Gut Microbes and Mind Control: How to Fix Your Brain by Fixing Your Gut

[00:00:05]right well thank you anyway Rich for the introduction so as R said I'm going to try and inform you a little bit about what goes on in your gut and in particular all the microbes that live in your gut and why they're so important for your health and why under some conditions they can actually cause quite severe disease so there's been a significant shift in our understanding of what causes disease and I think you know traditionally we've always thought of it's to do with who we are our genes and then the things we do as we go through life so lifestyle and what we eat and what we get exposed to in the environment and it's those two that come together to either keep us healthy or to cause disease but what's apparent now is that in the middle of this and that may be involved in interpreting a lot of these things that we do eat are our gut microbes and they're are direct linked to our genetic material and they can in turn influence how we react and respond to things in the environment and how they can keep us healthy or or not and really the understanding of gut microbes has really taken a fantastic leap since around 2000 this graph here shows the number of scientific articles that have been published about gut microbes and you can see there they really started to take off here around 2002 and that's because of technology so before 2002 the only way we could really identify and characterize a gut microbes was by what we could culture on a petri dish and since we now know that about 80% of our gut microbes can't be cultured that really isn't a good representation of what's in our gut but then with the Advent of Gene sequencing technology we can now identify mic mes according to their genetic blueprint and what's apparent is that different types of bacteria have a unique genetic fingerprint so if we can identify the fingerprint we can say whether or not they're present or absent and this as I said has led to this huge explosion in this area of research we can now identify microbes that we cannot culture and so this has led to massive interest in gut microbes and some of these uh are very recent so the the daily mail um thinks healthy gut bacteria might be linked to anxiety and then we've got others that linking gut brain connection autism probiotics as a means of treating diseases and then a couple of books this one has just come out and those of you in the Institute will notice the significance of broccoli on the front as The Institute is responsible for generating strains of broccoli that have lots of um nutrients good beneficial nutrients in them um but really the message here is that what we eat influen inuences our microbes which in turn can influence our brain function and keeping it normal but as always we have to be aware of the hype okay so whenever we read these articles we need to have a couple of things in mind that allow us to determine whether or not you know there's some factual basis to it or whether it's hype and these are some of the questions that um I would say you need to ask so the obvious one is well so what do these differences they detected do they really matter are the changes a cause or a consequence of the disease and of course we want to know how it works what's the mechanism so is there anything in this article that allows us to understand how it actually works and then a lot of experiments are carried out on animals because we can't do many interventions in humans for ethical reasons so another obvious question is well is a mouse a small human no it isn't so we got to bear that in mind and then obviously we've got to think well is there something else they haven't looked at which could explain what they're describing so behavior and lifestyle are two important things so I'm going to try and sort of touch on some of these things in the rest of my talk so this is what I'm going to cover I think I need to introduce the gut to you uh I'll talk a little bit about microbes some interesting facts a little bit of trivia and then how gut microbes may play a role in determining what we eat and what the consequences of what we eat are for our health and well-being and then how we actually might manipulate theut microbes to improve or restore our health so that's what I call lawn care right to start with so the the gut mouth to the anus it's a long tube here's a picture taken with um an endoscope and you can see it's not a smooth tube it's got these ridges to it the muscles this this is what allows food to be propelled through the gut but it's not a smooth tube it has lots of finger-like projections that we call Villi that stick into the loomin to capture nutrients and absorb them so the tube is quite long it's about 9 M from mouth to anus and somebody um has taken the trouble of trying to calculate what the surface area of all these V are and the outcome of that is it's probably about the size of a badminton court so it's an incredibly large area and it has to be large in order to take up the nutrients that are in your diet to keep you healthy and then we also consider the process of digestion and the gut is in fact a massive bioreactor so we take in Foods plant material for examples and they're broken down first of all in the small intestine here where the small simple sugars are absorbed and then the larger more complex plant material that we eat in our diet passes is through into the large bowel or the colon where it's fermented and it's fermented by the bacteria that live in the colon and the end product of all of this is something called short chain fatty acids which are very important because they can provide about 5 to 15% of our daily energy requirements in some animals it's up to 30% so this has to be a very efficient process to Keep Us Alive basically and the enzymes that are responsible