SUMMARY: I am beyond excited to begin 2019 with the announcement of a groundbreaking microbiome study that I’ve been asked to help spread the word on! The study, called the MELODY trial, peels back the layers of microbiome influence further than any study I’ve seen to date because it moves the needle for microbiome manipulation PAST the immediate host to hopefully influence and alter the health of the newborn! HOW? The MELODY Trial will recruit childbearing aged women to investigate if changing thematernal diet can reduce transmission of disease to the newborn! The Melody Trial will focus on Inflammatory Bowel Disease (IBD) because children born to mothers with IBD have increased risk of IBD. Participant recruitment is targeted to begin mid-January, 2019. Its website is coming soon, and I’ll post that info ASAP! However, to start this discussion and catch all up to speed, this post explains another study called the MECONIUM Study (see the link here) and its EIGHT publications are below! MECONIUM stands for Exploring MEChanisms Of disease trasmission IUtero through the Microbiome.I’m starting here because the MELODY trial is based on the preliminary findings of the MECONIUM Study!The primary investigating lab for both studies is Peter Lab, Icahn School of Medicine at Mount Sinai. The MECONIUM Study was a prospective study that explored the role IBD plays in the composition of the maternal and infant microbiome. The MECONIUM Studyfound that the dysbiotic microbiome seen in infants born to mothers with IBD can be improved when ENVIRONMENTAL factors known to have a negative effect on the microbiome are ABSENT in early life. In particular, the sub-optimal microbiome of babies born to IBD mothers were MITIGATED in early life when the baby was born vaginally, was not exposed to antibiotics, and was exclusively or partially breastfed. Because of these findings, and since DIET is also considered an environmental factor that can change the gut microbiome, the MELODY Trial investigates if IBD mothers consuming the UMass IBD-AID diet (a diet shown to change the gut microbiome to anti-inflammatory, aid in repair of the gut, and help restore balance to the immune system to help induce remission for IBD), also alters the vaginal microbiome and reduces the risk of transmitting the dysbiotic disease-prone microbiome to the newborn. Guys, if the MELODY Trial works for IBD, will this strategy work for other diseases?!? Please, do your part and share this info with your friends, daughters, gynecologists, GI docs, doulas… Lets load this cohort quickly and move the needle to make the future better for our next generation! We’ve messed so many things up microbiome-wise, WE OWE OUR CHILDREN THIS!
SUMMARY: This post explains the disease epigenetics process because most think your genes are your destiny. That is actually not true. You are more than the genes you inherit from your parents! Genes predispose you to the disease (~66% of “you” is determined by your genetics), but the remaining 33% is influenced byepigenetic changes to the genes, and that is one mechanism through which disease is triggered, [Mellor, 2015 University of Oxford Podcasts].That is why they study DNA identical twins having discordance for the same disease — they find epigenetic differences [Insights from Identical Twins] [NovaScienceNow, Epigenetics] While it is often unknown if epigenetic differences are a cause or a consequence of disease, many studies are providing evidence suggesting a potential role for epigenetic alterations in the pathophysiology (e.g. Type 2 Diabetes, asthma, brain disorders and neurodegeneration, Alzheimer’s, autism, Lupus, Chronic Fatigue Syndrome, colon and other cancers, Parkinson’s, ALS…).The bottom line: Even though you might be “predisposed” to disease (e.g. you have a genetic pre-disposition tendency to Alzheimer’s, anxiety, arthritis, autoimmune disorders, cardiovascular disease, depression, diabetes, hypertension, metabolic syndrome, obesity, and cancer — any disease with epigenetic involvement which seems to be all of them) you can STOP and REVERSE the epigenetic changes that trigger disease by modifying factors that affect epigenetics such as nutrition, stress, toxicity, exercise and drugs.[Mellor, 2015 University of Oxford Podcasts] [NIH, NICHD] [Moosav et al 2016] [Szarc vel Szic et al 2015] [Wopereis et al 2014] [Hartzell et al 2012] [University of Utah, Nutrition & Epigenetics] One whopping impact of these factors is to pierce the disease epigenetic process by altering the microbiome. The microbiome is what makes identical twins, not identical! And it’s the microbiome consequent metabolites (which is where over 70% of our immunity resides) that can changeepigenetic mechanisms (like methylation and histone modification — NOTE: I won’t be “teaching” these mechanisms, I will however explain enough that you can EASILY understand the concept)which have onward effects including triggering or reversing disease in those predisposed. What this means is that you actually have a say in if you turn on or off genes with consequent trigger (or reversal) of disease.The recognition that environment, not genetics, is the primary driver of health and disease carries a strong message of personal empowerment and responsibility. Thus, included is a special section — EPIGENETIC EXPERT SUGGESTIONS FOR EATING FOR YOUR EPIGENOME!BAM — they sound a lot like those therapeutic diets I teach and blog about! Don’t be duped. A lot of disease is preventable — [WHO] says over 80% of all heart disease, stroke and type 2 diabetes AND over 40% of cancer! From the grim stats below, if you don’t already have disease you likely will and sooner than you expect! A balanced lifestyle that includes a healthy diet, exercise, & avoiding exposure to contaminants, may in the long run create a healthy epigenome. [TedED, What is Epgenetics? -Carlos Guerrero Bosagna.]Time to empower yourself to use epigenetics modifications to keep or move yourself off diseasespan!
