This week we will look at Gluten. Gluten-free foods are critical for the 1 in 100 people that have Celiac disease, but at this point, scientific evidence does not conclusively support the need for Gluten-free foods for the rest of people. It is possible that an additional small percentage of the population may benefit.
Welcome to the Food Genes and Me Blog! We are kicking off our FGM blog with a close look at a major interest of many people: Gluten. Interest in Gluten comes from the study of Celiac Disease, which results in inflammation, bloating, and diarrhea. The primary source of the symptoms comes from gluten ingestion. Gluten is a protein prevalent in wheat, rye, and barley products. When any protein is ingested, it is broken down to amino acids by enzymes released from the pancreas into the stomach. The resulting amino acid nutrients are absorbed as they pass through the small intestine. However, gluten protein is not completely broken down by the enzymes, and small peptides called Gliadins are released with the digested amino acids into the small intestine.
The Gliadins wreak havoc, one way by compromising protein complexes called tight junctions that seal cells to form a barrier that prevents intestinal contents such as bacteria from entering the blood. This is a severe disease and is only present in 1 in 100 to 1 in 170 people on average. The disease is most often caused by genetic mutations in the HLA-DQ2or HLA-DQ8 genes and has a high heritability of 75% . Thus, this is generally a genetic-based disorder.
HLA-DQ8 (blue) bound to gluten Gliadin peptide (red)
This week we are adding the HLA-DQ8 genetic variants that can cause Celiac disease to the Food Genes and Meanalysis program. If you have one of these mutations you should see a doctor and work with a dietician on a gluten free diet. This is the main reason why ~0.5-1% of people absolutely need a gluten free diet.However, if you enter any food market, you will see a rich supply of more expensive gluten free foods. Certainly they are not advertising to 1% of the population. The big question is does the average person need a gluten free diet? The answer is probably a few do, but possibly no. I reviewed the literature for Non-Celiac Gluten sensitivity (NCGS)looking for clinical trials that might support the recent marketing blitz for gluten. People with NCGS present with abdominal pain, diarrhea, nausea, bloating and flatulence. Some of these people who are self-reporting tend to have irritable bowel syndrome or Celiac Disease, but don’t know it. Those with irritable bowel syndrome respond to a different non-gluten component of wheat.The prevalence of NCGS is thought to be generally low, about 0.6-6%. And, the genetic component of NCGS determined by twin study heritability is nearlynon-existent with heritability estimates as low as 1%.
Given the low prevalence of NCGS, one must question the rigor of the clinical studies. Over the past decade,scientific studies with very large populations in the 10,000-100,000s are needed to reproduce clinical findings such as gluten sensitivity. The vast majority of published clinical trials testing gluten have less than a couple hundred people, thus sample size is a major concern for reproducibility and validity. In addition to population size, there are also confounding factors such as errors in self-reporting, not genotyping for Celiac Disease, dietary compliance during the study, and the gluten load ingested. Not surprisingly, a meta-analysis of 11 different gluten re-challenge studies of NCGS did not identify any significant differences . However, significant changes are observed in a meta-analysis of Irritable Bowel Syndrome and Celiac Disease for 36 combined studies with >15,000 participants.
Until such a time where a large meta-analysis of NCGS confirms a general role for gluten in the population, it seems like gluten-free products for the general population are just marketing hype, except for the small population that has Celiac Disease. However, NCGS is possible. It could represent a subclinical phenotype of Celiac Disease where polygenic sets of variants of small effect sizes contribute to presentation of milder Celiac Disease symptoms.
One possibility is that NCGS may be related to the microbiome as this seems to be having a larger and larger impact on our health. Certainly a Gliadin peptidefloating around the small intestine is great food for at least some of the 100s of species of bacteria that inhabit our intestines.Thus, the intestinal gut flora may significantly alter the load of Gliadin peptides. Likewise, ingestion load is likely to contribute to the level of Gliadins peptides that reach the small intestine. Eating a loaf of wheat bread could contribute to much higher levels of Gliadins peptideperhaps inducing symptoms in some people. More work will be needed to resolve the role of gluten in NCGS.