the proteins that digest these food um material and the polysaccharides now we only have about 20 genes in our whole genome that will allow that encode proteins that will break down these carbohydrates but one bacterial species this one in particular bacteroides has 260 and you think there are thousand species so that's a vast number of proteins that can digest the digest our food so the bacteria that live in our colon are ideally suited for processing our food and extracting the maximum level of nutrients from them so it's a bioreactor a little bit about the microbes so the gut is packed full of microbes there is no space that endoscope image I showed you they've displaced and rinsed out all the bacteria normally that would be jam-packed with bacteria most of them are floating free in the Lumen but a large number of them actually make physical contact with the cells that line our gut so there's actually some intimate Association of these microbes with our gut and there are two terms that we you may come across that we use to describe these microbes the microbiota which is to describe all the microorganisms that live in the gut and there there's the microbiome and that's all the microbes plus all their genes combined so microbiota micro biome two words you may have come across in a lot of these articles but individually bacteria incredibly small so this is the head of a pin under an electron microscope and each of these orange dots represents one bacterial cell so you can see that you can get lots of bacteria on the top on the tip of a pin they're incredibly small but where although they're small they make up for that in their vast numbers so we have about 10 ion cells in our body but we actually have 10 times that number of bacteria in our body and so on this scale here we have enough cells that would fill half of one of our legs all the rest of the body would be filled up with microbes bacteria and then if we think about all the DNA that we have oh this is an interesting quote sorry I forgot about this this an inter just to give you an idea of the scope and scale of the numbers here of bugs a bacteria in our colon so just one linear centimeter contains more bacteria than all the humans that have ever been born so it's a vast number of microbes and then the DNA elements this is the big toe okay and that represents the DNA in our body that is actually ours okay so everything else more than 99% of the DNA is bacterial DNA so you know just think about that that's actually quite amazing really so we are carrying around a lot of DNA but very a little of it is our own okay now this is the audient participation bit some trivia how much do you think all the microbes in our body weigh don't be shy PhD students at the back come on how much what uh stop conferring 16 so no anybody else kilogram closer k 2 kilog 2 to three kilog a lot right couple of bags sugar and if you put it in a volume size about 1 and a half liters and there's about a thousand different species thousand different types packed in there there and this is what they need to keep them healthy about 50 to 65 gr of these things which are sugars to keep them healthy so that amount is needed every day just to keep your microbes healthy and then you've got all the other things that you need to keep your body healthy and so a product of all this metabolism is gas so how much do you think we expel every day and this is everybody so it's not just old men and teenagers everybody in this room expels gas how much do you think we expel every day how many liters how many five no that's a bit High anybody else one to four that's a lot and of course at the end of all this we have waste so 60% of your stool is made up of bacteria live and dead Okay so that's trivia interesting thing just before you have your meal you can run through some of these facts of figures but they are very very important and we know they're very important because of animals that we can keep germ free so these are animals that have never been exposed to any microbes they're sterile and when we examine these animals they're clearly um compromised they're deficient so they have nutritional deficiencies they don't grow but interestingly they live longer so if you want to live longer don't eat that's the bottom line they have a defective gut so their gut is not po properly formed so it's leaky and their immune system is very poorly developed so they're very susceptible to infections and in fact if you introduce a pathogen to these animals it can kill them very quickly because they have no protection no immunity and also their development is affected as well so clearly we're already starting now to move into the gut brain so they there are really poor animals very sick so the microbiota and the mic microb are very important so your microbiota is unique to you it's your identity it's like your fingerprint your microbes are unique to you however ever the microbes you have are shared with other family members so there's some commonality there and interestingly looking at the microbiota of monozygotic and dizygotic that's identical non-identical twins you know there's no difference so even if you're an identical twin you'll have similar differences in your microbot to non-identical twins so what does that mean well it means that genes are important who you are is important but also the nurture the nature the nurturing is also important in shaping the microbes but we now know that we all have a core microbiota so there's about 57 species of bacteria that we all share and there are two types that predominate in all of us here and not unsurprisingly these are concered because they perform important functions such as ones here degradation of carbohydrates they degrading our plant material we eat they also provide these fatty acids that we need to Keep Us Alive every day and also amino