MORE than 75 people from 17 countries in Europe attended a recent symposium in Lausanne, Switzerland, to hear presentations on gastrointestinal immunopathology from six experts in the subject. The meeting was hosted by Nestlé Purina.
Among the topics discussed were dietary modulation of inflammatory bowel disease (IBD) in pets and Crohn’s disease in humans, the essential role of intestinal flora in these diseases and recent clinical findings using probiotics in GI disease.
Delegates had the opportunity to visit the Nestlé Research Center laboratories where new technologies, such as “metabonomics” and “nutrigenomics”, are being used to identify specific biological pathways and nutritional findings that can be applied in both people and pets.
Professor Stan Marks from the University of California, Davis, reviewed the latest approaches to modulating intestinal mucosal integrity using effective dietary interventions such as protein hydrolysed diets, prebiotics and probiotics.
Professor Frédéric Gaschen from Louisiana State University explained the importance of defining the phenotype in chronic enteropathies in canines in order to offer the most appropriate treatment.
Professor Kenny Simpson from Cornell University (a graduate of the Edinburgh veterinary school) presented his research results and an overview of the relationship between mucosal bacteria and IBD in dogs.
Dr Eduardo Schiffrin from Nestlé Clinical Nutrition, discussed effective nutritional solutions for human patients suffering from Crohn’s disease, using state-of-the-art food products containing TGF-ß.
Dr Jalil Benyacoub, head of the immunology group in the Nutrition and Health Department at Nestlé, shared the latest information regarding the health benefits of feeding probiotics in humans and the perspectives for pets; and Professor Mike Lappin revealed the results of recent studies on the use of probiotics in a clinical setting performed by his group at Colorado State University.
These investigations revealed that supplementation with Enterococcus faecium SF68 (the probiotic bacterium in Nestlé Purina’s FortiFlora) has an immunomodulating effect which can have clinical benefits in gastrointestinal and other diseases.
Studies on probiotics
Prof. Lappin said there had been many studies of the effects of probiotics on the health of people, but very few in small animals. His laboratory team, along with others, had recently carried out studies in both dogs and cats on the effects of E. faecium SF68.
In one study E. faecium SF68 supplementation was found to have an immunomodulating effect in healthy puppies and kittens following vaccination – for canine distemper virus and feline herpes virus type 1 (FHV- 1), feline calicivirus and feline panleukopaenia virus respectively – that might have clinical benefit for a variety of disease syndromes of the GI or other systems.
In a further study of adult cats with chronic FHV- 1 infection subjected to repeated mild stress (rehousing), supplementation with the probiotic resulted in greater faecal microbial diversity, indicating a more stable microbiome which could be significant in the management of stress diarrhoea, and fewer episodes of conjunctivitis, suggesting that administration of the probiotic lessened morbidity from chronic FHV- 1 infection.
Using the hypothesis that cats and dogs housed in an animal shelter and fed a diet containing E. faecium SF68 would have fewer episodes of diarrhoea and improved faecal scores compared to untreated dogs and cats, a further study was performed.
Diarrhoea prevalence rates were low for all dogs so statistical differences were not detected in dogs but the percentage of cats with diarrhoea of two days or more was significantly elevated in the untreated group, suggesting, said Prof. Lappin, that administration of the probiotic to cats housed in shelters may reduce the number of days with diarrhoea.
In summary, he said, controlled studies evaluating the use of probiotics in dogs and cats are limited but there is evidence that E. faecium SF68 is well tolerated and may have various clinical applications.
What is IBD?
Prof. Marks described IBD as a complex and heterogeneic disorder due to individual genetic variations, environmental influences, and alterations in the intestinal microflora.
Modulation of the intestinal microflora and intestinal mucosal barrier via nutritional intervention appeared to play an important role in the prevention and management of IBD, he said.
A variety of dietary components can modulate the integrity of the intestinal mucosa. Elimination or protein hydrolysate diets are commonly recommended for IBD because, regardless of the underlying aetiology for any given patient, exaggerated responses to dietary antigens are often suspected in patients with IBD.
It is also increasingly clear that dietary influences on the intestinal flora are involved in health and disease. Among the nutritional approaches to promote gastrointestinal tract health, prebiotics and probiotics have gained a strong interest in recent years.
Glutamine is used as a significant fuel source by mucosal leukocytes (especially lymphocytes) and small intestinal epithelial cells. Enteral glutamine supplementation is probably beneficial in critically ill animals but whether there is any benefit in supplementing normal enteral diets is uncertain.
Prof. Marks said that glutamine was given in a huge range of doses but no one really knew why.