1 Elli L, Roncoroni L, Doneda L, Ciulla MM, Colombo R, Braidotti P, Bonura A &Bardella MT (2011) Imaging analysis of the gliadin direct effect on tight junctions in an in vitro three-dimensional Lovo cell line culture system. Toxicol In Vitro25, 45–50.
2 Khaleghi S, Ju JM, Lamba A & Murray JA (2016) The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate. Therap Adv Gastroenterol9, 37–49.
3 Fasano A &Catassi C (2012) Clinical practice. Celiac disease. N. Engl. J. Med.367, 2419–2426.
4 Kuja-Halkola R, Lebwohl B, Halfvarson J, Wijmenga C, Magnusson PKE &Ludvigsson JF (2016) Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins. Gut65, 1793–1798.
5 Czaja-Bulsa G (2015) Non coeliac gluten sensitivity - A new disease with gluten intolerance. Clin Nutr34, 189–194.
6 Lionetti E, Pulvirenti A, Vallorani M, Catassi G, Verma AK, Gatti S &Catassi C (2017) Re-challenge Studies in Non-celiac Gluten Sensitivity: A Systematic Review and Meta-Analysis. Front Physiol8, 621.
7 Irvine AJ, Chey WD & Ford AC (2017) Screening for Celiac Disease in Irritable Bowel Syndrome: An Updated Systematic Review and Meta-analysis. Am. J. Gastroenterol.112, 65–76.
Another open area for pursuing Gluten genotypes and gastro issues - a propensity for Irish heritage to be more susceptible.
Outstanding review - thank you!
Modern humans have existed for 6,000 generations, and we inherit traits, behaviors, and health vulnerabilities from our parents through DNA. Each person has 5-10 million variations in their DNA sequence. Yes, that is a lot of variation, but explains why you do not look like, act like, or have the same diet issues as your neighbors.
As we age, our bodies begin to fail in different ways, in part based on the DNA sequence variations we inherit, but also upon our exposure to environmental conditions, i.e. possibly the food we eat each day. Unfortunately, it is a very rare situation where there is certainty in what failure you will get. Again, this is partially because each person has a unique genetic makeup and a unique exposure to the environment.
To address this, scientists study large populations and determine what percentage of people has a specific condition. From these measurements, they can estimate the risk of seeing a particular condition, i.e. a genetic risk score. This is somewhat like your chances of rolling double sixes with a pair of dice – there are 36 possible combinations and double sixes is just one possible roll. Therefore, you have a 1 in 36 chance of rolling double sixes. Likewise, most human conditions have risks between 1 in 100 and 1 in 250,000. You may be thinking that 1 in 100 risk is a low risk, and “it’s not going to be me!” Well, but returning to dice as an example, let’s suppose you played some game and rolled the dice 108 times. Then on average, each set of 108 rolls would produce 3 rolls of double sixes! The same thing goes on with disease risk. Because there are so many different types of disease, each with their own risk, collectively you have a higher chance of contracting a disease. This is why the personalized dietary from advice is so powerful for living a healthy life.
Although we cannot be certain, one of the best predictors is your family history. This is the inherited risk. The other main risk for disease is environment, which includes your exposure to toxins, sunlight, radiation, chemicals, stress, physical injury, parasites, bacteria, viruses, and predators. Perhaps the most important environmental exposures that affect your risk is the type of food you eat every day.
Since most people eat frequently, it’s no surprise that the food you consume directly effects your health. But, you may not have known that interaction of your genes with your diet can radically change your risk for specific diseases and conditions. This field of research is known as nutrigenetics or nutrigenomics.
In your FGAM nutrigenetics report, we analyze your genetic file for several hundred DNA sequence variations. On average each person has a different set of 10-20 of the sequence variations from hundreds that are possible. Each of these variations are indicators of an increased risk for a condition and a food or supplement intervention that reduces the risk. FGAM was very careful to select only the DNA variants that have a strong basis based upon rigorous statistical tests in a scientific study. We next use this information to give you a list of five foods and portion that should be eaten daily and could reduce the inherited risk. Every time you come to the FGAM site, we may often provide you additional foods, so keep visiting your FGAM account.
