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Nutrition and Health: Translating the Science of

NutriGenomics into Practice

Okezie I Aruoma

Department of Chemistry and Biochemistry, California State

University Los Angeles, Los Angeles, CA 90032, USA

Report Submitted in Partial Fulfilment of the Requirement for

Completion of the Course “Nutritional Aspects of

Biochemistry” Spring Semester 2019

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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 genome-

wide 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

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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

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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

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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

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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

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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 at-

risk 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).

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Table 1: Selected Predictive Autoantibody Tests

Disease/Disorder Autoantibody Tests Positive Predictive

Value

Years Prior to Clinical

Diagnosis

Addison’s Disease *Adrenal cortex antibodies 70 10

Celiac Disease *Anti-tissue transglutaminase

*Anti-endomysial antibodies

*HLA-DQ2 or DQ8 antigens

50-60%

50-60%

100%

7

Hashimoto’s Thyroiditis *Anti-thyroid peroxidase

antibodies (postpartum)

92% 7-10

Primary Biliary Cirrhosis *Anti-mitochondrial

antibodies

95% 26

Rheumatoid Arthritis *Rheumatoid factor

*Anti-cyclic citrullinated

peptide

62-88%

97%

14

Scleroderma *Anti-centromere antibodies

*Anti-topoisomerase I

antibodies

100%

11

Sjogren’s Syndrome *Anti-Ro and La antibodies 73% 5

SLE *RNP, Sm, dsDNA, Ro, La,

and cardioliptin antibodies

94-100% 7-10

Type I Diabetes *Pancreatic islet cell *Insulin

*65 kD glutamic acid

decarboxylase

*Tyrosine phosphatase-like

protein

43%

55%

42%

29%

14

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.

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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.

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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