Food sensitivity has an immunological basis. Currently, it is not possible to distinguish a food which elicits an immunological response from the related intestinal disease or disorder that reflects the body’s reaction to the food ingredient or ingredients. The science of nutrigenomics seeks to provide a molecular understanding for how common dietary ingredients (i.e. nutrition) affect health by altering the expression and/or structure of an individual’s genetic makeup.
This is an emerging science that studies the molecular relationships between nutrition and the response of genes in promoting health . Different diets alter gene expression, and the production of proteins and metabolites. Specific nutrients affect body responses in a form defined as a “signature” an individual’s response = “molecular dietary signature”. The signature of a particular nutrient can vary between individuals according to their DNA.
Nutrigenomics identifies the food for an individual according to the molecular dietary signature of that individual. Individualized diets are proven in dogs for liver cleansing, arthritis, and obesity, but genetic differences lead to quantitative variations in dietary needs for energy and nutrients to maintain health. Certain diet-regulated genes play a role in the onset, incidence, progression, and/or severity of chronic diseases. Thus, dietary interventions based on animal’s nutritional requirement plus their genetic makeup (genotype) are used to prevent, mitigate or cure chronic disease.
Key Point = “Wholesome nutrition is the key to a healthy immune system and resistance to disease”.
FOOD SENSITIVITY & INTOLERANCE
Diet is a long recognized cause of hypersensitivity-like skin reactions in dogs, cats, & people. Type I hypersensitivity is well-documented, and Types III & IV hypersensitivity are suspected to occur. Immediate hypersensitivity occurs within minutes to hours; whereas delayed hypersensitivity occurs in hours to days. Delayed sensitivities occur 2-72 hours after eating; so it can be more difficult to connect symptoms with foods eaten. There is a high correlation of delayed sensitivity with the amount and frequency of food eaten.
A primary example of an immunologic food sensitivity or intolerance is sensitivity to wheat or other gluten foods, for example, barley, rice and oats. In the Irish Setter breed, wheat sensitive enteropathy is an heritable condition. Immunological reactions to gluten foods causes atrophy of the intestinal villi and inflammation of the small intestine, which, in turn, results in diarrhea and weight loss from malabsorption of fluid, electrolytes, and dietary nutrients. Even though chronic diarrhea is the most common symptom of this food sensitivity, there have been few studies of the prevalence of this condition in animals being presented to veterinarians with chronic diarrhea or other common gastrointestinal symptoms. Furthermore, there are no adequate methods in veterinary medicine to diagnose or noninvasively test for immunologic food sensitivities. This frequently results in either no diagnosis or the missed diagnosis of an immunologic food sensitivity or intolerance.
Despite this situation, many animals with gluten or other food sensitivity or intolerance do not have diarrhea or weight loss, but instead have other signs and symptoms such as vague abdominal pain, nausea, chronic fatigue, constipation, poor growth and maturity, iron deficiency anemia, osteoporosis, seizures or other neurologic disorders, or even just elevated serum liver enzyme levels. Some animals may be asymptomatic.
Furthermore, animals with gluten or other food sensitivity or intolerance may not have fully developed intestinal lesions. Therefore, the immunologic food sensitivity or intolerance of these animals may not be properly diagnosed using known testing methods, such as endoscopic intestinal biopsy and blood or serum testing. Additionally, these animals may present with other immunologic diseases such as the autoimmune diseases of skin, liver, joints, kidneys, pancreas, and thyroid gland, or microscopic colitis.
Delayed food-related sensitivities begin in the gastrointestinal (GI) tract when the intestinal lining becomes hyperpermeable. This problem is known as "leaky gut syndrome" or intestinal dysbiosis, and is defined as an increase in permeability of the intestinal mucosa to partially digested protein macromolecules, micromolecules, antigens and toxins. The immunological reaction to these proteins or other molecules in the liver initiates and perpetuates chronic food sensitivity or intolerance. When the gut is unhealthy, the rest of the body is unhealthy. The disease process that ensues is typically chronic or intermittent and often involves the gut and skin, as well as internal organs such as the liver. GI tract function is disrupted when the lining of the gut is inflamed or damaged. With a leaky gut, large food antigens can be absorbed into the body. The body's defense systems then attack this antigen or antigens and the result is the production of antibodies against what was once a harmless, innocuous food ingredient. These IgG antibodies and immune complexes are formed in the bloodstream and circulate throughout the body where they can damage other tissues along the way.
Immune complexes containing large food antigens enter the blood from the gastro-intestinal tract then travel through the liver where most immune complexes are removed. However, if circulating immune complexes pass the liver filtering system, they may cause injury to many body tissues. Malabsorption of food particles from the gastro-intestinal tract can also travel by lymphatic drainage to the body. The lymph channels in the gut wall converge at the thoracic duct which drains its contents into the large thoracic veins. This combination of antibody with complement in the blood stream becomes a circulating immune complex. Immune complexes subsequently attach to receptors on red and white blood cells and then these altered cells are cleared by the body’s liver or spleen (reticuloendothelial system).
Any circulating immune complexes that are not removed by the reticuloendothelian system of the liver (or spleen) can activate the complement cascade. Individuals with more immune complexes on their red blood cells are the ones that suffer from chronic food sensitivities or intolerances. Circulating immune complexes also can damage the integrity of blood vessel capillaries which in turn can trigger inflammatory events.
