Eleni Apostolatos, ’18, THURJ Writer

The old saying that we are what we eat rings true in nutritional genomics, a fairly new branch of science that studies the relationship between nutrition and genetics. The basis of nutritional genomics is the interaction between genes and nutrients: genes can affect how the body processes nutrients, and what we consume can impact the expression of genes. This understanding leads to the revelation that nutrition can in fact influence the expression of our genetic makeup and its manifestations—that is, us.

The personalized approach of Nutritional Genomics

Nutritional genomics is part of a larger movement that has been garnering popularity in recent years; personalized medicine, a novel perspective on medicine and health that focuses on patients’ intrinsic differences, tailors treatments to meet individual needs. Personalized medicine has already obtained considerable success in several areas of medicine, more recently including cancer genomics. The idea behind nutritional genomics is similar: a diet is personalized for individual patients to produce the greatest benefit for their wellbeing.

Jose M. Ordovas, Director of the Nutrition and Genomics Laboratory at Tufts University, wrote in his review of this novel branch of medicine that the field includes “nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome, and nutrigenetics, the major goal of which is to elucidate the effect of genetic variation on the interaction between diet and disease” (1). Nutritional genomics could thus yield important insights into how nutrition impacts DNA, proteins, and metabolites as well as how these modifications can be applied to avoid or delay the onset of disease.

 Epigenetic modifications: studies conducted in C. elegans

The belief that diet impacts health has been around since the early days of medicine; in 400 B.C., Hippocrates’ earnest advice to physicians was, “Leave your drugs in the chemist’s pot if you can heal your patient with food” (2). Food can’t directly modify gene sequences or DNA; gene expression, however, can be affected by nutrition. Various nutrients can activate or inhibit gene expression through epigenetic changes that modify the structure of chromatin, the material that makes up chromosomes.  These modifications either facilitate or limit necessary transcription machinery access to DNA, causing varying expression levels of certain regions of DNA. Epigenetic mechanisms include histone acetylation, which increases DNA expression, and DNA methylation, which represses DNA expression.  Some foods contain proteins such as histone acetylases and DNA methylases, which introduce such epigenetic modifications. Examples of nutrients that enact these changes include folate, vitamin B-12, and methionine, which impact DNA methylation by altering 1-carbon metabolism. Others, such as the water-soluble B vitamins biotin, niacin, and patothenic acid, impart histone alterations by adding or removing acetyl groups (3). Genetic variants generate different activity levels in biological pathways, which in turn result in varying expression levels  and phenotypic manifestations as a result of nutrient interactions. (4).

“It’s very hard to answer questions about the complex interaction between diet, gene expression and physiology in humans,” said A.J. Marian Walhout, PhD, the co-director of the Program in Systems Biology at the University of Massachusetts Medical School in a past published by the university, as studies have aimed to gain a more complete understanding of such processes. The Walhout Lab studied this complex interaction by using “a very tractable system—namely C. elegans—to ask precise questions about which components in diet can affect gene expression and physiological traits and ultimately disease, in humans” (5). The Walhout group observed that when the transparent roundworms are fed diets composed of different types of bacteria, their gene expression is significantly altered. Remarkably, 87 changes in gene expression were observed in C. elegans fed two diets. Worms that were fed Comamonas bacteria consistently developed faster, lived shorter lives and had fewer offspring than worms that were fed E. coli bacteria, a standard laboratory diet. The stark phenotypic differences between the two groups of worms demonstrate a  connection between diet, gene expression, and physiology that is still not fully understood.

Walhout’s study and others like it are relevant to humans because many organisms share common biological processes. In this case, the “same regulators that are influenced by diet in the worms control circadian rhythm in humans,” the internal body clock that regulates bodilyprocesses—and it is therefore now “know[n] that circadian rhythms are affected by diet,” according to Lesley MacNeil, PhD, a postdoctoral researcher in the Walhout Lab and one of the authors of the paper (5). The extent to which diet can affect circadian rhythms is currently being explored in other labs in an attempt to further elucidate the interaction between food and physiology. The results of the Walhout Lab’s study indicate that C. elegans and potentially other organisms can be used to develop a better understanding of the complex relationship between diet, gene expression, and physiology, particularly when it comes to human health.

 Applications of Nutritional Genomics

Nutritional genomics can extend beyond a personalized approach to nutrition; it may also fuel the growing field of genetically modified organisms (GMOs). In fact, nutritional genomics has the potential to help stem global hunger. David Bergvinson, the Director General of the International Crops Research for the Semi-Arid Tropics (ICRISAT), related in an interview that, “[t] he challenge of producing more nutritious food to feed 9 billion people in 2050 amid the threat of climate change is enormous. Next-generation genomics is one of the ‘best bets’ for sustainably eradicating hunger, malnutrition and poverty. This powerful tool can dramatically increase our capacity to utilize genetic diversity and develop highly nutritious, stress tolerant crop varieties faster and cheaper than conventional crop improvement practices” (4). Through continued study of the human genome and its response to nutrients, researchers may be able to provide guidance on how to best meet the requirements for good health.  In other words, the opposite of personalized medicine can also be true: an appropriate diet can be designed with food that meets nutritional requirements for the majority of genotypes.

While the field is still growing, and nutritional genomics has the potential to create preventative measures against disease, current knowledge is still limited and cannot guarantee significant benefits. It is important to note that lifestyle changes and nutrition are only a part of the equation. DNA is the blueprint that determines growth and development, but what we eat will not necessarily modify our code. External factors, like diet, can only improve or diminish health, but do not, as far as we know, offer a cure-all.  Consequently, the question of magnitude remains: how much of a role does food play in health? Over the next few years, further research on the role of nutrients in epigenetic mechanisms may provide a definite answer.

 

Bibliography

(1)Ordovas, J., & Mooser, V. (2004). Nutrigenomics and nutrigenetics. Current Opinion in Lipidology, 15(2), 101-8.

(2) Pray, Leslie. “Dieting for the Genome Generation.” The Scientist Magazine. LabX Media Group, 17 Jan. 2017. Web.

(3) Choi, Sang-Woon, and Simonetta Friso. “Epigenetics: A New Bridge between Nutrition and Health.” Advances in Nutrition: An International Review Journal. N.p., n.d. Web. 13 Apr. 2015.(2) Udani, Jay, Dr. “Nutrigenomics Can Make ‘Healthspans’ Longer.” Nutural Products Insider. Informa Exhibitions LLC, 3 Oct. 2014. Web. 13 Apr. 2015.

(4) Fenech, El-Sohemy, Cahill, Ferguson, French, Tai, . . . Head. (2011). Nutrigenetics and Nutrigenomics: Viewpoints on the Current Status and Applications in Nutrition Research and Practice. Journal of Nutrigenetics and Nutrigenomics, 4(2), 69-89.(5) “Next-generation Genomics Key to Global Food Security.” The Hindu. The Hindu, 21 Feb. 2015. Web.

(5) University of Massachusetts Medical School. “You are what you eat — even the littlest bites: Dietary influences tied to changes in gene expression.” ScienceDaily. ScienceDaily, 28 March 2013. <www.sciencedaily.com/releases/2013/03/130328125102.htm>.

(6) Macneil, Watson, Arda, Zhu, & Walhout. (2013). Diet-Induced Developmental Acceleration Independent of TOR and Insulin in C. elegans. Cell, 153(1), 240-252.

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