♥ “Epigenetic modification of disease-related genes can contribute to diagnosis (biomarker) as well as disease prevention or progression.”
The Grim Disease Incidence Stats: If you don’t have chronic disease now, you likely will, & sooner than you may expect.
More than half the population has one chronic disease (it is autoimmune for 20% of those, mostly women) AND almost a third of the population has multiple chronic diseases.
67% of the working age 18 to 64 years have multiple chronic disease — 18% if aged 18 to 44 years, 49% if aged 45 to 64 years!
Even the young are not spared. 27% of 0 to 17 yr olds have one or more chronic disease!
The last slide shows what those diseases are by age!
AND IT IS ALL LARGELY PREVENTABLE!
WHO says,“The major causes of chronic diseases are known, and if these [known] risk factors were eliminated, at least 80% of all heart disease, stroke and type 2 diabetes AND over 40% of cancer would be prevented.
Learn the Disease Epigenetics Process the EASY way: Entertaining videos!
First, the difference between a genetic vs an epigenetic change is that the epigenetic change does NOT actuallychange the sequence:
Epigenetics and its Implications for Public Health, Genetic vs Epigenetic Change, http://www.oregon.gov/oha/PH/HEALTHYPEOPLEFAMILIES/DATAREPORTS/Documents/Epigenetics.pdf
TO BEST UNDERSTAND WHAT EPIGENETICS IS, LOOK OVER THOSE LAST TWO SLIDES BELOW FOR THE MOST BRILLIANT VISUAL DEMONSTRATION I’VE SEEN YET! NOTICE HOW THE PUNCTUATION VARIANCE DRAMATICALLY CHANGES UP THE DIALOGUE CONTEXT. SO TOO WITH EPIGENETICS. THOUGH EPIGENETICS DOES NOT “CHANGE UP” THE DNA, AN EPIGENETIC CHANGE READS THE INFORMATION DIFFERENTLY AND EXPRESSES GENES ACCORDINGLY. The epigenetic change makes genes unwind (aka turn on and be readable), or tighten up (aka turning them off and making them unreadable). THAT CAN BE BENEFICIAL OR DETRIMENTAL TO HEALTH AND DISEASE STATUS.
Note ⇒ Don’t get hung up on understanding the specific methylation mechanism. Key scientist concerns are that there not be too much focus on specific epigenetic mechanisms since epigenetics is cutting edge science (finding we do have more control over our genes then previously thought), there is a lot unknown, and the mechanisms now known may become outdated as the science progresses. [Marriott Portland State University, Powerpoint].
Pearl: Just learn the concept — That environmental factors influence epigenetics with consequent gene expression that makes the gene readable, or not. I ♥ this video from the University of Utah Genetic Science Learning Center, “The Epigenome at a Glance” video. It is interactive and allows you to wind and unwind genes as theirhistones and chemical tags epigenetically react to environmental signals from diet, toxins (air, water, food, topicals), stress, sleep, etc! The process whereby environmental factors influence gene expression is called “epigenetics.”
