteobacteia. Furthermore, there is a reduction in the diversity of Clostridium clusters XIVa and IV, suggesting these bacterial groups may have a role in maintaining GI health. The bacterial changes are likely associated with altered microbiota metabolic functions (e.g., decreased short chain fatty acids, altered amino acid metabolism, changes in redox equilibrium, and altered bile acid metabolism) which may exacerbate the inflammatory state.

In dogs with food responsive diarrhoea a probiotic cocktail had beneficial effects on intestinal cytokines and microbiota, although the signs had improved with the diet alone. Duodenal Il-10 mRNA levels decreased and colonic interferon-gamma mRNA levels increased. While cytokine patterns changed in vitro in response to probiotic treatment, the changes were not significantly associated with the clinical response.

A synbiotic (probiotic plus prebiotic) study on the GI microbiome of healthy dogs and cats showed little change in the predominant bacterial phyla present in faeces although there was an increased abundance of the probiotic bacteria in the faeces (Garcia-M, et al. 2011). The intestinal microbiome generally reverts back to the population present prior to probiotic supplementation shortly after the probiotic is stopped.

The combination probiotic, VSL#3, restores the expression tight junction components (claudin-2, occludin, and adherens junction proteins) in the intestine in dogs with IBD (Rossi, et al. 2013). Another study on the effects of VSL#3 compared to treatment with prednisolone and metronidazole in twenty dogs IBD showed a significant decrease in clinical and histological scores with both treatments; however, treatment with the probiotic increased regulatory T-cell markers (TGF-ß+ and FoxP3+). The dogs treated with probiotics also had a normalization of the microbiome dysbiosis.

References

References are available on request.