acids and vitamins which we can't produce but our gut bacteria can so it's not surprising there's a core that all of us need to keep us healthy but then everything else all the other 800 or 2,000 species are all unique to us so where do they come from well your parents and particular for your mother so if you think you have bad bacteria you can blame your parents fully Justified okay now originally it was thought that we were born sterile but that's changing slightly is now evidence that we can in fact uh babies do get exposed in the womb to bacteria that the mother has and that can be through the placenta and also VI other Roots but by far the biggest source or time point at which you get exposed to microbes is soon after birth because if you believe we are born sterile then the bacteria can colonize very very quickly so the first few months after birth you're rapidly being colonized by bacteria the types of bacteria depend on the delivery so if it's vaginal delivery then most of the microbes that will colonize the baby will come from the mother if it's a C-section then the bacteria actually come from the people in the operating the that are handling the baby and most of those will be skin type bacteria and that's important because there are now evidence that links um later onset of various diseases and disorders back to whether or not you were vaginally born or from a C-section and the types of microbes that initially colonized your body other things that will impact on the types of microbes that will colonize this infant are delivery so is a normal birth or is it uh does it require intensive care the age at Birth is also important is it a full-term birth or pre-term birth and hygiene obviously where you're born the home versus the hospital have very different population of microbes that can colonize the infant and then after that things that will impact and cause alterations in the microbes are antibiotics and again it depends on how many what types and for how long and also very important is nutrition whether or not the infant's breast or bottle fed and again the breast milk contains lots of ingredients including microbes which can colonize the baby and keep them healthy but as we go older we get exposed to microbes from other sources and by different Roots so via the nose and lungs we breathe microbes in the mouth and the gut obviously the things we eat and through the skin and these are the sources so water and the food we eat will contain microbes if we have pets if we live on a farm we're getting exposed to different microbes from the animals that we live with where we live do we live in the country or do we live in the city the population of microbes again are very different and then the type of accommodation or the dwelling that you live in you know is it single dwelling is it multi- dwelling all these people are contributing microbes that will um you'll be exposed to and then are you indoors are you Outdoors are you active are you inactive are you an Xbox fan or are you out playing football these things will all expose different types of microbes all of these are important because Beyond three years of age your microbiota is pretty much set for life so the early years of life are critical for the development of a healthy microbiota however there are cultural things and social things that will also impact on the types of microbes that that um populat us now here's a fact most of you probably didn't know okay interesting one to to experiment on so intimacy and you know it's across the animal kingdom different types of intimacy transfer of microbes grooming it's another one nurturing food sharing right we often sit down at the table and eat together and we can be sharing food it's a good way of transferring microbes and then there's something that's slightly less you know pleasant but animals do transfer microbes to their offspring via this route by regurgitation of food and transfer of food as well as microbes so the message here is if you have some good bacteria you need to share it because there are some of us poor less fortunate people scientists for one right I mean my wife is very fond of telling me I have very little culture so maybe my culture is my bacteria so share your good bacteria if you have them right so we have our microbiota we've been exposed we've got a stable population but it's not the end of the story They do change and here we've got a representation of a aging so here you can see these circles the different colors represent different types of microbes as we age you can see the colors change as the populations change and there are some differences between formula fed and breastfed babies transition to solid food is a big one in terms of shifts in microbial populations and then you can see as we age um there is and also a shift as well in the population aging has an impact in itself but one of the most striking impacts is through antibiotic treatment and this slide just illustrates the impact of antibi two antibiotics to treat clostridium deosil which is a severe infection that is often acquired in hospital so as a result of the outgrowth of this bacteria we get sick so we're administered bomin or metronidazol and what you can see is the diversity the number of bacteria we have in our gut is drastically reduced because the antibiotics have killed them off but it's also killed off Clum deficit which is a good thing but you know there's a consequence to this in that we've wiped out a lot of our good bacteria so too many antibiotics for too long have a very profound and can be a longlived effect on our microbiota so antibiotics could be described as a man-made catastrophy however most of the antibiotics that are used are used in agriculture and in farm animals in particular to check infection accelerate growth so about 19,000 tons of antibiotics are used in