ABTRACT Adverse reactions to foods and adverse drug reactions are inherent in product defects, medication errors and differences in individual drug exposure. Pharmacogenetics is the study of genetic causes of individual variations in drug response and pharmacogenomics more broadly involves genomewide analysis of the genetic determinants of drug efficacy and toxicity. The similarity of nutritional genomics and pharmacogenomics stems from the innate goal to identify genetic variants associated with metabolism and disease. Thus, nutrigenomics can be thought of as encompassing gene-diet interactions involving diverse compounds that are present in even the simplest foods. The advances in the knowledge base of the complex interactions among genotype, diet, lifestyle, and environment is the cornerstone that continue to elicit changes in current medical practice to ultimately yield personalized nutrition recommendations and health and risk assessment. This information could be used to understand how foods and dietary supplements uniquely affect the health of individuals and, hence, wellness. The individual’s gut microbiota is not only paramount but pivotal in embracing the multiple-functional relationships with complex metabolic mechanisms involved in maintaining cellular homeostasis. The genetic revolution has ushered in an exciting era, one in which many new opportunities are expected for nutrition professionals with expertise in nutritional genomics. Key words: Personalized nutrition, nutritional genomics, pharmacogenomics, single nucleotide polymorphism; next generation sequencing; gene-diet Interactions; metabolic Diseases, wellness and genomics, Alzheimer’s disease and cognitive decline; autoimmune diseases; overt inflammation and chronic diseases, gut microbiome Introduction Nutritional Genomics is the study of the effects of foods and food constituents on gene expression. Nutritional Genomics aims to develop a rational means to optimize nutrition through the identification of the person's genotype and this defines the relationship between nutrients and human health. Individuals cannot change their genetics, but they can eat the right foods to support genetic predispositions, take the right supplements to support gene variations and promote normal cell function and structure. Indeed, poor diet can be a risk factor of disease. Given that dietary components can alter gene expression, the degree to which diet influences health and disease depends upon an individual’s genetic make-up, the use of pharmacogenomics technology should Page | 2 be well defined in order to fully embrace diagnostic, prognostic, predictive characteristic. There are many in-roads ahead in this realization. Figure 1. Personal genomics connect genotype to phenotype and provide insight into disease. Pharmacogenomics has helped understand some of the factors responsible for ADRs caused by high exposures and factors associated with the mechanism-of-action of the drug and examples continue to emerge where genetic markers identified patients at risk for serious, often life threatening ADRs before administration of drugs. (The reader is referred to Fernald et al (2011) and to the US FDA) website http://www.fda.gov/drugs/scienceresearch/researchareas/ pharmacogenetics. Single nucleotide polymorphisms are now recognized as the main cause of human genetic variability and are already a valuable resource for mapping complex genetic traits. The identification and validation of accurate biomarkers of individual responses to drug or biologic treatment remain prerequisite conditions ascribed to the development of PM and other evolving therapeutic strategies. The sequence variations in the genes for proteins involved in drug disposition can alter the pharmacokinetics of a drug, while sequence variations in drug target genes can change the pharmacodynamics of the drug (Figure 1). Understanding genomics The conference was prefaced with a session entitled NutriGenomics Primer: Foundational concepts for clinical practice, that emphasized the understanding genomics with a focus on Page | 3 nutrigenomics and clinical assessment and genomic validation (Figure 1). The molecular basis of disease provides the means for personalizing therapy with the expectation of increased therapeutic efficacy as the outcome. Because genetics is integrated into health care, medical, pharmacologic, and nutritional therapies will become more oriented toward the genotype of each person. Nutrition assessment and intervention will be the keys to preventing or mitigating the expression of diseases for which an individual is susceptible, essentially visualizing the potential interactions of the components of foods (Figure 2) can interact with the genetic material to produce biomolecules that work to maintain cellular homeostasis Figure 2. Nutrigenomics in the context anticipated role of dietary components: Nutritional genomics offers insight into ways to tailor the diets of individuals and populations. Personalized nutrition like its parallel in medicine presents a new way of dealing with individual nutritive health, using a “personalized” approached