Evolution, human-microbe interactions and the "epidemic" of inflammation-related disorders (alias: the hygiene hypothesis)

Published on July 31, 2016   31 min

Other Talks in the Series: Evolution and Medicine

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GRAHAM ROOK: Hello, my name is Graham Rook from University College, London. Today I'm going to talk about evolution, human microbe interactions, and the epidemic of inflammation-related disorders. The high income countries are facing massive increases in a whole range
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of chronic inflammatory disorders, and there's increasing evidence that this is at least partly due to changes in our contact with microorganisms. This notion was applied to allergies more than 25 years ago, and was at that time called "the hygiene hypothesis". But in this talk, I hope to demonstrate that our microbial contacts are indeed important, but that hygiene is not an important cause of our current problems. What we are seeing is an effect of other major lifestyle changes. In the high income countries, the immune system
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is attacking all kinds of things it should not attack. For instance, it's attacking the gut contents and the microbiota, the organisms that live in our guts. And this is contributing to inflammatory bowel disease like Crohn's disease and ulcerative colitis. Similarly, the immune system is attacking itself, attacking our own bodies, and this leads to autoimmune diseases like multiple sclerosis and Type 1 diabetes. Our immune systems are also attacking harmless molecules in air or food, and this gives rise to allergic disorders like asthma and eczema. And finally, the immune system is frequently maintaining inappropriate inflammation. Rather than simply turning on inflammation when there's some requirement for it, it leaves it on permanently. And permanent background inflammation predisposes us to psychiatric disorders, metabolic disorders, and cardiovascular disease. Now all of these things are happening, particularly, in high income countries more than low income countries, in urban rather than rural communities, and in people of low socioeconomic status more than those of high socioeconomic status. These increases are much too rapid to have
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been caused by genetic changes. Therefore, they must be due to environmental factors, which I will discuss. But of course, that does not mean that genes are not important, too. The bar on the left indicates the whole population, and the hatched area at the top is that small percentage of the population that would have had these chronic inflammatory disorders in the past. Now, those people still have the chronic inflammatory disorders now in the bar on the right. But some environmental changes occurred, represented by the paler hatching of the bar. And, that environmental change is causing a second population of people who are genetically susceptible to these disorders under these changed environmental conditions. And then finally, there is the group of people who are resistant to disease under past or present environmental conditions. Now, this is a classic example of gene by environment interactions. But what, then, is the relevant environmental change that is causing these changing disease patterns? To think about this, we have to go back into evolution.
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The vertebrates evolved about 500 million years ago. And vertebrates could be thought of as ecosystems. We very rapidly developed complex communities of microbial partners, which we call the microbiota, particularly the commensal organisms that live in our guts. Now, these organisms have become so important to our physiology that they are involved in development of most organ systems, including the brain. They are involved in sex hormone reuptake from the gut and modification of those hormones. They regulate the immune system. They regulate metabolism, diurnal rhythms, the so-called gut-brain axis, so they're modifying how the brain functions. And metabolites from small organisms make up perhaps 20% to 30% of all the small molecules in our peripheral blood. So, all the cells in our bodies are bathed in these small molecules. And we have very little understanding yet of what these molecules are doing. Now, in view of the enormous importance of this community of microbiota for our physiology, most evolutionary biologists think that the adaptive immune system evolved in order to manage or form the microbial partners. While performing this difficult balancing act of doing that while at the same time excluding dangerous pathogens. So, not only does the immune system modulate the microbial partners, but the microbial partners also modulate the immune system. But they don't do it alone. The so-called "old infections", which I will talk about later, also have important input into the way the immune system is regulated. And, so do other organisms and their genes from the natural environment. And some of us refer to these three groups of microorganisms, the microbiota, the "old infections", and the organisms from the natural environment, as old friends because they were with us throughout human evolution. Another way of looking at this is to say that the adaptive immune system
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Evolution, human-microbe interactions and the "epidemic" of inflammation-related disorders (alias: the hygiene hypothesis)

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