Veterinary nutrigenomics combines genetics and nutrition to develop optimal diets for companion animals, a field in which researchers and pet food manufacturers are investing significant amounts of time and money. At the University of Illinois, Kelly S. Swanson, Ph.D., and his team are using DNA-based sequencing techniques to characterize the canine and feline gastrointestinal tracts. They are looking at what happens in tissue when animals are fed one diet versus another. The results may lead to a better understanding of the microbial profile and metabolic pathways of animals with varying dietary regimens and at different stages of health and life. Many questions need to be answered before the ultimate goal can be achieved: creating individual diets that make optimal use of, and even manipulate, gene expression. “The dog and cat genome sequence data is being utilized in research, taking genomic biology to gain a better understanding of dog and cat physiology and how nutrition contributes to health and disease,” says Dr. Swanson, an assistant professor of animal and nutritional sciences in the , department of animal sciences. “Genomics in pets is being used to study microbial populations and gene expression changes in blood and various tissues. “Known genomic data is also being used to further understand nutrient-gene interactions within the dog and cat,” Swanson says. “Often the terms ‘nutrigenetics’ and ‘nutrigenomics’ are confused. Nutrigenetics is focused on identifying how genetic background affects the response to a nutrient or diet. In contrast, nutrigenomics is focused on measuring how a nutrient or diet affects gene expression.” Swanson says his goal of identifying why and how genes are expressed is an arduous process considering that most mammalian genomes contain 20,000 to 25,000 genes, which interact in complex ways. Identifying the genetic basis for disease is difficult. Even monogenic diseases are affected by a single spontaneous mutation. “We aren’t sure why some dogs as they age, for example, are more susceptible to disease,” Swanson says. “We’re looking at obesity and how spaying or neutering an animal affects them. Often, animals want to eat more after surgery. We want to know if giving them a certain diet would alter this behavior. We want to know how certain genes are being expressed in this scenario.” Swanson’s laboratory and others have identified molecular changes in adipose and skeletal muscle tissues during weight gain and loss after spay/neuter procedures in dogs (beagles) and cats (domestic shorthairs). “These studies have suggested the potential role of specific nutrients or phytochemicals, such as estrogenic-like compounds or green tea polyphenols, that may aid in healthy weight maintenance and deserve more attention in future research,” Swanson says. Swanson explains that many canine diseases, such as hip dysplasia, are affected by hundreds of genes and numerous environmental factors, including diet. The field of nutrigenomics is all about its potential, he says, adding that devising individualized dog or cat food based solely on a blood sample is years in the future. Swanson and Lawrence Schook, Ph.D., director of the Division of Biomedical Sciences at the University of Illinois, studied how diet affected the digestive tract of young and old dogs and whether identifiable gene expression changes were present. This was the first known research of its type and one day may lead to designing diets with respect to an animal’s breed or predisposition to diabetes or obesity. More Than a Test “We need to find answers to the gray areas,” Swanson says. “Veterinarians are treating animals for diseases and problems and are interested in genetic tests that determine if an animal has a certain condition. But we are looking at how genes are being expressed in animals with a disease as compared to others. We don’t just want a test; we want to know how to avoid or suspend disease through understanding the gene expression and diet.” Swanson stresses that nutrigenomic research isn’t looking into creating mutations in deoxyribonucleic acid (DNA); it’s looking at how to express a gene better. Nestlé Purina PetCare Co. of St. Louis has been studying molecular nutrition, which includes nutrigenomics, for years, says Rondo P. Middleton, Ph.D., a senior research scientist for the company. “Nutrigenomics and the biological processes that it encompasses have been around since the beginning of life,” Dr. Middleton says. “It is only recently that we have had the technology to study nutrition at this level and magnitude. Nutrigenomic-type studies have increased our appreciation for the role nutrition plays in the modulation of biological processes. So in this sense, it is vital to the pet that nutrition research is conducted at this level.” Specialized nutrition is in its infancy, he says, but he lists diabetes, obesity, osteoarthritis and brain function diets that the company produces as the results of nutrigenomic research. “Science has come so far, so fast, but it is only the beginning,” Middleton says. “We have made