Nutrigenomics for Companion Animals

Nutrigenomics is an emerging science that involves the study of molecular relationships between Nutrition and the response of Genes, in order to determine how even subtle genetic
changes can affect human health and animal health. Nutrigenomics
is linked to the concept that optimal nutrition can be designed based on an individual?s unique genetic makeup or genotype.

Nutrigenetics, a subcategory of nutrigenomics, is the retrospective analysis of genetic variations among individuals with regard to their clinical response
to specific nutrients.

Background

To address the increasing incidence (epidemiology) and recognition of diet-related
diseases in humans and animals, the role of diet and nutrition continues to be a major focus of study. Nutrition research is studying how dietary constituents
can optimize and maintain cellular, tissue, organ and whole body homeostasis, in order to prevent
disease. This necessitates an understanding of how nutrients act and interact at the molecular level [i.e. at the level of the gene, protein and metabolism].
Accordingly, nutrition research has shifted from epidemiology and physiology to molecular biology and genetics.

Nutrigenomics involves the characterization of gene products and the physiological function and interactions of these products. It also involves how nutrients
impact on the production and action of specific gene products and how these proteins in turn affect the response to nutrients.

The development of nutrigenomics has been aided by powerful advances in geneticresearch. Genetic variability,
the inter-individual differences in genetics, can affect metabolism as well as an individual?s phenotype. Genetic disorders of nutritional metabolism can cause pathophysiological effects that have been identified through examination of genetic polymorphisms. Simple examples
would be the genes associated with obesity or diabetes in various species, and vitamin B12 ?deficiency in Giant Schnauzers.

As there are thousands of potential gene polymorphisms which could cause only minor deviations in nutritional biochemistry, scientific efforts are fosused
on those changes of clinical significance. The tools to study the physiological impact of these deviations include those that measure the transcriptome,
such as DNA microarray, single nucleotide polymorphism arrays [SNPs] and genotyping. Tools that measure the proteome are less developed, and include gel electrophoresis, chromatography and mass spectrometry. Even less developed are methods for assessing the metabolome such as nuclear magnetic resonance imaging and mass spectrometry,
in combination with gas and liquid chromatography

Rationale and Aims

Nutrients relay signals that tell a specific cell in the body about the diet. A sensory system in the cell interprets information from nutrients
about the dietary environment. Once the nutrient interacts with this sensory system, it changes gene (genomics) and protein (proteomics) expression and metabolite production (metabolomics) accordingly.
Thus, different diets elicit different patterns of gene and protein expression and metabolite
production. Nutrigenomics describes the patterns of these effects, which are called molecular dietary signatures.

Part of the approach of nutrigenomics involves identifying markers of the early phase of diet -related
diseases, so that nutritional intervention can return the patient to a healthy state.
Another aim of nutrigenomics is being able to demonstrate the effect of biologically active food components on health, which should lead to the design of functional foods that will keep individuals
according to their own specific needs.

Applying Nutrigenomics to Companion Animals.

Recently, veterinary and nutrition scientists have begun applying animal genomics to the field of nutrition. Nutritional genomics and proteomics will play
a vital role in the future of pet foods. Functional genomics will emerge as important areas of study, now that genome maps for the dog and cat are
available.

Compared with the dog, where the genome is smaller in overall size than that of humans and is split into many more chromosomes (~ 2.7 vs 3.3 billion nucleotides,
and 39 vs 23 haploid chromosome number, respectively), the genome of the cat is more similar to that of humans (both have ~ 3.3 billion nucleotides,
and 19 vs 23 haploid chromosome number, respectively).

Studying and monitoring the health of dogs and cats parallels that of humans. Close to 500 canine and 300 feline genetic diseases have been described to
date. Molecular biological techniques have been used for several decades to identify the cause of single gene disorders in animals, which allows for
prevention and treatment strategies. Currently, at least 30 canine disease genes have been cloned and characterized. This has lead to development of
genetic mutation-based tests for diagnosis and carrier detection. Use of these tests permits elimination of carriers from the breeding population,
which ultimately decreases or eliminates the incidence of disease.

However, while determination of the DNA sequences of single gene mutations is feasible today, identifying the genetic loci responsible for complex genetic
diseases is a much more dificult task. Nevertheless, dogs and cats serve as excellent animal models for the nutritional diseases of other animal species
and humans. Although a genetic component exists for these conditions, nutrition plays a major role in the development and/or treatment of many of them.

Changing lifestyles in urban populations has lead to a significant increase in obesity and diabetes mellitus in humans and companion animals. The negative
health outcomes of obesity and diabetes observed in humans are also seen in dogs and cats. These are just two common examples of animal diseases having
both a nutritional causal and therapeutic component.

Use of canine and feline genetic maps will enhance understanding of nutrient metabolic pathways for optimizing the nutritional and health status of individual
animals. Certain dietary constituents such as vitamins A and D, zinc, and fatty acids can influence gene expression directly, whereas others such as
dietary fiber can have an indirect effect through changes in hormonal signaling, mechanical stimuli, or metabolites produced from gut microflora.

So-called “functional” food ingredients and herbal supplements are now being incorporated into animal as well as human foods. The effects of these nutrients
are being studied by gene expression profiling. Identifying and implementing genotype-nutrient interactions will require more complex adaptation and
nutrient design. The nature of these interactions will have to be determined and taken into account when formulating diets for an individual?s given
genotype.

Examples of nutrients currently added to pet foods include those intended to improve joint health such as glucosamine, chondroitin sulfate, and mussel);
protect the body from free radical damage such as vitamin E, ?-carotene, and selenium; improve skin such as omega-3 fatty acids; and gut health such
as oligosaccharides and probiotics.

Today, there are also pet foods designed for the animal?s life stages (e.g. puppy, adult and geriatric}, body type (e.g. toy, large and giant breeds),
and life style (e.g. active, growth and performance). But, the claimed benefits provided by these ?designer diets? may be well-suited for one dog and
not for another . As genetic polymorphisms are identified that affect nutritional status and disease in combination with the biomarkers used for their
detection, it should be possible to formulate diets not only for the prevention of structural abnormalities, but also for more complex diseases such
as diabetes, cancer, aging, behavioural changes, and heart disease.

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.


References:

  • Swanson et al. J. Nutr. 133:3033-3040, 2003
  • M?ller and Kersten. Nature Rev. Genetics, 4: 315 -322, 2003
  • Trayhurn Brit J Nutr. 89:1-2, 2003
  • Kaput et al. Pharmacogenomics. 8(4), 2007.

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