Feed Your Microbes - Nurture Your Mind | John Cryan | TEDxHa'pennyBridge

Growing up in the west of Ireland, my grandmother lived with us, but it was only recently that I began to reflect on how it is that she lives so long and so well with all her cognitive faculties in place. Was it genetics? Well, longevity was hereditary in her family, but more so. Recently I started to think that there might be something more to it and I had a feeling that there was and one of the things my grandmother used to say is that long before it became a TV catchphrase, she said: you are what you eat, so Eat well. and in fact, the search for this Fountain of Youth is something that has fascinated humanity for millennia none other than the famous Russian immunologist Elie Metchnikoff, now Mexican, worked at the Pasteur Institute in Paris at the beginning of the last century and won a Nobel Prize for all his famous work in immunology, but as often happens to famous scientists later in their careers, they can start to have some crazy ideas and Metchnikoff had no shortage of these and one of his crazy ideas was why people in parts than what is now Bulgaria, why do they live longer?

And he attributed it to the fact that they ate a lot of fermented foods that contained lactic acid bacteria, so you are what you eat, but handcuffs work. He also hinted at something else, what if not? only what you eat, but you are what

your

microbes

eat and what is important to reinforce is that in the last two decades we have begun to really understand that there is a very important relationship between our

microbes

and our general physiology, but the first thing we really I want to reinforce is that we live in a microbial world, these trillions of bacteria that are inside of us and the honors are really shaping a lot of what we do, for example, in terms of genes, we are 99% microbial, it's quite humbling if If you think about all the money we've spent on the Human Genome Project, it's now less than 1% of our genes.

If I had given this talk eighteen months ago, I would have told you that we have 10 times more microbial cells than we do. human cells, but this is a very rapidly moving field with changes in technology and mathematical models happening all the time and so, more recently, this ten to one ratio has been reduced to one point three to one, so we're still more microbial, but almost So when you go to the bathroom and you get rid of some of these microbes, think of

your

self as becoming more human. We have recently been revisiting Metchnikoff's ideas and have shown that, for example, in aged animals there is a decline in the way this microbiome is functioning and that we can relate changes in the microbiome to cognitive decline and anxiety.

Furthermore, work by my colleagues in Cork has demonstrated a clear relationship in an older population between microbiome composition and diversity with health outcomes in older people with more diverse characteristics. Microbes have much better rates of frailty and cognitive health, so you are what you eat and you are what your microbes eat, and that would have been quite interesting, but the Cork researchers went a step further and showed that what was in they investigated what was in them. they promoted this diversity and noted it; It was actually the diversity of the diet of people who have a bland diet full of processed foods that was very repetitive and had a huge reduction in their microbiome, while those who have a much more diverse diet full of fruits. and vegetables have a much greater diversity in the microbiome so you are what your microbes eat and this will affect your overall health and one of the big questions we have in this field is how the microbes in your gut influence your health in so many ways and The main thing I want to convey today is that microbes are little factories that produce all kinds of weird and wonderful chemicals that our bodies would not produce without them and that these chemicals, depending on the foods eaten, can benefit really all aspects of health. so we can modify our diets or we can modify the microbes to shape this and there is perhaps no better example of this interaction between microbes and diets than breast milk in the early stages of life.

Human breast milk is unique among mammals in its complexity. contains many very specific sugars that are not present in cow's milk, for example, and we know that these sugars are very good for supporting gut health and immune function, but to me perhaps the most surprising thing is that the baby cannot digest these sugars. They are an exquisite example of coevolution, instead they are digested by microbes, so we know that the chemicals these microbes produce will support many different aspects of health, including brain development, and this is likely the basis for some of the beneficial effects. As seen with breast

feed

ing, another component of breast milk is fatty acids, and among fatty acids, you may have heard of omega three.

We have recently shown that omega-3 fatty acids can also affect the composition of your microbes and whether we deplete omega trees. and diets and animals we can really change the trajectory of brain development and behavior, so the health of your brain depends on what your microbes eat. Another dietary component that is getting a lot of attention is polyphenols, when I first heard about polyphenols. She sounded like some kind of '70s disco queen, but polyphenols are really important dietary substances that are most talked about, found in dark chocolate and red wine. What we are going to say is that they are also found in onions, grape juice and green tea, but polyphenols.

They have been shown to have really good anti-aging properties and also affect learning and memory and more recently it has been shown that many polyphenols are not actually absorbed, but rather reach the lower part of the intestine and act on them. by your microbes, plus polyphenols will affect the composition of these microbes, so again, you are what your microbes eat, so omega three polyphenols could we come up with a diet rich in these that might have some beneficial effects for our health? Well, we don't. You don't have to go too far and limit yourself to the Mediterranean: the Mediterranean diet has long been known to have beneficial effects on cardiovascular health and reduces the incidence of stroke, diabetes, obesity and heart disease, making it a truly Rich in both polyphenols and omega three.

