How epigenetics, our gut microbiome and the environment interact to change our lives

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There’s been increasing media coverage recently harkening back to Lamarck and inheritance of genetic code that changes in response to the environment (epigenetics).

”Lamarckism” as it came to be called was eschewed for more than a hundred years after its initial proposition because it was thought that genes were static (this reminds me of how Einstein originally developed a model which required an expanding universe, then he added a coefficient (the ‘Cosmological Constant’) to return its behavior to a static state, which later in hindsight was found to be wrong). Now it appears Lamarck while overstating the plasticity of genes, was on to something.

Epigenetics suggests that our genes are constantly in a state of flux, exposed and changing in response to environmental factors. But are these changes indeed heritable? Currently, there isn’t yet consensus that environment, epigenetics, and inheritance intersect or a valid theory for how genes behave in organisms. But now that Lamarckism is back in the public’s vernacular there will be countless studies performed to support or refute the thesis.

Screen Shot 2014-04-15 at 10.33.54 AMResearch presented at the American Association for the Advancement of Science 2014 conference supported some conjecture that epigenetics and some form of heritability are in fact linked. That suggests that much of our lives and life trajectories could, in fact, reflect a sensitive interplay between our environment, genes (epigenetics) and microbiome, as in illustrated in the Venn diagram, in which the intersection of all of these factors is, quite simply, ‘us.’

The proposed Venn of the interplay of our environment, adaptable genes, and microbiome. At the center intersection: Us.

External environment

We are influenced by external factors (sunlight, environmental toxins, stress, temperature, etc.), all of which can, to varying degrees, alter our genes. I’ve already explained in another article how something as simple as grapefruit can downregulate (inhibit the activity of) enzymes produced by our genes, making it more likely that the external environment will interact with our body; grapefruits interact with more than 90 drugs because of this effect. It’s also been shown that the ultraviolet part of the spectrum in sunlight causes physical changes in cellular DNA, which can lead to skin cancer.DNA_UV_damage

We also know of chemicals and drugs that have teratogenic (can disturb the development of an embryo or fetus) properties. A Lancet study from 2012 showed that 510,000 deaths occurred worldwide as a result of congenital disorders. Therefore, we know of many external mechanisms and their impact on our body, potentially through epigenetic means. The penultimate forerunner of epigenetics is the Hygiene Hypothesis, which states that a lack of early exposure to foreign bodies (bacteria, viruses, parasites, allergens, etc.) is associated with a dysregulated (i.e., not functioning normally) immune system.

Microbiome

News coverage has flirted with the topic of digestive microbiome (euphemistically called ‘gut health’ or similar). What I read is often misquoted from the research literature, ‘extrapolated’ and generalized beyond the study data and littered with anecdotes. What IS clear is that we are, on average, too clean.post-2282-Human-Microbiome-Project-Decod-YCSc

The microbiome usually refers to the flora that colonizes our digestive systems. I specifically didn’t refer to this (logically enough) as the ‘internal environment.’ Why? Here’s the reality to our ‘internal’ and ‘external’ environments: The human body has developed in such a way that the alimentary canal (digestive system) forms a path through the body. In this way, the body basically envelops the space that is the alimentary system; therefore your digestive system is outside of your body. Let’s think about that again: Inside your digestive system is outside of your body. Your body accesses nutrients through digestion from food passing through, but these nutrients pass through your intestinal walls, and your body is separated from the food by many layers of cellular lamina; the food is outside of your body. By contrast, those things inside of your body, such as organs, blood, etc. are designed to be axenic – this term means ‘free from foreign bodies.’ If you weren’t axenic, that would mean that you had an active infection.

A significant portion of this is the microbiome of the gut. There is an incredible, largely invisible world, of cellular communication, symbiosis and chemistry occurring between ‘us’ and our microbiome. Strictly speaking, we could consider these organisms to be ‘outside’ of our body, based on what I described earlier. But either way make no mistake: Without our intestinal flora, we would not survive. They are part (a large part) of our immune system, they help digest food, they keep us free from illness by out-competing foreign pathogens (by producing bacteriocins, fatty acids, and clocking prevent pathogen implantation).

Our intestinal colonies have also been targeted for study because of how they make antioxidants in cocoa available for our bodies to use. A meta-analysis (a study of studies) of 20 research papers showed a meaningful drop in blood pressure in those who consumed dark chocolate or cocoa daily; this is a direct result of the fermentation and further digestion of these compounds made possible by our microbiome.

How Do These Three Pieces Interact?

As shown in the Venn diagram, there is a circularity here. Each of the elements influences the other: Our environment provides the stimulus for epigenetics; our microbiome influences epigenetics; our environment affects our microbiome.

Some novel research indicates that certain compounds produced by certain gut flora can make colon cancer more prevalent by blocking the activity of DNA repair proteins. And that may not be just something for ‘someone else’ to worry about; another recent finding published in Nature shows that the composition of the gut microflora can be changed very ‘rapidly and reproducibly’ in response to dietary changes. Some of the consequences are directly due to microbial gene expression. This could be for the worse, but could of course also be for the better (reducing the odds of genetic changes and cancer).

Even the inflammatory cascade of Crohn’s disease seems to be related to the gut microbiome and specific microbes in particular. The researchers in this particular study even developed a model called a “microbial dysbiosis index” to predict Crohn’s disease onset and severity based on the flora present in study participants.

Fairly robust evidence exists to suggest that children raised in more rural areas (more exposure to animals, dirt, debris, molds, pollen, etc.) suffer from fewer cases of allergies than those children raised in more urban settings. Again, that pattern suggests an interplay of our external environment, microbiome, and epigenetics.