To keep building our accuracy in genetic risk scoring, FGAM asks that you to donate your genetic information and complete a 5-10 min survey to advance FGAM research to discover new variants. You will benefit from your donation; by FGAM improving your personalized dietary advice. With your data we perform a genome wide association study (GWAS) for each survey question you answer. To perform these studies we do need 1,000s of participants and that is why we are asking you to be a team member. See our privacy agreement on how we take extra steps to secure your data and will only use it for FGAM research.
Submit candidate survey questions on FGAM’s contact us webpage as you would like, so we can further understand your interest, and together can investigate new DNA sequence variations of your interest.
In summary, FGAM is different from other genetics companies in several key areas:
1. FGAM focuses only on personalized foods and supplements based on your genetics.
2. FGAM only uses scientific studies with a strong scientific foundation and passes rigorous statistical tests.
3. FGAM is actively discovering new DNA sequences, and with your help will later not just be dependent on third-party published scientific studies.
4. FGAM believes it provides you the important information from genetic research because you eat every day; we do not provide information that has little impact on your life.
For more information or clarity of some of these descriptions, please also watch our YouTube videos: https://foodgenesandme.com/watch-videos.
The study of the interaction of dietary and genetic factors and its effect on metabolism, health status, and risk of disease. Nutrigenetics aims to identify how genetic variation affects response to nutrients. This knowledge can be applied to optimize health, and prevent or treat diseases. The ultimate aim of nutrigenetics is to offer people personalized nutrition based on their genetic makeup.
The genetic differences both within and among human populations. There may be multiple variants of any given gene in the human population.
Genetic risk refers your chance of inheriting a disorder, disease, or other trait. For human health, disorders, or other traits it would be great if we could definitively say yes or no, but this is not the case. Therefore, we assign a risk instead that is based on scientific studies. The risk is like rolling a dice. You have a 1 in 6 chance of rolling a 2. So, if 2 is some disease, on average 1 out of 6 people would get it.
Food Genes and Me™ is reporting personalized dietary advice, which is a report containing suggestions about foods, nutrients, and portion sizes that you should eat. This advice is based on your DNA sequence and solid scientific studies that link specific genetic variants with risks of disease or other outcomes.
FGAM diets are generated by scanning your uploaded genetic file for variants that affect a gene diet interaction outcome and meet rigorous statistical scientific metrics. Once a variant is identified we search a nutrient database to identify foods and portions that should be eaten daily to increase the risk of a favorable outcome.
Every day, your conscious choices in food selection will have been supported by studies that you’re your personal genes to food metabolism and other risks. No other genetic information affects people as directly as this, in their daily lives. Some of the information may be helpful in speaking with your healthcare provider, as well.
We expect that when your DNA sequence file is uploaded, it will take less than 24 hours to return your report to you, and usually within an hour.
Your information will only be used by Food Genes And Me for the discovery of new variants that can be used to improve you personalized dietary advice. We perform Genome Wide Association Studies to identify these variants.
Yes. Your survey information is not connected with a customer number, not your name, and once loaded it is removed from servers connected to the Internet. Likewise, once your genetic file is uploaded and processed, it is removed from servers connected to the Internet. The scientific research to discover variants is performed on computers not connected to the Internet.
Food Genes and Me will process a .vcf file and raw DNA files (note: NOT zip files) from the following:
After your login follow instructions here https://www.23andme.com/you/download
After your login follow instructions here https://dna-explained.com/2013/03/21/downloading-ancestrys-autosomal-dna-raw-data-file/
DNA Family Tree
After your login follow instructions here https://www.familytreedna.com/learn/user-guide/family-finder-myftdna/download-raw-data-page/
On the contact us page, please indicate your interest in an email or send us a letter.
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