agriculture every year and of course antibiotics get excreted by animals and humans as well so they can contaminate streams and rivers and then get back into the food chain and also giving antibiotics to children has its consequences as well so in the US by two years of age most children had at least three cses of antibiotics I know there's a phenomenal number of doses of antibiotics given out in the US and what this does is it drives bacteria to become resistant and this is serious okay so this particular organism here MSA now is resistant to most of the antibiotics that we have in the pharmacy and more than 19,000 people a year in the US are killed which is much higher than number of people dying from AIDS I don't know if you just seen on the news today but there's a UK government um review group has recommended the pharmaceutical industry invest $2 billion in developing new antibiotics there's a real need for this but one of the causes is that we administer too many antibiotics we take too many antibiotics it leads to resistance cautionary taale the other side of the story is that gut microbes can actually work on drugs rather than being affected by drugs they can also work on drugs the thing to bear in mind is that the vast majority of drugs we take are given orally and so the microbes in the gut can actually alter the drugs they can alter their structure they can produce factors that interfere with the drugs and they can alter how the body reacts to the drugs and here are some examples so the bad ones are these drugs here which are pencils anti-cancer drugs drugs used to control high blood pressure in certain individuals that have certain of microbes administering of these drugs will lead to increased toxicity and with some antibiotics as well there's a similar story but there's a good side to this as well in that gut microbes can process drugs to make them more active more efficacious such as this antibiotic here and this anti-inflammatory drug so what this means is that how you react to a drug can depend on the type of microbes you have in your gut and one of the things that medicine is heading towards perhaps is being able to administer or prescribe you a drug based on the population of microbes in your gut because there's no point in giving you a drug that your microbes will make toxic you want microbes to actually help the drugs become better for you more efficacious so this is what's been called personalized medicine the drugs will be given to you because you have been determined to to respond best to those drugs so then that brings me to really the the meat of my talk here in a way and this is what I'm going to try and persuade you of that your gut microbes can now influence what you eat when you eat and what happens when you do eat and so I formulated this hypothesis that gut microbes influence their hosts food choices and I've sort of put up three predictions in order to prove the hypothesis could be correct the first one is that the microbes you have in your gut is a consequence of the food that you eat and how you behave in the environment so this interesting so it's not a map of the galaxies it's actually the results of screening the the microbiomes in a lots of different animals and this is sort of a zoo collection each dot represents similar microbiotas in populations of animals and the lines of Separation here indicate how similar or related they are to other microbiote in other animals so we've got these sequences we know all the micros and this is how they all cluster so you can see different clusters so horses and rhinos are up here in their own little cluster ruminants such as sheep and cows make their own cluster elephants have their own little grouping up here and then we have the carnivores the lions and bears again they're a different cluster in red and then we have Lea feating monkeys so vegetarian monkeys and pigs and then the other primates humans include we're here so we're separate from the leaf eating monkeys so what does this mean well it means that who we are and what we eat determines heavily influences the microbes that populate our gut and that's reinforced by this study in looking at the microbes that are present in the gut of people that live in Bina Faso in Africa that have a rural diet primarily vegetarian based diet and Europeans and this is actually Italians have a western diet you can see just looking at the colors they're very different okay and what's interesting is if the people in Africa migrate to Europe to Italy and then adopt the Western diet they lose this and become this distribution of microbes so they haven't changed in terms of their genes or anything all they've done is their diet's changed and it's caused this profound shift in the microbes so the diet really is a driving force in making up the microbes that you have in your gut here's another example this is a Burmese python so they go through periods of fasting and then feasting I'm just looking at three different types of bacteria in the fast ing State you can see very low levels but if they're given a meal you know within half an hour you can see these striking shifts and expansions and increases in certain types of bacteria and these will eventually stabilize and then as the animal goes back into a fasting State they will decline again so fasting reduces the overall diversity and then feasting expands the diversity in response to diet so quite striking so that's diet stress is another thing we have to cope with in our environment and this is some evidence that links stress impacting on our gut microbes so nor adrenaline nor epinephrine and epine which are part of adrenaline are produced in response to stress and that can have a a direct effect on the bacteria that live in our gut and it can cause the outgrowth of particular types of bacteria so here for examp example 10,000 fold