Nutrigenomics

Nutrigenomics

Senthil Natesan

What is nutrigenomics?

• Nutrigenomics attempts to study the genome-wide influences of nutrition and to understand the mechanisms that underlie these genetic predispositions

• Patterns of gene expression, protein expression and metabolite production in response to particular nutrients or nutritional regimes can be viewed as ‘dietary signatures

• Nutrigenomics seeks to examine these dietary signatures in specific cells, tissues and organisms, and to understand how nutrition influences homeostasis.

Muller and Kersten, 2003.Nutrigenomics: goals and strategies. Nature reviews Genetics 4 :315-322

Muller and Kersten, 2003.Nutrigenomics: goals and strategies. Nature reviews Genetics 4 :315-322

In future, nutrigenomics tools should allow the collection of ‘healthy’ diet-related expressionsignatures as appropriate baseline data (panel a). By comparing these signatures with ‘stress’signatures (panel b) that are derived from nutrigenomics experiments, we might be able toidentify early molecular biomarkers for individuals with sensitive genotypes under sustainedmetabolic and pro-inflammatory stress that could lead to serious conditions such as cirrhosis orinsulin resistance.With enough early warning, dietary intervention might reverse this process,regain homeostatic control and prevent these conditions in at-risk groups

Holistic approach

• Foods are digested, absorbed and distributed in the body. Food stuffs contain macronutrients (carbohydrates, lipids and proteins) and micronutrients (vitamins, minerals, trace elements). These nutrients induce changes at RNA, protein and metabolite level in the receiving cell or organism.

• The corresponding profiling technologies, namely transcriptomics (gene expression analysis), proteomics (protein expression analysis) and metabolomics (metabolite profiling) are applied to better understand and assess these effects in a holistic fashion.

Kussmann et al.2008 Profiling techniques in nutrition and health research .Current Opinion in Biotechnology 19:83–99

Mulche et al. 2005 Nutrigenomics and nutrigenetics: the emerging faces of nutrition The FASEB Journal 19 : 1602-1616

Insulin resistance and type 2 diabetes mellitus

• T2DM is a metabolic disorder, stemming from either an insufficient secretion or impaired action of insulin, characterized by hyperglycemia, dyslipidemia, and associated with impaired carbohydrate, protein and lipid metabolism diets high in fat and energy have been repeatedly shown to play a fundamental role in the onset of T2DM.

• However, evidence exists that both environmental and genetic factors are important in the etiology of T2DM.

• Recent mechanistic work using mouse models with various genetic modifications affecting lipid metabolism have conclusively demonstrated a relationship between lipids and disease stateMulche et al. 2005 Nutrigenomics and nutrigenetics: the emerging

faces of nutrition The FASEB Journal 19 : 1602-1616

Genotype and nutrition

• The field of Nutrigenetics is rapidly discovering in molecular (sequence) detail those genetic differences across the human population that are related to differences in needs for or responses to various nutritional variables

• Nonetheless, as the genes responsible for human diversity are recognized, the capabilities of genotyping to provide individuals with actionable knowledge about their unique predispositions for diet, drugs, and lifestyle will invariably increase as both a scientific and commercial reality.Fay and Gernman 2008.Personalizing foods: is genotype necessary?

Current Opinion in Biotechnology 19:121–128

Environment x genotype = imprinting

Lifestage• The nutritional requirements of humans vary according tomany features

of an individual’s stage in life.Environment• The environment in which an individual lives is taken in this review to

include all aspects of exogenous inputs to their phenotypes, including acute and chronic, random and volitional, and chemical and behavioral.

Environment x genotype = imprinting• Environment at one stage of an individual’s life can exert persistent

effects on the nutritional phenotype later in life (imprinting, programming, memorization, or colonization). The explicit covalent modifications of DNA that persists through cell divisions are now recognized and are increasingly well described in the field of epigenetics

Fay and Gernman 2008.Personalizing foods: is genotype necessary? Current Opinion in Biotechnology 19:121–128

olfactory preference and nutrition

• The remarkable property of olfactory preference is the process by which positive and negative preferences for particular flavors are acquired in an individual as a series of complex, contextual memories early in life .

• This system of acquired flavor preferences underlies much of the cultural variation in foods and cuisines around the world.

• This also means that flavor preferences for foods with poor nutrient quality, if acquired by an individual early in life, will guide a life long habit of poor food choice

Fay and Gernman 2008.Personalizing foods: is genotype necessary? Current Opinion in Biotechnology 19:121–128

Nutrition and food science go genomic

• Diet and food components are prime environmental factors that affect the genome, transcriptome, proteome and metabolome, and this life-long interaction defines the health or disease state of an individual.

• Profiling technologies are used in basic-science applications for identifying the mode of action of foods or particular ingredients, and are similarly taken into the science-driven development of foods with a defined biofunctionality.

• Biomarker profiles and patterns derived from genomics applications in humans should guide nutrition and food science in developing evidence-based dietary recommendations and health-promoting foods.

Rist et al. 2006. Nutrition and food science go genomic TRENDS in Biotechnology 24(4): 172-178

Where do we stand, and where do we go from here?

• Genome–food interactions are the paradigm for the interplay between the human genome and its environment.

• Nutrition and food science are stepping into the genomics era, and it is becoming evident that nutrients and other food components are key factors in altering gene transcription, protein levels and functions, and the metabolome, which eventually translates into a health or disease state on the basis of a given genome

• Knowledge regarding the response of mammalian organisms to changes in diet or in response to individual nutrients and non-nutrient components of foods can be gathered by expression arrays, proteome analysis and metabolite profiling technologies

• All of these techniques should enable the determination of metabolic markers that can guide the assessment of the health status of humans and provide measures for food-derived effects on human metabolism.

Rist et al. 2006. Nutrition and food science go genomic TRENDS in Biotechnology 24(4): 172-178

Products Fabricatedfor Personalized Nutrition

The nutritional genomics approach has created hopes that gene-based nutrition planning can one day play a significant role in preventing chronic disease, and industry has an interest in using this knowledge for commercial purposes.Some relevant questions in this respect include

(a) whether the scientific evidence base is sufficiently strong to justify creating a special nutritional product;

(b) how personalized-nutrition products can reach the correct target group;(c) whether the advent of personalized-nutrition products will encourage

people to believe that only some individuals need to adopt a healthy diet or will create unwarranted or exaggerated hopes and expectations; and

(d ) how such a development can be counteracted.

Biobanks in Nutrigenomics

• A biobank is a repository of collected bodily substances or DNA often linkable to data on health or lifestyle of the donor.

• Related terms include gene bank, genetic biobank, DNA bank, or genetic database .

• Large population-based gene banks such as DeCode (from Iceland), the BioBank UK, the Estonian Genome Project, or the Genome Database of the Latvian Population

• Other types of biobanks include smaller collections of samples and data from single studies or derived within a clinical context that are stored in a systematic manner and may be linked to health relevant data