Source: biomeonboardawareness.com, Epigenetics
If you sequence the genomes of a pair of identical twins every decade for fifty years, you get the same sequence over and over. But if you sequence the epigenomes of a pair of twins you find substantial differences: the pattern of epigenetic marks on the genomes of their various cells, virtually identical at the start of the experiment, diverges over time… It is a testament to the unsettling beauty of the genome that it can make the real world stick… Chance events—injuries, infections…, impinge on one twin and not on the other. Genes are turned on and off in response to these events, as epigenetic marks are gradually layered above genes, etching the genome with its own scars. [Mukherjee, 2016 New Yorker Magazine]
One of the main processes switching genes on and off is an epigenetic process known as DNA methylation. By controlling which genes are on or off in any given cell, we are able to grow kidneys, heart, skin, etc. and control how these cells behave and what they look like. How Does Genetics Explain Non-identical identical twins?
“Methylation is [one] common and widely used mechanism for epigenetic modifications in cells.In methylation, methyl groups (CH3) stick to DNA and usually suppress gene expression. Histones are the proteins DNA is wrapped tightly around. Histone modifications [are another mechanism that] usually involve attachment of an acetyl group (CH3CO.) Acetylation helps tightly coiled DNA unwind a bit, making genes easier to get to and turn on.” [Moosav et al 2016]
Environmental exposuresalter the expression of genes by tightly wrapping them making them unreadable (aka the gene is turned OFF), or relaxing genes so that the gene is easily accessible for attachment to chemical tags on the histone (aka gene is turned ON),thereby altering the mRNA and protein production.Proteins perform important functions for the cells. To function correctly, each cell depends on thousands of proteins to do their jobs in the right places at the right times. Epigenetics does not change the DNA, it reads the DNA differently and alters protein production which alters cell behavior and function. [Wopereis et al 2014]
I ♥ this analogy: The methyl groups hang off the DNA string like Christmas ornaments, and specific proteins add and remove the ornaments, in effect “decorating” the genome. The most heavily methylated parts of the genome tend to be dampened in their activity. [Mukherjee, 2016 New Yorker Magazine]
The cell epigenome is dynamic and can be affected by genetic and environmental factors. Furthermore, epigenetic modifications can be REVERSIBLE, which makes the genome flexible to respond to environment changes such as nutrition, stress, toxicity, exercise, and drugs[17]. [Moosav et al 2016]
Epigenetic changes can be transmitted to your children. It is our past, present, and future on disease risk — aka ‘developmental origin of health and disease’ (DOHaD)…Individuals with metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease may show a LIFETIME imbalance between energy intake and expenditure due to incorrect epigenetic programming during their EARLY developmentas a result of placental insufficiency, inadequate maternal nutrition, metabolic disturbances, or neonatal medication.[Szarc vel Szic et al 2015]
Epigenetics What Makes You You? https://podcasts.ox.ac.uk/epigenetics-what-makes-you-you
Food as Epigenetic Medicine: The next challenge is to determine which adverse epigenomic disease marks are reversible by specific diets, lifestyle changes, or drugs.
But you don’t need to wait for the researchers. What do you have to lose? Just try the tenets of Therapeutic Diets because…
MANY diseases have altered epigenetic methylation including (not exhaustive listing):
Different cancers, autoimmune disorders, neurological disorders including Fragile X syndrome, Huntington, Alzheimer, and Parkinsondiseases and schizophrenia. [Moosav et al 2016]
Asthma. Over two dozen genes regulate the antibody IgE which provokes allergic reactions… the epigenetic mechanism of low methylation occurring at 36 places in 34 genes. This mechanism, low methylation. meant the genes didn’t get turned off so there was overproduction of IgE antibodies that trigger asthma attacks. [Liang et al 2015].