increase in growth in response to Adrenaline it's produced under stress and surgery is a stress and this bacteria here rapidly expands following surgery and if it's not contained then it can cause sepsis and mice that get exposed to a type of stress rapidly change their microbial populations and that's just shown here so these are normal animals see most of the bacteria little um circular shap shapes but then under food deprivation which is a form of stress you know they rapidly change the rod shaped bacteria and that was observed over 40 years ago so we've known for a while that stress is a major factor and then what's interesting is that probiotic bacteria that are present in some of these um Health Foods here's one from Morrison's and this is ACL they contain bacteria that produce a neurotransmitter gas gab and gaba's normally produced in the body what it does is it dampens down excitable neurons so it relaxes you so and this has been used by the pharmaceutical industry to develop mimics of gamma so they can overstimulate these receptors to make you even more relaxed and in fact even knock you out because anesthetics can work by mimicking the gabber that is produced by these bacteria so benzo diip Pines alcohol right we all feel nice and relaxed after a glass of wine or a bottle of beer well you know one of the wings that comes that about is that they're stimulating these receptors that gut bacteria can do as well so the gut bacteria can already you know hopefully take us from a stressful state to a relaxed St State and so one of the other things I wanted to highlight here was this obesity lots of of evidence in the literature now and in the newspapers that uh changes in our gut microbes to make can make us obese so gut microbes and obesity so very this is a very interesting experiment it's probably the best experiment that demonstrates how microbes can influence um whether or not we are be so lean so here we have identical twins but one of the twins is obese and one is lean so we've taken the stool sample from each of these extracted the bacteria what we've done is we put them into mice the mice are then put on a regular diet lowfat high carbohydrate I mean lowfat high fiber diet the ones that got the M got microbes from the obese twin become obese but the mice that got the microbes from the lean twin stay lean so that's a direct causal link okay so that's not really height that's a bit more closer to fact so of course it's mice it's not humans but this is the best evidence we have to date that shows a direct causal link between our gut microbes influencing whether or not we stay lean or whether we become obese and then this was in the Sunday Times this week uh this is from a study carried out by um Tim Spectre at Kings Coast London and he fed his son I don't know if his son was a willing volunteer a high fat diet for 10 days Big Macs and lots of of coke um and then he was taking stol samples before and after the the 10day diet what H what he showed was that first of all there was a reduction in nutrients because he's now eating this very processed refined Foods there was a loss in number of his got microbes but he gained 2 kilos in weight in just 10 days so the interpretation of this is that highly processed foods present in Big Mac containing ingredi of toxic to certain microbes and this leads to a loss of diversity we're losing microbes because of this and if you want to know more this individual has produced this book um I had nothing to do this so I'm not going buy it or anything but if you want to know more these books here so loss of diversity is a recurring theme and in fact I've already said in aging we have this loss of diversity we lose richness we lose microbes the same in obesity and it's the same in other disease particularly inflammatory bowel disease and cronon's disease so the loss of diversity in the types of micros have I got is not good it can have quite profound health effects and so it's not just got diseases all of these diseases shown here are linked by a common theme in a change or shift in the population of microbes in the gut and generally that shift means less diversity interestingly quite a few are linked with diseases of the central nervous system neurodegenerative diseases the heart the liver uh fat and rheumatoid arthritis there's lots and this is not a complete list by any means so obviously well is there one microb or one population of microbes that can cause the diseases so it's like looking for Waldo found him yeah there he is the only problem is there are lots of Waldos and so it's probably not one microbe it's the combination of microbes that when they get together you know it's a bit like a gang of teenagers you know they can be Rowdy or they can be miserable and antisocial um so it's the population when they come together that they causes or is probably responsible for the effects on our health it's not one it's probably Lots okay so moving on to the predictions we're now at the second one so gut bacteria can by influencing how our body works influence our appetite and food preferences so I'm sure this is a familiar scenario for many of you you know our mind says no take the healthy option but there's something inside of it say no I really like that piece of cake okay and it's maybe that gut feeling you know know I really am hungry for a piece of pie rather than an Apple so what is the evidence that normal gut microbes can influence brain development and behavior because that's what we're talking about brain development and behavior so this is an ex this is a summary of an experiment carried out a few years ago looking at our germfree mice again these are sterile mice and mice that have population got microbes this here shows the expression of an anxiety related Gene so the yellow identifies high levels in the brains of these mice that have got