10 Nutrigenomics Breakthroughs from ten years of research (2008-2018)
‘You are what you eat’ is a phrase that might strike fear into your heart depending on what is in your mouth at the time! While the origins of this phrase are probably as old as mankind fundamental research now supports the importance of eating the right things, at the right time, both in humans and animals.
If our genes are the blueprint that defines who we are, it is how they express themselves in the presence of nutrition, to produce proteins. ‘Gene expression’ patterns caused by food, also called nutrigenomics, tell us if we are sick, how we will react if we get sick, and if what we are eating or doing can make us better.
A small chip (right), representing all the genes in the tissue of the individual being examined, allows scientists to predict precisely what effects to expect from dietary changes, showing which genes are activated and deactivated (in other words, turned “on” or “off”).
In the first of its kind, Alltech’s facility opened 10 years ago and was dedicated to the study animal nutrition’s impact on gene expression. This allowed scientists to determine in hours what outcomes to expect from feeding specific foods, feeds and dietary supplements to animals without waiting months or even years for results typical in farm trials.
Over those ten years nutrigenomics has now been used to
a) Understand how specific foods change gene expression
b) Quickly screening for new nutrients with similar benefits
c) Predict responses to novel nutrients or foods.
1. Truly AMAIZE-ing
Although considered ‘amazing’ by some farmers who used it Amaize was a product with an elusive mode of action. Cattle and other ‘ruminants’ rely upon their first stomach (the rumen) to breakdown fiber. Enzymes such as Amaize should help with this digestion process, and indeed using traditional techniques researchers had demonstrated that adding Amaize had demonstrated extremely significant results in terms of carcass weight gain for beef (average +10 kg) and milk production in dairy (1.5- 2 kg per day).
Examining tissue samples using gene expression told a different story; the enzyme's impact on the animal’s metabolic system showed that in fact the effects of Amaize are also anabolic, that is, they help the animal grow.
Several key changes were noted. Genes relating to the expression of insulin-like growth factor (IGF-1), insulin receptors and the growth hormone genes were affected positively. These genes all have a direct correlation in increasing metabolic activity and therefore body growth. Typically, when insulin goes up, insulin receptors levels decrease. Another example is how people have trouble regulating their blood sugar when they have diabetes. In the case of Amaize, both insulin and its receptors were increased so scientists set about discovering the “sweet spot”, i.e. right amount of Amaize to include. Too little or even too much adversely affected the ruminant and decreased the positive benefits of the enzyme.
Nutrigenomics allowed scientists to precisely understand the true function of Amaize, making it possible to issue specific recommendations to farmers of how and how much to incorporate into their cattle’s diets to maximize increase production and profitability. Primary Scientist: Dr. Karl Dawson
2. EconomasE: An Economical alternative to Vitamin E
Many consider EconomasE the first fundamental nutrigenomics innovation. In essence it is an algae-based antioxidant supplement, demonstrating similar biological functions as vitamin E, more economically.
Vitamin E is known throughout the world for its powerful antioxidant properties. Antioxidants inhibit the oxidation of other molecules, which can produce free radicals. Free radicals, unpaired loose electrons, cause damage to cells in the body and is why doctors tell you to eat certain berries, leafy greens and nuts; to protect and make you (your cells) healthier! A person who consumes antioxidants will be healthier in general and in better shape to fight off illness.
Humans aren’t the only ones to benefit from antioxidants; all animals do and for this reason Vitamin E is routinely included in the diets of all production animals. Vitamin E, however, is very expensive and producers often find ways to minimize its inclusion in their feed. Once consequence of this can be increased requirement for antibiotics. The history of antibiotics in feed is reviewed in this article.
Researchers were able to use nutrigenomics to identify Vitamin E mode of action, and then set about identifying other compounds or combinations with similar effects. An algae-based antioxidant proved capable of replicating the gene expression changes seen with vitamin and this was confirmed with 46 subsequent trials with poultry, swine and cattle. EconomasE maintained meat quality and the beneficial, protective antioxidative effects of vitamin E without the high price tag. Primary Scientist: Dr. Ronan Power, check out his research here!
3. Using Zn to address NE
Zn (the symbol for Zinc for those that slept through chemistry) is a trace mineral required by all animals to grow and develop properly. It aids the body’s ability to combat colds and infection. In animals it helps with a severe intestinal infection known as necrotic enteritis (NE) which costs the poultry industry alone an estimated $5 to $6 billion globally, and mortality rates of up to 1% per day.
Necrotic enteritis is caused by the pathogenic bacteria family of Clostridium perfringens resulting in lesions of the intestine that inhibit the absorption of nutrients, further weakening the sick animal and possible death. In the last few years, scientists have been searching ways to reduce the effects of necrotic enteritis in production animals such as poultry, pigs and cattle. Nutrigenomics research demonstrated that gene changes caused by the addition of bioplexed Zinc in the diets of these animals were favourable, especially when the animals immune systems were challenged by stress or even disease. Bioplex Zinc also greatly increases intestinal permeability, meaning animals are better able to absorb nutrients, are stronger, healthier and more suited to defend themselves against challenges.