Brain Disorders and Neurodegeneration.A high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration…This paper integrates evidence from the disparate fields of gastroenterology and neuroscience tohypothesize that gut bacteria ferment fiber to produce butyrate, a short-chain fatty acid (SCFA), that can alter gene expression in the brain to improve brain health. See below, Fig. 2. The proposed mechanisms for the neuroprotective effects of butyrate and the diseases [Alzheimer’s, Parkinson’s, Huntington’s, Mitochondrial Encephalopathy, Adrenoleuko-dystrophy, metabolic disorders, insulin resistance in brain, stroke, autism, psychological disorders] which may benefit from butyrate treatment or a high fiber diet. We can no longer overlook the importance of the gut-brain axis and nutrition in disease pathogenesis and treatment. [Bourass et al, 2016].
Chronic Fatigue Syndrome. 1,192 CpG sites were identified as differentially methylated between CFS patients and healthy control subjects, corresponding to 826 genes.[Wilfred C. de Vega et al 2014]. Parkinson’s [Miranda-Morales et al 2017]. ALS.This study found widespread changes in methylation patterns in ALS-affected co-twins, consistent with an epigenetic contribution to disease.[Young et al 2017]. Colon and other Cancers. Butyrate can modify histones which in turn can regulate the expression of miRNAs in colon and other cancers. [Bishop et al 2017]. As cells become malignant, or cancerous, epigenetic modifications can deactivate tumour suppressor genes, which prevent excessive cell proliferation [Esteller, 2007].
DIET can Modulate Epigenetics by changing the Microbiome to Increase Production of Butyrate:
It is estimated that 90% of the cells in the human body are of microbial origin, and the vast majority of these microbiota are comprised of 15,000–36,000 species of commensal and symbiotic bacteria that reside within the lumen of the gut.[Frank et all 2007] [Stillling et al 2014].
The microbiota produce metabolites which include short-chain fatty acids (the most common are propionate, acetate and butyrate — butyrate is an important source of energy for colonic epithelial cells, may enhance epithelial barrier integrity, modulate the GI immune response, produce neurotransmitters (serotonin, dopamine, and GABA),alter epigenetic markers, and produce bioactive food components and energy metabolites. Some microbe-derived metabolites enter the circulation and can cross the blood-brain barrier. =&1=&Butyrate biological functions include its ability to serve as a histone deacetylase (HDAC) inhibitor [epigenetic mechanism], an energy metabolite to produce ATP and a G protein-coupled receptor (GPCR) activator.[Frank et all 2007]
♥ Certain Microbiota can produce butyrate: 2 major groups of butyrate-producing bacteria are Faecalibacterium prausnitzii and Eubacterium rectale/Roseburia spp. [Bishop et al 2017]
♥ In addition to microbiota production of butyrate, diet can influence the production of butyrate (see pic below for relative proportions of SCFAs for various carbs).
“Much attention is currently focused on the modulation of hyper/hypomethylation of key inflammatory genes by dietary factors as an effective approach to chronic inflammatory disease management and general health benefits. In this respect, ‘Let food be your epigenetic medicine’ could represent a novel interpretation of what Hippocrates said twenty-five centuries ago.” [Szarc vel Szic et al 2015]
SUMMARY: Why Must You Understand Epigenetics? Because epigenetics is the real driver of your health status, and diet plays a major role in gene expression (aka epigenetics), at least in this post’s animal study!Mention this fun fact at holiday gatherings as others notice and comment — good and bad — about your favor of healthy whole foods with resist of the nutritionally empty and microbiome harming options! Epigenetics is a big word but it simply means the process by which your genes are turned on or off (aka expressed) in good or bad ways. You already know, diet pre-selects “who” comprises the gut microbiome. This post shares the University of Wisconsin-Madison mouse studywhich found that themolecules produced by the microbiome (aka metabolites) tells our genes what to do (turn on or off). This study looked at two diets: a carbohydrate rich diet (one rich in plant carbohydrates similar to fruits and vegetables humans consume) and pitted it against the Western, Standard American Diet (SAD) (think high in simple refined carbs, added sugars, and unhealthy fats — this is found in most all home cooked, grocery prepared, and restaurant meals as they use convenient processed ingredients). Their results showed the plant based diet yielded a more rich microbiome which in turn, produced metabolites that seemed to favor host-microbe communication as they chemically communicated with cells, including cells FAR beyond the colon (the liver and white fat tissue), to dictate gene expression and health (metabolic — insulin, lipid to name a few) in its host.In contrast, the metabolites of the SAD did not provide this communication likely because it was MISSING the necessary metabolites to do so! If you think this is awkward party talk, what is even MORE AWKWARD is feeling others watch what you eat so that they can learn what foods express their genes best! You’ve worked hard to learn microbiome. I am in awe and proud of you. Now it’s your turn to pay it forward and teach others by doing!