microbes but very little expression in germ free mice and this maze here is a measurement of how curious adventurous mice are so if they're cautious timid they'll spend most of their time in the enclosed section away from the lights but if they're adventurous like this one you know they'll be on the Open Arms so what this study showed was that gut microbes can affect normal brain development and make these mice more um curious um sorry wrong way and perhaps more creative and trying to escape so it's this fear Extinction you have got microbes you become a little bit more cautious reticent a little bit more anxious if you don't have got microbes you know it's the Great Escape you're looking for ways out more striking experiment is this one shown here so we've got two strains of mice what we'll call timid and adventurous so did got microbs have anything to do with why these animals are timid or adventurous so what we did so not what we did this group in Canada did was they took the stool from the timid Mouse isolated the microbes and put it into an adventurous Mouse and that Mouse became timid the other way around they took the microbes from an adventurous Mouse put it into a timid Mouse and these are ger free so they're an empty vessel that you can put the microbes into and they became now adventurers so this is a direct causal link again showing the gut microbes can influence the behavior of mice at least now is this translatable to humans I can see probably some people in the thinking maybe I could give this to my husband you know would he still be a grumpy old man if I gave him some microbes and would you know if my teenage boy had some microbes from you know somebody maybe they' become bit more outgoing bit more social maybe maybe a few years from now maybe I'll have that but not just yet but I mean we really shouldn't be too surprised by this because we now know that the the gut actually contains an awful lot of the neurons neural circuitry that's present in the brain and it's often thought to be the second brain I mean it has a very large number of neurons 500 million and it produces lots of neurotransmitters and you know here's some sort of evidence that sort of links the gut to the brain so brain dead people their stomach functions normally for quite a while it's almost an inherent activity anybody that's taken pain major painkilling drugs like morphine for example you know there's a risk of constipation it shuts down motility in your gut and emotions and feeling are intimately associated with bowel function right we've all had their butterflies in the stomach that nervous gut reaction well that's all those neurons in your gut that are firing away and when you look at the structure of the nerves in the gut that make up the interc nervous system you know these are the neurons or the dendrites here in silver the white color this is our gut tissue and you can see that when we superimpose these two the Nerf FIB is actually penetrate and intermix between all our gut tissue and they actually look like they're actually protruding into the Lumin to be able to sense perhaps the presence of factors that they can respond to that are in the gut Lumin that could be made by gut microbes and the vagus nerve is ultimately this the route by which all this signaling in the gut leads into the brain so all these signals here that these that the enteric nervous system responds to are fed into the brain via the vagus [Music] nerve and so we know that if the vagus nerve is blocked or damaged through injury profound effect on appetite and um eating in fact it causes drastic weight loss so it's clearly a regulator of body weight and vagus nerve stimulation by hormones and Ne neurotransmitters in the gut can drive excessive eating Behavior so over stimulation is not necessarily a good thing and not surprisingly gut microbes can actually regulate how much of these neurotransmitter and hormones are produced in the gut and they can manipulate this to their own Advantage by producing things that can block or stimulate the nerves in the syst in the gut so microbes control eating Behavior by influence signals that are delivered to the brain and by the vagus nerve and two of the most important are dopamine and serotonin so dopamine Associated rewards pleasure compulsions serotonin regulates our mood our memory sleep cognition dopamine about half of the amount of dopamine produced in the body is produced in the gut and some gut microbes can produce vast amounts of dopamine and some of you may know that L dopamine is used to treat Parkinson's disease serotonin is even more striking because virtually all the serotonin in the body is made in the gut and gut microbes produce factors that can mimic or block serotonin action in the gut and deficiency of Serotonin is linked to depression so I hope you can see that microbes by manipulating just these two neurotransmitters can profoundly influence our mood Behavior whether we're anxious whether relax how much we sleep how much we eat and so linking this to a disease this is interesting this is more recent study now linking gut microbes to um a disease that's called Autism Spectrum Disorder so autism so we know from looking at patients microbiotas that they they have they're Disturbed they have alterations in the makeup of microbes and also there are altered levels of what the microbes produce and there's a mouse here that can be can develop autism like syndrome in particular excessive grooming and vocalization is affected as it as it is in autistic children and what this group that worked with this mouse showed that they could restore or treat this mouse by using an probotics so live bacteria and so the live bacteria altered the gut composition of the microbes and it looked now more like normal animals and this was linked to resealing of the gut so these animals had leaky got