Nutrigenomics confirmed that the form of zinc used is important. Forms such as Zinc Oxide and Zinc Sulphate for example, typically used in animal diets, and in human supplements, are less effective than those connected to mixed peptides, impacting how the Zinc is absorbed. Treating the animal in a holistic manner, supplying it with nutrients in the optimal form, the animal is far better prepared to fight off disease and infection, resulting in less antibiotic use and better efficiencies of food digestion, both of which will save the industry billions of dollars annually. Primary Scientist: Dr. Daniel Graugnard
4. Mitigating Myopathies in Meat
As recently as five years ago a condition known as “woody breast wasn’t even on the menu of concerns for chicken producers. Now, it is credited with losses conservatively estimated at $200 million dollars in the US and affects chicken producers in Brazil, Spain, and Italy amongst others. An affliction of the chicken breast it results in tough, chewy and otherwise inedible meat. The USDA’s Food Safety and Inspection Service (FSIS) has decreed that chicken meat must be inspected by hand to prevent adulterated meat from entering the market.
While genetics certainly play a factor, woody breast is generally considered to be directly correlated to how fast producers grow their chickens. Consider that in 1930, the average chicken was slaughtered at 2.5 pounds (1.1 Kg) and took 50 days to gain each pound of weight, and less than 100 years later, we grow chicken today to 6 to 8 pounds live weight, and they can put on a pound every 8 days!
At a scientific level fast growing chickens are being affected by hypoxia (low blood), increased oxidative stress, inflammation and an increase in fibrofatty tissue. From a consumer perspective this results in the chewy, though not toxic, chicken with unpleasant eating experience. Gene expression changes have allowed the development of a feed program which decreases the oxidative effects within the bird and an increase in normal tasting breast fillets. Primary Scientist: Dr. Rebecca Delles who suggests reading this article for further scientific reading on meat myopathies!
5. Actigen: A Force to be Reckoned With
If it sounds a bit more like a super hero than a nutritional supplement for animals perhaps there is a reason for that. For many years Bio-Mos, a mannan oligosaccharide, has been a star ingredient in animal feed, both in terms of improving performance naturally and in helping farmers replace antibiotics with a natural alternative. Bio-Mos achieved this by agglutinating damaging intestinal pathogens, improving intestinal health and nutrient absorption.
The challenge was that the nature of natural is variation: color, odor and particle size relating to the natural process of production. The challenge became, make it more concentrated, make it more economical and make it traceable. After four years the result was the product Actigen; but could scientists prove it was effective in animals? Enter Nutrigenomics.
Actigen is a mannose rich fraction (MRF) of Bio-Mos. Nutrigenomic research quickly confirmed its similarities to Bio-Mos, but also showing it to be 2.5 to 5 times more powerful, and a potent anti-inflammatory. The image to the left is a sample of hierarchical clustering and indicates how MRF affects gene expression and turns “on” the appropriate genes for improved animal performance.
Subsequent animal feeding trials proved Actigen’s ability to help animals to achieve their genetic potential, but without Nutrigenomics confirming its biological value would have taken months or years. Instead it was accomplished in weeks. Primary Scientist: Dr. Colm Moran who assisted in publishing this article demonstrating the research.
6. You are what your mother ate – The science of Epigenetics
Epigenetics, or how an environment impacts the expression of inherited genes, is the next science to promise to revolutionize the way we think of nutrition. In this case what the parents eat and the parents of their parents ate affects gene expression. And it’s not just nutrition. Studies have shown that overeating, undereating, exercise and smoking all have potential benefits or deleterious effects on the next or further generations.
Pregnant sows at the world’s largest pig farm were fed Actigen during the last trimester and demonstrated epigenetic benefits. Tissue samples from their off-spring demonstrated gene expression changes suggesting stronger immune systems and enhanced nutrient uptake. So as epigenetics suggests just by feeding the mothers Actigen, their pigs were much better off than those whose mothers did not receive it.
Healthier piglets will grow better, be more efficient, have stronger immune systems and less likelihood of disease infections. Better for the pigs, better for the farmers. Primary Scientist: Dr. Kristen Brennan published a research article showing the positive effects on piglets.
7. Programmed Nutrition: conditioning gene expression
Within the lifetime of the person or animal genes can be conditioned; that is constructing specific feeding regimes that prepare the genes with a specific diet, so that when the second diet is fed those genes express in ways that are beneficial for the animal. This can be especially of benefit in the cattle industry, where cattle are bred and born in one location and often exchange hands three or four times. This doesn’t encourage many farmers to feed their cattle for the long run. Programmed nutrition shows that feeding new-born animal supplements at specific levels and specific times their bodies can better learn to utilize and retain these nutrients. As the animal grows they become more efficient and require less nutrients than animals receiving excess supplements.
One example is Epnix. As part of a feeding program to create genetic conditioning, the timing of feeding Epnix to cattle is critical. It is a two-part process: the first part conditions the animal’s body to utilize nutrients better and the second part is actually feeding it those optimal nutrients.
