Understanding the role of diet and enteric bacteria in the development of feline diarrhea (Sponsored by Nestle Purina)
Feline inflammatory bowel disease (IBD) applies to a number of poorly understood enteropathies characterized by the infiltration of inflammatory cells into the gastrointestinal (GI) mucosa. The cellular infiltrate is composed of variable populations of lymphocytes, plasma cells, eosinophils, and neutrophils that can be distributed throughout the GI tract.1-3 In severely affected cats, this infiltrate may be accompanied by changes in the mucosal architecture, including villus atrophy, fusion, fibrosis, and lymphangiectasia.
Although IBD appears to be a common clinical problem in cats, little is known about the etiopathogenesis or the local and systemic consequences of the disease, including the development of lymphoma and nutritional deficiencies.4 In addition, the nature of inflammation associated with IBD is just beginning to be characterized beyond the visible changes in gross histopathology that have been described.5-11
Feline IBD is characterized by persistent clinical signs consistent with GI disease (e.g. vomiting, anorexia, weight loss, diarrhea) that occur concurrently with histologic evidence of mucosal inflammation.12 Many cats with IBD have concurrent inflammation of the liver and pancreas—a phenomenon called triaditis.13 The median age of cats presenting with IBD is around 7 years, and most cats present with a history of these signs occurring intermittently for weeks to years. Purebred cats, such as the Siamese and Abyssinian, may be overrepresented, but definitive breed predilections have not been reported. There is no reported predilection based on sex.This paper reviews what is known about feline IBD, with particular focus on the role of commensal and pathogenic intestinal bacteria as well as diet in the management of the disease.
The role of bacteria
In humans and experimental animals, recent studies indicate a strong association between the development of IBD and a breakdown of normal tolerance mechanisms, host susceptibility, and enteric microflora.14-17 It is likely that these same factors are important in feline IBD. (See "Are Bacteria a Key Component?" on page 4) It is clear that modulation of the enteric microenvironment in humans with IBD has been shown to reduce proinflammatory cytokines in the mucosa and, therefore, decrease the inflammatory response.18 In humans, IBD therapy has included antibiotics with immune-modulating capacity, prebiotics, probiotics, and immunosuppressants as well as other drugs that modify cytokine release.17,19
Unfortunately, studies assessing modulation of enteric flora (using probiotics, prebiotics, or other specific therapy for cytokines) in cats with IBD are only in the early stages. Nevertheless, few studies have shown that intestinal microbiota in cats with IBD are clearly different from those in normal cats and often the difference is a decrease in normal commensals (e.g. bifidobacteria, lactobacilli) and an increase in pathogenic species.6,9 At this time, therapy for IBD in cats continues to include inflammatory suppression and antibiotic therapy. The most effective IBD therapies include corticosteroids (i.e. prednisolone or methylprednisolone, 1 to 2 mg/kg PO Q 12 H) or other drugs that interrupt the proinflammatory pathways active in the gut. In cats that are intolerant of corticosteroids, budesonide therapy may be a reasonable choice.
Alternatively, in cats in which corticosteroids are no longer effective or are causing morbidity (e.g. diabetes), immunosuppressive therapy may be necessary and is often effective. The two drugs most commonly recommended and effective for cats in this setting are cyclosporine and chlorambucil.
Antibiotic therapy with 5 to 10 mg/kg PO Q 12 H of metronidazole has been effective for a number of years and continues to be recommended as initial therapy for IBD.12,20 There is also a widely held belief that metronidazole is effective not only because of its antibacterial properties but because of concurrent immune-modulating properties. Some data support these ideas, but the specific role of metronidazole as treatment for IBD is still not completely known. Because metronidazole may be poorly tolerated and has potential for serious adverse effects, it should not be given indefinitely. Another antibiotic that may be useful in cats with presumed IBD is tylosin at a dose of 10 to 20 mg/kg PO Q 12 H; however, less is known about the effects of tylosin in cats when used long-term.21,22
Finally, data in humans with IBD are increasingly showing that probiotics and antioxidant prebiotic nutraceuticals may be important components of therapy.19 At this time, it is difficult to make specific recommendations concerning the probiotic or nutraceutical therapy with the greatest benefit because of the paucity of studies in cats with IBD and the species-specific nature of probiotics and their effects. However, probiotics that provide an immune-modulating effect or that increase the number of beneficial species while competing against pathogens might be expected to be helpful. In several studies in kittens, probiotics containing Enterococcus faecium (SF68) appeared to improve immune function and had better responses to therapy when exposed to enteric protozoa.23 Furthermore, whereas probiotic therapy alone would not be expected to produce clinical remission, cats undergoing long-term therapy for IBD may benefit from the addition of probiotics to their treatment regimen.