and it was the leakiness allowing these microb derived byproducts to get into the bloodstream and into the brain but as soon as the barrier was improved the leakage stopped and it restored the normal levels that you would find in the serum and it stopped or halted some of the features of autism so this is animal experimentation but it clearly shows that there could be a role for alterations in gut microbes that are linked to neur neur degenerative diseases and autism in particular so neurotransmitters well there are also hormones producing the gut which regulate appetite and here this are they're appetites that uh are produced to say stop eating you've eaten too much no we have all we need no more to eat and then there are hormones that signals to the brain say we're hungry you need to eat and it's the balance of these two that determine our appetite regulates how much we eat when we eat not surprisingly now perhaps you think what gut bacteria can alter the balance of these hormones and these hormones are mainly produced in the gut so we know that probiotic bacteria can raise the level of this amino acid tryptophan and tryptophan is an important because it's involved in generating or producing these hormones and bacteria that live in the gut can produce mimic of some of these uh hormones in for example leptin graine py um that influence your appetite so they can influence eating and appetite control directly by mimicking the hormones normally produced in the gut indirectly they can stimulate things that will block hormone signaling to change your appetite and this is a slightly different one this is very recent showing how we with this information we can actually use it to try and redress the balance so here uh we have this chemical here which is produced as a result of a breakdown digestion of fats is called napes and as I said these are naturally produced in the small bowel as a process of digestion and lipid digestion obese individuals have very low levels compared to normal healthy individuals and so what this group said well okay what if we engineer a bacteria that lives in the gut to produce this Factor can we then reboot increase the levels back to normal and so what they showed is when they fed these bacteria producing this chemical to mice you could protect them from becoming obese so give them a high fat diet give them lots of Big Macs they stayed lean just by giving bacteria that produced this chemical and what's interesting is this persist did for a very long time even after the bacteria left the body there was still an effect so obviously this could lead to a different type of intervention using these engineered bacteria as a treatment for redressing appetite control and maybe even obesity so gut microbes you know we can engineer them and we can utilize our expertise in working with microbes for beneficial effects and you know I've try to highlight one or two things that microbes produce that influence our Behavior this is a little bit more of a list that shows things that impact on our body's function I've talked about Energy and Metabolism they can produce factors that help us blood CL blood form blood coagulation neurotransmitters I've talked about that sleep and mood they produce factors that will determine how much sleep we take whether or not sleeps beneficial and is they produce factors that cause bad breath so a variety of things that impact on health and behavior so I come to the third prediction that there is a positive selection system positive reinforcement if you like in which the type of food we eat selects for specific microbes which in turn then feed back on making us eat more of that and my example here is a seaweed diet so a stable diet selects from microbial Specialists that lead to us wanting to eat more of the these things so there's two types of seaweed diet this is one but I'm not going to talk about that one I'm going to talk about this one okay seaweed now japane in in Japan vast amounts cons of seaweed are consumed every year about more than four kilograms per person but they can process and eat seawe because they have genes present in their microbes that produce the enzymes that allow them to break down the seaweed okay the genes originate from bacteria that live on the seaweed so as they were consuming the seaweed some of those microbes stayed in the gut long enough to pass on these genes to the normal population of microbes in the gut so this microbes that contaminated seaweed actually transferred some of the beneficial end enzymes and genes they had to the normal population migr they got and so this is positive reinforcement because seaweed has lots of health benefits detoxification promotes weight loss lowers blood cholesterol so there the health reasons to eat it and the more you eat the more microbes and genes you have you acquire enable you to break it down and get maximum nutritional benefit so it's this positive reinforcement but you can only do that if you have the micro probes there and the genes present in the first place Japanese populations do because they they consume a lot of that so there's another type of food preference which is food avoidance and food allergy okay so food allergies have increased dramatically uh in recent times so more than 50% since 1997 and they've been linked to the modern lifestyle so called hygiene hypothesis overuse of antibiotics again destroying of the microbiota and so we can sort of look at this in more detail using again mice and so if we destroy the microbot mice with antibiotics we can actually give these mice analogy to peanuts just as many children have but if we reintroduce one type of bacteria into the gut we can actually cure them of their allergy and that's this bacteria clostridia so this is direct evidence linking gut microbe activity to food food avoidance okay and food allergies so not only