sustained by high through-put technologies including pharmacogenetics, pharmacogenomics and epigenetics interlinked with genomic medicine (Google slide from the presentation) Understanding the difference between genomics and genetics, how various SNPs (single nucleotide polymorphisms) work to convey risk or benefit to an individual not just alone but also in combination and how methylation and other factors contribute to the expression of DNA are imperative concepts for the practitioner wanting to use genomics as part of their arsenal of tools. Metabolic Adaptability of Genetic and Nutritional Responses Profiling of genetic nutritional responses can help in the determination of which specific foods that give the best biological response, based on an individual’s DNA. Interestingly, fatty acids in dietary triacylglycerols are transported from the intestines to the rest of the body by large Page | 4 lipoprotein particles called chylomicrons. Hormone signaling releases fatty acids from adipose tissue that bind to an abundant transport protein in serum called albumin. The fatty acids that are synthesized in the liver are carried through the body as triacylglycerols by very low-density lipoprotein particles. Fat is stored in fat cells (adipocytes). Obesity, especially childhood obesity, can be due to both, that is, more fat storage per cell, and to a larger number of adipocytes. In contrast, in normal healthy adults, the onset of old age and reduced metabolic rates leads to weight gain resulting primarily from storing more fat per cell (although adults can also add more fat cells if they become obese). The thematic review of Saini-Chohan et al., (2012) is worth perusing by the reader on fatty acid metabolism. The genomic disposition of the individual has a direct bearing in the control of metabolism which is nicely illustrated here. Translating the Science of Nutrigenomics into Practice A great deal has changed in the nutrigenetic testing environment since the first nutrigenetic tests appeared in the early 2000’s. The past two decades have seen an exponential growth in the number of genetic testing companies in the market place. Direct to consumer companies such as 23andMe, Ancestry.com and Helix personify how the consumer market has been captured with low cost tests and high technology, consumer friendly user interfaces. What is missing from this conversation is the use of practitioner-based nutrigenetic tests and the role of the health professional in their execution. Only a small percentage of genetic tests are being sold through health practitioners, yet countless publications have identified the health professional as key to the delivery and translation of nutrigenetic tests. There is need to understand the possible reasons why health professionals have not taken ownership of the growth, translation and utilisation of nutrigenetic tests. Neurocognition Personalized: Alzheimer’s and Neurocognition Genomics The limitations to care for clinicians that have access to their patients' genomes resides on the context that only a small percentage of the genome could be used because such data come from association studies, which tend to identify variants with small effect sizes and have limited applications for healthcare. Individuals have variations in the composition of their genetic characteristics (factored on strategies that embrace testing for candidate-genes and genome-wide association) that will affect the availability of functional proteins which ultimately impacts functional homeostasis and the outcome of drug therapy. The brain reflex-receptor mechanism in Page | 5 signaling for biomarkers and availability of enzymes for metabolism is of critical importance here. Biomarkers can be generically defined as unique characteristics that can be objectively measured as indicators of a biological or pathological process or pharmacological response to a therapeutic intervention, which then qualifies them to be potentially used across the whole translational medical research process. Biomarkers are therefore touted as the next frontier in the realm of modern medicine as they would represent the essentials in guiding treatment decisions that could enable complementary matching of specific drugs with individual patients, effective patient therapeutic dose and management of drug-related risks (Aruoma and Bahorun, 2010; Shah 200; Pacanowski and Zineh 2012). Neurocognition is great interest given the fundamental role that the brain reflex receptor mechanism plays in controlling dynamic equilibrium. Food, Mood and Metabolism The use of personalized nutrition to optimize diet for individuals based on genetic variation, environment and needs to incorporate the added value of personalization beyond standard ‘healthy’ advice that includes knowledge of differential responses to diet and variations metabolome associations across phenotypes. To take the context of the gut microbiome further, an interesting and unique view of the gut ecosystem is depicted in Figure 3 (Moya and Ferrer 2016). This presents a Multifunctional redundancy of intrinsic property of an environment that