Epnix is a natural feed program can positively improve cattle performance, meat quality and even reduce the environmental impact of beef farming. Animals fed the right combination of organic trace minerals at the right time results in better meat quality and consistency as well as a longer shelf life. When you are sifting through steaks and tenderloins in the supermarket, consider how the meat looks; healthier animals result in redder, juicier meat. Primary Scientists: Dr. Vaughn Holder. Published research is available here, then check out this podcast in which Dr. Holder further describes the incredible benefits of Epnix.
8. In ovo Feeding – feed the egg before the chicken
Typically, from when an egg is laid to when it hatches takes 21 days, so almost the same as the time it takes the chicken to grow. So it’s not surprising that farmers are increasing wondering what a chick gets to eat when it is inside in the egg. Not just the white of the egg, but whatever bacteria and possible infections are all a concern, so while antibiotics and disinfectants were the norm now our interest is in nutrition, probiotics and prebiotics.
Using nutrigenomics scientists can look at what happens when different nutrients are introduced into the eggs what effects they have. When used correctly In ovo (Latin for ‘inside the egg’) feeding methods can be a powerful way to control and prevent disease as well as improve the development and health of the animal.
Careful injections into the unhatched eggs tiny doses of water-soluble sugar called MR8, from a probiotic yeast, results in baby chicks with stronger immune systems at birth and more efficient digestive systems. Not only that, but their hatchability increased with more chicks born and less died in the first week. Nutrigenomics showed a more developed chick’s digestive system physiologically and structurally, giving the bird a strong head start when compared to chicks that didn’t get sugar.
Implementing in-ovo feeding requires special machines for use in hatcheries incubating thousands of eggs but the technology is already arriving so the future for chicks is bright. Primary Scientist: Dr. Rijin Xiao who helped author this abstract explaining the beneficial effects of MOS on incubated eggs.
9. Serving Salmon Sans Sea Lice
Fish have never been more popular. As such fish farming or aquaculture has become very important, in fact more fish now come from farms then are caught in the sea. Aquaculture comes with challenges for farmers, managing diseases and parasites. Sea lice alone cost the aquaculture industry an estimated $1 billion dollars a year. The threat of sea lice to salmon is not new and salmon have developed their own protection by the secretion of a mucous layer encompassing its scales. This works, but when the sea lice is big enough they can harm the fish and sometimes even kill it.
Until now no annotated gene chip for salmon existed (the only fish species available was zebra fish, more likely to be found in your child’s aquarium!). This new Salmon gene chip allows researchers to test all kinds of nutritional changes from a nutrigenomic perspective and already evidence has been generated showing how to reduce the threat of sea lice to salmon.
Scientists have learned that how to harness the natural immune system of the fish. Dr. Keith Filer and research team discovered how to help fish produce more of the mucous-producing cells, making them slimier and harder for the sea lice to latch on to. For more on sea lice and the salmon industry, check out “For salmon’s sake: Seeking solutions to sea lice.” Primary Scientist: Dr. Keith Filer
10. Rebooting our approach to Alzheimers
From human-kinds perspective probably the most important work at Alltech’s Nutrigenomics Center is that with AT-001. Nutrigenomic studies had indicated specific selenium containing nutrients had the ability to change biochemical pathways associated with many serious diseases such as Alzheimer’s or other neuro-degenerative diseases.
In collaboration with the late Dr. William Markesbery, the director at the University of Kentucky’s Sanders-Brown Center on Aging, Alltech began testing one of those compounds, AT-001, and it was evaluated using a well-established mouse model of Alzheimer’s disease (AD) to evaluate its effects on neurodegeneration.
AT-001 reduced the incidence of clumps of misfolded proteins, known as amyloid plaques often associated with Alzheimer’s, by 45-50% plaque in the brains of these AD mice. Furthermore, the overall destruction caused by oxidative damage in the brain tissue of these same animals was reduced. For example, oxidative damage to both DNA and RNA was reduced by 35% and 60%, respectively.
Now tested in other animal species and other tissues, AT-001 has found to significantly increase mitochondrial activity. Mitochondria are the organelles responsible for producing energy in cells and are thus essential for life. It is well documented in the scientific literature that even small decreases in mitochondrial activity are linked to the occurrence of at least 50 different illnesses. Some are indicated in the figure below.
These initial results have opened an entirely new field of research, evaluating the physiological impact of all the over 100 individual sub-components of AT-001. Three small selenium compounds have displayed remarkable activity in cell culture and animal models with type 2 diabetes. In addition, the compound in AT-001 which is responsible for the reduction in amyloid plaques has been identified and characterized. As for AT-001 itself; it is currently in Phase II human clinical trials in a population of elderly subjects who are at risk of developing AD. Primary Scientist: Dr. ZJ Lan
The past ten years have seen incredible scientific and technological developments in our understanding of nutrigenomics, and these are only a few of the breakthroughs we can expect to see as technology and data analytics continue to advance. Good news for animals, the consumer and the environment.
This blog based on articles with Alexa Potocki.