great strides in uncovering many of the processes that occur in a cell, tissue or animal in response to nutrients. At the same time, however, we are only now starting to sort this out and give it true biological meaning.” Middleton joined Nestlé Purina’s molecular nutrition group in 1998. The company prefers the term “molecular nutrition” to “nutrigenomics,” saying molecular nutrition includes nutrigenomics but utilizes other molecular tools and biological systems such as pure genetics (heritable traits), metabolomics (study of metabolites) and epigenetics. “We employ the use of multiple -omics platforms in our research,” Middleton says. “These platforms can measure tens or hundreds of thousands of measurements at a time. It allows the researcher to investigate what changes in biology are occurring by pushing the limits of detecting all within that system. An example is transcriptomics and microarrays. Microarrays have the ability to measure nearly all transcripts [mRNAs, copies of genes about to be translated into proteins] in a cell. This becomes very powerful to the researcher. “We can now let the cell tell us what is going on. We use this to not only characterize a physical state — growth, health, disease, etc. — but also as a means to study how nutrients have affected that issue in the cell. This is performed in a noninvasive way for the pets, utilizing in vitro techniques.” When Middleton Nestlé Purina, he and the group developed a canine microarray to investigate molecular changes associated with canine osteoarthritis. “We then used this and the knowledge we obtained about the disease, along with other technologies, to develop the Purina Veterinary Diet JM. JM was the first diet to use omega-3 fatty acids to help manage osteoarthritis in dogs,” Middleton says. “The JM diet utilizes the anti-inflammatory properties of omega-3 fatty acids to nutritionally address the inflammation associated with osteoarthritis. This includes the positive modulation of very specific molecular changes identified in our canine osteoarthritis research. This is just one example of many that we have performed or are currently in the process of researching.” Wayne Carter, DVM, Ph.D., Dipl. ACVIM, of Hill’s Pet Nutrition in Topeka, Kan., says the company has been using its research on nutrigenomics to design foods that line shelves today, including the Science Diet and Prescription Diet lines. The company also shares its findings. “We identified 3 million single nucleotide polymorphisms (SNPs) and donated the data along with $1 million to the Morris Animal Foundation to help identify genetic differences between cats in order to determine the association between a genetic problem and disease,” says Dr. Carter, Hill’s vice president of global research. Carter says Hill’s recently completed significant studies of gene expression in aging dogs and cats and wants to better understand how nutrigenomics can improve health from a disease perspective. “Canine and feline obesity is literally an epidemic which parallels that in humans,” Carter says. “Our R/D weight reduction diet was formulated to reduce weight in overweight dogs and cats. We are developing new nutrition concepts that can significantly change metabolism in cats. Not only does this keep weight in check, but it reduces the incidence of diabetes mellitus.” The 2010 American Animal Hospital Association’s Nutritional Assessment Guidelines, sponsored by Hill’s, recommend that a nutrition assessment be done during every veterinary exam, something Carter says raises awareness of the link between diet and health. What’s Next Joseph J. Wakshlag, DVM, Ph.D., Dipl. ACVN, describes nutrigenomics as the wave of the future in veterinary nutrition. “This research will be highly received by veterinary clients because nutrition is widely discussed and understood by owners,” says Dr. Wakshlag, an assistant professor of clinical nutrition at the Cornell University College of Veterinary Medicine. “I’m sure they’ll be interested in learning what diet can do and how it can affect an individual’s genetic profile.” Richard C. Hill, VetMB, Ph.D., MRCVS, expects research findings to as the puzzle pieces fit together to form a larger picture. “Much of the information released about nutrigenomics is speculative and forward thinking,” says Dr. Hill, the Waltham associate professor of small animal internal medicine and clinical nutrition sat the University of Florida College of Veterinary Medicine. “A lot of funding for the research is coming from pet food manufacturers, who hold onto their research findings long after they’re discovered. With this idea being so new, I’m interested in watching it develop and seeing the significant changes in nutrition as it relates to genetics.” Illinois’ Swanson says nutrigenomics continues to enhance the understanding of canine and feline metabolism and holds great potential for improving pet nutrition and health. “This field is in its infancy. Initial publications have shown great promise, highlighting dietary strategies for further testing or inclusion in pet foods,” Swanson says.