Look… Your genes are not your destiny. Disease is rooted in our DNA EXPRESSION.
Epigenetics triggers disease in those predisposed.
Time to learn a short EASY bit more about epigenetics now that you know THIS is the real driver of your health status.
I love this video analogy of epigenetics: “What is Epigenetics? An Entertaining and Educational Primer”,GreenmedTV, April 2013. Look through the below slides to see how they use only PUNCTUATION VARIANCE TO DRAMATICALLY CHANGE UP THE DIALOGUE CONTEXT. This is a great analogy to what epigenetics does. EPIGENETICS DOES NOT “CHANGE UP” HUMAN DNA — that is constant for a lifetime. Rather, anEPIGENETIC CHANGE READS THE INFORMATION DIFFERENTLY AND EXPRESSES GENES ACCORDINGLY; THAT CAN BE BENEFICIAL OR DETRIMENTAL TO HEALTH AND DISEASE STATUS. I want you to think of this analogy as you read through the short EASY technicals of epigenetics because epigenetics is easier to get than it sounds! Here’s the bottom line: “Interactions with the environment do not change the genes, but they alter their expression by switching them on and off through chemical tags on the DNA“.— Gut microbes switch host genes on and off under influence of diet
Now for the technicals made EASY and simple:A module from Learning Genetics, from the University of Utah, called The Epigenome at a Glanceexplains:
DNA contains the instructions for building all the parts of the body. DNA is wrapped around proteins called histones. Both the DNA and histones are covered with chemical tags. This second layer of structure is called the epigenome. See this in the below slide.
The epigenome shapes the physical structure of the genome. It tightly wraps inactive genes making them unreadable. It relaxes active genes making them easily accessible. Different genes are active in different cell types. The human DNA code is fixed for life, but the epigenome is flexible.
The epigenome changes in response to signals. Signals come from inside the cell, from neighboring cells, or from the outside world (environment). The signals from the outside world or environment that epigenetic tags react to include diet (things we eat are broken down and circulate throughout the body), stress (physical, emotional, chronic inflammation, disease), sleep, toxins, and more (see parameters on the below Whole Health Pillars slide). The epigenome adjusts specific genes in our genometic landscape in response to our rapidly changing environment.
It is Proteins that Carry the Signals to the DNA. Once a signal reaches a cell, proteins carry information inside. Like runners in a relay race, proteins pass information to one another. The specifics of the proteins involved and how they work differ, depending on the signal and the cell type. But the basic idea is universal. The information is ultimately passed to a gene regulatory protein that attaches to a specific sequence of letters on the DNA.
A gene regulatory protein attaches to a specific sequence of DNA on one or more genes. Once there, it acts like a switch, activating genes or shutting them down. Gene regulatory proteins also recruit enzymes that add or remove epigenetic tags. Enzymes add epigenetic tags to the DNA, the histones, or both. Epigenetic tags give the cell a way to “remember” long-term what its genes should be doing.
The PEARL: Signals from the outside world can work through the epigenome to change a cell’s gene expression, moving towards health, or not.
Now for the University of Wisconsin-Madison diet study.
The study, Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues, withfull text PDF here,found that gut microbes have a huge role in health as they alter the host gene expression in a diet dependent manner. The two diets studied, a plant based carbohydrate rich diet (think fruit/vegetables) compared to the Western, Standard American Diet (SAD) (think low fiber and high in simple carbs, sugars, and unhealthy fats found in most all home cooked/grocery prepared/restaurant foods as they use processed ingredients),expressed genes very differently not just in the gut, but in the liver and fatty tissue FAR removed from the gut.From the Wisconsin University News article,Gut’s microbial community shown to influence host gene expression:
The Grim Disease Incidence Stats: If you don’t have chronic disease now, you likely will, & sooner than you may expect.
Look… Your genes are not your destiny. Disease is rooted in our DNA EXPRESSION.