Delayed food sensitivities in people are extremely common and can be manifested by gastrointestinal, neurological, pulmonary, dermatologic, ear, nose and throat, musculoskeletal, genitourinary, cardiovascular and endocrine problems.
Primary food allergens are : corn, wheat, soy, beef, eggs, milk.
Secondary food allergens are: lamb, rabbit, venison, buffalo, chicken, turkey, barley, millet, oatmeal, salmon, white fish, rice, quinoa, potatoes.
Food intolerance is the third most common after flea bite sensitivity and atopy (inhalant allergy), and food intolerance makes up 1-10% of all allergic skin disease. It mimics other skin syndromes. Food intolerance has no age, breed, or sex predilection. Most affected animals have been eating the offending foods for more than 2 years. The major complaint is pruritis (itching), which is bilateral, and there is often inflammation of the external ear canals (otitis externa). Secondary skin disease such as seborrhea (both dry or oily) and pyoderma is common.
OPTIONS FOR MANAGEMENT & THERAPY
Create a healthy acid-base balance within tissues through optimal nutrition. Changing the proportions of macro-nutrients and micro-nutrients in different nutrient and food products is important in obtaining the right tissue balance. Use diet elimination trials, each for 3-6 weeks; but, appreciate that there is often poor compliance. Diet must be individualized, using nutrigenomic principles. Studies have indicated that specialized nutrient intake extends and improves life, delays onset and slows progression of disease, and enhances the quality of life of animals.
Avoid additives and supplements, and avoid switching often from diet to diet .1-15% of cases have concurrent GI tract issues, some cases have swollen lymph nodes, especially with cats. Affected pets have tension-fatigue, malaise, and dullness. Effects are non-seasonal and poorly responsive to steroids.
DIAGNOSTICS FOR FOOD SENSTIVITY /INTOLERANCE (DIETARY DIAGNOSTICS)
Food Sensitivity -- Previous Testing
Typically based on IgE, IgG and immune complexes with complement, these tests have high sensitivity but lower individual specificity. Measures only more immediate-type reactions.
The “gold standard” for food allergy testing in the dog has previously been the food elimination trial and allergen provocation. But, testing for this disorder uses expensive and unsightly skin patch testing or serum allergy screening that lack specificity.
However, there is poor correlation between serum IgE and IgG antibody testing and clinical experience in resolving disease in both humans and dogs. Dogs with atopic and GI tract disease have higher levels of serum IgE and IgG antibodies than normal dogs, and the antigen causing the reaction is contained in the diet.
Food Sensitivity -- Newer Testing
Newer tests can use serum, saliva or feces in a simple ELISA format or other immunoassay platforms. They identify IgG, IgA , or immune complexes to foods in serum, and IgA or IgM antibodies to foods in saliva. Antibodies to foods appear in saliva several months before the GI tract diagnosis of IBD (inflammatory bowel disease) or the “leaky gut syndrome” (intestinal dysbiosis). Saliva testing can thus reveal the latent or pre-clinical form of food sensitivity.
IgA, especially, but also IgM, are the important antibodies generated by immunological reactions and are expressed as secretory immunity in saliva, as well as other body fluids like tears and breast milk. IgE serology has been found to offer no advantage a diagnosis by dietary trial, because it had a seventh sensitivity of 14%, specificity of 87%, positive predictive value of 40% and negative predictive value of 61%. Thus, this form of serum food allergy testing is inadequate for clinical diagnostic purposes.
Only by looking at secretory immune responses to IgA and IgM in saliva (and serum) in people has a direct correlation between results and clinical allergic reactivity been described.
FOOD SENSITIVITY -- FUTURE TESTING AT THREE LEVELS
Saliva Screening Kit --- Point-of-Service (POS) owner/ vet clinic testing; Tests for salivary IgA and IgM reactants in healthy pets and those with known or suspected food intolerances.
Pet owner obtains test kit [from vet or pet supply store], follows directions, adds saliva, seals kit, sends to diagnostic laboratory. Check saliva several times a year .
Serum Screening Kit – further vet and laboratory serum testing.
For those dogs reacting to saliva test, client goes to veterinarian, blood drawn and serum sent to diagnostic laboratory.
DNA/RNA Microarray “Heat Map” -- vet and laboratory heat map genetic testing; (identifies pets needing individualized nutrigenomic foods).
SUMMARY: In summary, animal nutrition professionals need to be able to prescribe or recommend nutrients and diet formulations on the basis of more precise knowledge of how nutrients or food components interact at the level of the genome, where these constituents act by “up- or down-regulating” target genes. Diets for animals should be designed and tailored to the genome or genomic profile of individuals in order to optimize physiological homeostasis, disease prevention and treatment, and productive, athletic, obedience or reproductive performances.
The molecular dietary signature of an individual describes the pattern of the interaction between the nutritional environment and genome, also termed nutrigenomics. The basic concept is that chemical nutrients affect gene expressions in a specific mode by switching from health to a pathophysical condition or vice versa. The advancement of knowledge about human and animal genomes and the breadth of biotechnology offer the opportunity to individualize dietary intervention to prevent, mitigate or cure chronic diseases. The concept applies not only to companion animals and laboratory animals, but also to nutrient-genome interactions in farm animals.
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[Excerpted with permission from 2010 AHVMA Proceedings]
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