Ben Locwin, Ph.D., MBA, M.S. is a contributor to the Genetic Literacy Project and is an author of a wide variety of scientific articles for books and magazines. He is also a neuroscience researcher and consultant for many industries including food and nutrition, pharmaceutical, psychological, and academic. Follow him at @BenLocwin.

  • Hominid

    Epigenetics is the latest humanist pseudoscientific claim intended to diminish the well-established huge impact of genetics.

    • Evidence please? I’m as skeptical as anyone over the anti-science strain in humanism, but the evidence of epigenetic effects is overwhelming. What they MEAN is open to misuse and abuse by ideological factions, because of the data overload and the Black Box nature of epignetics…in other words effect does not equal impact in all cases–but it’s not like this is made up stuff.

      • Hominid

        Epigenetic ‘effects’ are not the issue – of course they’re real and have been recognized for decades. My own research was on differential gene regulation by external signals. The notion that such effects are transferred to gametes and determine phenotypes in subsequent generations is not only unproven, it doesn’t make physiological sense. It’s not up to me to provide ‘evidence’ to refute a positive claim that someone else has made – it’s up to the claimant to produce positive evidence of his claim. Try a little logic.

        • The question of whether it changes the germline is indeed unproven, but the guest author did not make that claim. As you suggest, anyone with a hint of knowledge of genetics knows how limited epigenetic effects are compared to genetic effects. If you’re interested, I’d welcome a guest article by you.

        • Ben L

          It seems like what Hominid is trying to say is that the current deluge of articles rushing to embrace a ‘feel-good’ theory (e.g., something ‘more humanistic’) de-emphasizes the good scientific work that has been done in genetics (including epigenetics.

          I think the Lamarckism bit has very little empiricity to stand on, but there’s certainly some evidence of this ‘echo’ effect. Here are a few:

          http://www.nature.com/nrg/journal/v7/n5/full/nrg1834.html

          http://www.nature.com/neuro/journal/v17/n1/full/nn.3594.html

          In these cases, the authors don’t purport to know why there are these relationships, just that they are present. So, for the moment, it’s empirical evidence in search of a supporting theory of mechanism (i.e., how would it work).

        • ESNYC80

          There is actually a logical method through which epigenetic factors could be transferred to gametes. Activated genes could preferentially be passed to gametes, increasing the odds that they are part of the genetic composition of the next generation. This wouldn’t really be epigenetics, per se, but it seems probable that evolution would have selected for this capability over time.

          • Hominid

            Deductive arguments are not a substitute for experimental evidence. Because something can be imagined doesn’t mean it exists.

          • Bibibibibib Blubb
          • Hominid

            Not relevant to the issue.

            Of course genes are impacted by extragenetic influences – that’s been known for decades and is, in fact, the theoretical framework for my own research. That’s not, however, the concept that the new ‘version’ of ‘epigenetics’ seeks to promote.

          • Bibibibibib Blubb

            “The notion that such effects are transferred to gametes and determine phenotypes in subsequent generations is not only unproven, it doesn’t make physiological sense.”

            Your main argument is that epigenetics cannot be transferred to new generations… which is false and has be proven true long ago and pretty much every few month since then. That link I posted has proven you wrong again. Period. There is no argument here. You either accept or you are delusional and cannot possibly be a proper scientist.

        • GwionB

          Thats the exciting part though, they are transferred across the generational gap! At least in some cases. The patterns of DNA methylation for example which are influenced by a variety of environmental factors, are heritable, because the same molecular machinery that replicates nucleotides during gametogenesis replicate the CpG methylation too, hence the methylation pattern of the parent is preserved and passed on to the offspring. Several studies have suggested this; the case of the isolated Swedish community Overkalix (I wont overload the post here with a case study but google it if youre not familiar), similarly with the children/grandchildren of pacific islanders who starved, who themselves have fast foods etc available are far more prone to obesity and the associated effects due to heritable epigenetic changes passed on by their starving parents/grandparents to “grab hold to all those lipids etc you find”, physiologically speaking. I’m only a 3rd yr undergrad but it seems to me to be an added layer of complexity an control that allows our genome to react in large ways in the short term by changing expression patterns, and its perfectly sensible to suggest they could be inherited. In fact at least some of the evidence that it is, is there! 🙂

          • Hominid

            Replication of methylated DNA during gametogenesis ONLY occurs if the epigenetic effect is on the gamete precursors, not when it is on somatic cells – where the overwhelming bulk of epigenetic effects occur. There is no known physiological mechanism whereby methylations in somatic tissues are transferrable to gamete precursor cells.

            Moreover, methylation is corrected by DNA repair mechanisms. It cannot be sustained across generations.

            The studies you refer to are not conclusive. You’re talking about inferences of compatibility with a speculation, not conclusive evidence.

            Lamarckian epigenetics is what you get when pseudoscience is tolerated.

  • GwionB

    Lamark was somewhat off the target with his theories but modern genetics and evolutionary biology is proving that his ideas may not have been as mad as first imagined! Though there’s not a shred of evidence of any “inheritance of acquired characteristics” in the way he imagined it, the heritability of DNA methylation patterns and epigenetic changes is becoming acknowledged in genetics, and and evidence for GxE (gene by environment) interactions and phenotypic plasticity in conditions of varying temperature, predation, food etc are extensive and well supported (though obviously in this case the potential for a range of phenotypes for a given genotype is passed on rather than any one acquired phenotype itself, still the notion of plasticity in this sense is Lamarkian in character). The man wasn’t entirely right but perhaps history will view him as unfairly mocked for all of these years.