is subject to fluctuations. The authors argue that the gut microbiota stability may be affected within a temporal framework and in this context, bacteria turnover is a healthy feature expected in the gut. In order to ensure stability in the face of constant disturbance, microbiota species are continuously interchangeable by means of the metabolites produced by the action of gene products contained in the gut bacteria. Microbial genes and proteins and their metabolites in the gut grow from a simple structure in early life -usually dominated by bifidobacteria- to a complex structure in adults. Besides considering microbial composition and function, it is important to consider, over time, the contribution of resistance (no changes in microbiota composition after being subjected to disturbance), resilience (restoration of the initial composition after disturbance), and functional redundancy (recovering of the initial function despite compositional changes). These modifications are produced along a continuum and are shaped by age, geography, lifestyle-related Page | 6 factors, and medication. For instance, redundancy in the infant gut may be higher than that found in the adult gut. Figure 3. A network-biology approach depicting the gut microbiota is continuously changing in the gut environment. Envision health as a reflection of the diversity and composition of gut microbiota and its metabolic status (Adapted from Moya and Ferrer 2016). Applying Molecular DNA Technology in the Assessment of the GI Microbiota as Part of an Integrative Approach to Autoimmune Disease The hygiene hypothesis and changes in early environmental antigen exposure was postulated and briefly explored as a contributing factor in the emergence of the autoimmune epidemic in the Western industrialized societies (Weiss 2002). New opportunities for proactive screening for atrisk subjects for autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, diabetes, multiple sclerosis, lupus, and others using emerging predictive antibody testing was reviewed and discussed from the perspective of the clinical nutritionist and the nutritionally-minded physician. The various established predictive antibodies by disease, and their relative positive predictive value (PPV) are outlined in Table 1. The use of these testing methods is more of a predictive versus confirmatory fashion) (Leslie et al 2001; Vojdani 2008). Page | 7 Table 1: Selected Predictive Autoantibody Tests Disease/Disorder Autoantibody Tests Addison’s Disease Celiac Disease *Adrenal cortex antibodies *Anti-tissue transglutaminase *Anti-endomysial antibodies *HLA-DQ2 or DQ8 antigens Hashimoto’s Thyroiditis Primary Biliary Cirrhosis Rheumatoid Arthritis Scleroderma Sjogren’s Syndrome SLE Type I Diabetes *Anti-thyroid peroxidase antibodies (postpartum) *Anti-mitochondrial antibodies *Rheumatoid factor *Anti-cyclic citrullinated peptide *Anti-centromere antibodies *Anti-topoisomerase I antibodies *Anti-Ro and La antibodies *RNP, Sm, dsDNA, Ro, La, and cardioliptin antibodies *Pancreatic islet cell *Insulin *65 kD glutamic acid decarboxylase *Tyrosine phosphatase-like protein Positive Value 70 50-60% Predictive Years Prior to Clinical Diagnosis 10 7 50-60% 100% 92% 7-10 95% 26 62-88% 97% 14 100% 11 73% 94-100% 5 7-10 43% 55% 42% 14 29% CONCLUSION Genomics is a powerful tool that can help with the delivery of personalized medicine and personalized nutrition. Nutrigenetics/Nutrigenomics conceptualizes the research into the “relationship between genes and nutrients from basic biology to clinical practice.” By understanding how genes alter the body’s response to nutrition or how nutrition alters the body’s response to defective genes, scientists are unlocking the codes to health and longevity. The understanding of the gut microbial community (from composition to functional perspectives), needs to be interwoven with genomic cross-talk with active gene expression, protein synthesis, and metabolism. Given that dietary components can alter gene expression, practitioners need to now understand that the degree to which diet influences health and disease depends upon an individual’s genetic make-up. The use of pharmacogenomics technology must continue to be defined and embrace diagnostic, prognostic, predictive characteristic of diseases benchmarked on variabilities of respective biomarkers. Page | 8 REFERENCES Ames B. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res. 2000; 475: 7-20. Andersen SL, Sebastiani P, Dworkis DA, Feldman L, Perls TT. Health span approximates life span among many supercentenarians: Compression of morbidity at the approximate limit of life span. J Gerontol (Series A, Biol Sci Med Sci). 2012; 67: 395-405. Arkadianos I, Valdes AM, Marinos E, Florou A, Gill RD, Grimaldi KA. Improved weight management using genetic information to personalize a calorie- controlled diet. Nutr J. 2007; 6: 29. Aruoma OI, Bahorun,T. (2010): Special Issue on Pharmacogenomics and Pharmacogenetics: Future of Biomarkers in Personalized Medicine. Toxicology. 278: 161-248 TYPICAL EXAMPLE TO BE FOLLOWED Page | 9 
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