Antioxidants are commonly recommended for dogs and cats with IBD to counter the oxidative stress which undoubtedly occurs in these patients. However, dogs and cats do not exhibit large numbers of the major oxidant producing species (neutrophils and macrophages) compared to humans, and therefore antioxidant supplementation, although recommended, may be less beneficial in small animals than in humans.
Arginine supplementation in order to modulate nitric oxide (NO) production within the mucosa is controversial, he said, adding that further research was needed before its use (or those of iNOS inhibitors or even NO donors or precursors) could be recommended therapeutically.
Dietary fat restriction is vital in dogs diagnosed with lymphangiectasia but is more controversial in other conditions as fat increases palatability and is a valuable source of calories. The ability of dietary polyunsaturated n-3 fatty acids to compete with arachidonic acid for oxygenation by cyclooxygenase and lipoxygenase is well known but there are no reports in the veterinary literature demonstrating the efficacy of n-3 fatty acid supplementation in managing canine or feline IBD. Again, more research is needed, Prof. Marks said.
Nutritional derangements are also a feature of IBD. The disruptions of absorptive area, normal epithelial function, permeability and motility that occur with IBD result in disturbed nutrient absorption. Common findings in cases of intestinal disease are hypoalbuminaemia, panhypoproteinaemia, hypomagnesaemia, low serum cobalamin, zinc deficiency and vitamin and trace element deficiencies.
The optimal nutritional approach for dogs and cats with IBD remains to be determined and probably varies from animal to animal, he said. However, implementation of sound nutritional practice could result in decreased utilisation or dosage of pharmacological therapy.
Culture-independent techniques
Prof. Simpson, who has a keen interest in IBD and especially the interplay between enteric bacteria and the host which leads to IBD, said that IBD was the term applied to a group of poorly understood enteropathies that commonly affected both animals and people.
But, he added, it is increasingly considered a consequence of uncontrolled intestinal inflammation in response to a combination of elusive environmental, enteric, luminal constituents (principally microbial and dietary) and immuno-regulatory factors in genetically susceptible animals.
Recent advances in molecular microbiology had enabled the analysis of complex bacterial communities without bacterial culture, he said.
Culture-independent analyses of bacterial 16S rDNA libraries in people revealed that only 30% of the faecal flora appeared cultivable, and there was significant variation in the flora in different gastrointestinal segments and luminal contents versus the mucosa of healthy individuals.
The application of these culture-independent techniques to people, dogs and cats with gastrointestinal disease has revealed that intestinal inflammation is typically associated with a floral shift from Gram-positive to Gram-negative bacteria, predominantly Enterobacteriaceae, he said.
Increased numbers of Enteobacteriaceae had been found to correlate with mucosal inflammation and clinical signs in cats with signs of gastrointestinal disease, and a novel group of adherent and invasive E. coli (AIEC) had been associated with intestinal inflammation in people and Boxer dogs with granulomatous colitis.
In many patients it remained to be determined if floral alterations were a cause or a consequence of the inflammation, but their discovery had provided new opportunities for therapeutic intervention, exemplified by intramucosal E. coli in Boxer dogs with GC, where eradication of invasive E. coli correlated with long-term clinical and histological remission, Prof. Simpson said.
Health benefits
Dr Benyacoub said that among the nutritional approaches to promote gastrointestinal tract physiology and health conditions, probiotics had gained considerable interest in the last two decades. They were commonly defined as live microorganisms that conferred health benefits to the host.
He pointed out that selected strains of probiotics had been used successfully to modulate the microbiota composition and favour a healthy pattern by promoting beneficial bacteria such as bifidobacteria and antagonising pathogens and stimulating immune defensive mechanisms, thus improving disease outcomes, including diarrhoea and immune-related disorders in different age populations. The most often-used probiotic genera in humans, farm animals and more recently in companion animals, were enterococci, lactobacilli and bifidobacteria, all normal inhabitants of their intestinal microbiota.
The mechanisms underlying the effects of probiotics, in particular against enteropathogenic infections, were not fully elucidated, he said. Among the different mechanisms postulated to play a role, the capacity of probiotic strains to modulate both innate and acquired immune defence mechanisms at the local and systemic level was particularly important to sustain protection.
The ability of probiotic bacteria to modulate the constituents of the intestinal microbiota and/or their metabolic activity is one mechanism by which they affect the immune system. However, a direct interaction of probiotics with the immune system underneath the gut mucosa was also likely, he said.
He believed that, as in humans, weaning, stress, dietary changes, use of antibiotics and intestinal infections were all conditions that affected the natural balance of the intestinal micobiota of pets and for which the application of probiotics might be beneficial.
“There is increasing evidence that specific strains of known probiotics can survive transit through the canine and feline GI tract, modify the microbiota composition and exert beneficial immune effects, including improvement of GI conditions such as diarrhoea, and modulate immune functions,” he said.