And what about the Mediterranean diet and brain health? Just this year a study was published in Australia to show that adding a modified Mediterranean diet to regular psychotherapy or anti-depression medications was enough to have profound effects on mood, and these types of studies are marking the beginning. into a whole new discipline of nutritional psychiatry where we can address mental health through dietary means, in a way that goes back to Hippocrates where he said let food be our medicine and maybe the missing part of this puzzle is what is the role of microbes in mediating these positive effects and that is still to be resolved, but I really believe that they play a crucial role and why can I be so sure?

Well, it goes back to some of our studies in basic neuroscience that we have in animals and now we don't. You have to be a neuroscientist to see that when we take microbes out of a system, these are germ-free mice, they've never had microbes and these brains grow without microbes. intestinal, but you can clearly see that there are marked differences. in this nerve cell from the germ-free animal versus the control animal and we have shown that almost every aspect of brain health depends on having microbes in our gut, for example, in the last year we have shown that myelin myelin is the key isolation in which nerve cells communicate and that myelination is fully regulated by microbes in the gut, so if we can develop diets that target the microbiome to support brain health in crucial developmental windows, we can benefit many people and where is this.

What's going to be really important, for example, is in areas of severe malnutrition and malnutrition, like in sub-Saharan Africa, where there are many people with stunted growth, delayed cognitive decline and neurodevelopmental problems, so Many efforts are being made to try this. and develop strategies for this so far, everything I have told you has been about how diet affects our microbes, but could our microbes also affect our diets and food choices? That's something I find quite interesting and again this year a study emerged. from Lisbon, where they used a laboratory fruit fly to ask this, now fruit flies, madhu.

Give them a protein in their diet and give them a choice between yeast or sugar with yeast, since a fruit fly is like your steak, so if they are deprived of protein, they will immediately go after the yeast; However, if you put microbes into the situation, you can see that the animal no longer chooses protein or actually gravitates towards sugar as well and, if this could be shown in other species, it would have huge implications for our drive: we have to take certain foods and maybe later, the next time you crave that polyphenol-packed dark chocolate bar, maybe it's your microbes telling you to do it, one of the best ways we have to study.

Microbial diet interactions are looking at the microbes of some of our ancestors and scientists have gone out into the field and started to study what is happening in communities that maintain ancestral diets and, for example, in the hunting community -Hadza collectors and in Tanzania. We have shown that today having diets very rich in fiber is key in this sense and when they looked at their microbiome they could see a very, very diverse microbiome. Furthermore, we can trace the influence of the introduction of agriculture by looking at the microbiome and diets of people in rural Malawi and Venezuela and you can clearly see that it begins to decline in this microbiome and then in our Western world which What is seen is with the introduction of processed foods, sweeteners and emulsifiers, all of which are having a negative impact on the microbiome that we are more or less extinguishing the microbes that our ancestors had.

The intriguing part of this story is that if you look at diseases like multiple sclerosis, inflammatory bowel disease, diabetes, obesity, these are not present in these ancestral communities and a lot of interest is now being put into understanding the relationship that these missing microbes have at the origin of these diseases and we know little about what is happening in relation to brain health and the contribution of this depletion of microbes has two brain cells, but what we do know is that in the society in which We live in, in which increased stress and overuse of antibiotics, hypercleansing, a huge increase in cesarean births, all of which will affect the composition of the microbiome, that we are potentially having a public health problem in our midst and this it will also potentially affect our brain and how we deal with stress, but how do we deal with this and can we develop strategies to perhaps target the microbiome for mental health benefits and that brings us to the whole concept of a term that we coined in Cork psychobioethics and these are specific interventions that will focus on our microbiome to really promote brain health and to date, most of the studies with psychobiotics have been done only in the preclinical stage in animals, but little by little we are doing more and more around the world.

There is more and more work being done in the world to get evidence based on this completely new area and just paint your genome, you can, the genes that you received from your parents and grandparents, you can't do much with that, but your microbiome can potentially be modified through diet, prebiotics, probiotics and even fecal plans over time, so there is a slow psychobiotic revolution happening and changing the way we met could see the treatment of mental illnesses in the future, so, in Conclusion, I guess my advice is to always trust the words of an Irishman. Grandma eats well and maybe some of that wisdom comes from the trillions of bacteria inside your gut and I hope that gave you some food to throw away today.

Thank you so much.