are the microbes that will encourage us to eat more there are microbes in our gut that will stop us from eating things which causes harm smart bugs really and also sweetness and taste again if you look at Taste receptors that are present on your tongue germ free mice have different types of receptors compared to mice that have population and microbes so G free mice have a sweet tooth they prefer more sweets and have lots more sweet receptors on their tongues than mice that have populations of microbes in their guts and so nearest analogy I can come to in humans is patients that undergo gastric bypass surgery for obesity their food preferences shift enormously in fact they develop void and stretches to stop eating like some dairy products and even meat and this is accompanied by striking changes in they got micro as a result of the surgery so microbes can influence food preferences by altering our taste perception of foods so all of this together is summarized here so what I'm predicting is that food cravings are associated with vagal nerve stimulation by blocking that we can control appetite and we can reduce food cravings by altering our gut microbes we can cure uh food cravings and we can cure maybe allergies and then the diversity of our microbiota and what they produce should affect food choices and satiety okay so if we increase the diversity we have a better chance of controlling appetite and keeping us healthy and not from Gaining excessive weight so that's great so how do we actually go about changing the bugs that live in our gut so this is gut microtherapy which I'm leading to Lawn Care some you think well when's he going to talk about lawn care that's coming right so message to fix your brain you need to fix your gut and there are different strategies we can use there's the expensive one Pharmacy prescription of drugs sorry getting a bit ahead of ourselves here um antimicrobial therapy so obviously I've highlighted some of the issues with antimicrobial therapy toxicity can cause the outgrowth of pathogens like cross defil and we develop resistance our bugs develop resistance to the antibiotics and they're not cheap Vancomycin however has been used for diet induced obesity to control diet induced obesity so it's not all bad news but it's still expensive other approaches rely on biotics Pro and prebiotics and then I'm going to talk about transplants I here we go I will do probiotics here we go live microorganisms which when administered in adequate amounts confer health benefit that is the who definition of a probiotic they are found in a variety of foods these will be most familiar to you um these are generally for anybody then we have ones that are designed for children and even pets so you can give probotics to your pets evidence that they work or may work so there's evidence that they can decrease food intake they can reduce fat Mass improve insulin sensitivity stop us from becoming diabetic yogurt is the food that's most associated with reduced weight gain if you think of the things that we eat to try and reduce our weight yogurt is one of the things we generally eat and probiotic treatment in pregnancy can prevent excessive weight gain in the infant after birth so the other approach is Prebiotic and prebiotics can be considered as food to feed your Healthy microbes and if you go remember back to my gut trivia slide I said you need to consume 50 60 grams of of these things well this is what I'm talking about these are the types of food that are that will fuel provide the fuel for your Healthy bacteria and there can be in lots of things from pre-ir even toothpaste contain probiotics prebiotics food for your gut bacteria so this is what they are generally as I said they're different types of sugars breast milk is a very good source of inuline which is a very good Prebiotic and then these variety of foods here but five a day this is one of the reasons why we keep saying eat five servings of fruit and vegetables a day they are a very good source of prebiotics to keep your gut bugs healthy okay so you can take probiotics and you can feed your Healthy bugs by eating these types of foods the more radical approach is okay that's not working let's get rid of everything and replace it so fecal microbiotic transplantation so this is it in a snapshot and maybe it'll cure me of my food addictions yeah sounds gross God how the hell could this work but it does work it works incred ibly well for treating gut infection again cils come up again you know it it's a 94% cure rate which is much much higher than all the drugs and antibiotics sounds gross but it works so the question why does it work and how does it work well that's something The Institute we're very interested in knowing so it works but you might think well this is something new I've only been reading in the Daily Mail for the last year or so but in fact it goes back a long long way the Chinese were way ahead of us so and a half thousand years ago they were giving people yellow soup to drink to keep them healthy vets have been using it for a couple hundred years a pro called transformation transferring stool from one animal to another to keep it healthy first really used tested in humans in only 1958 it was given to four patients that were near death from a type of kitis it cured all four patients and then since the cific experiment you know we've treated over 500 patients no side effects whatsoever and success rate is incredibly high and it's stable so as far as 5 years out you know these people are still free of cluster defil infection so it is very good so how do we do it there are several options okay there's the crap Shu there's you know things you have as part of your healthy diet or there's the very more unpleasant way a tube and if you go on the internet you can get DIY kits that will lay to do this at home very scary stuff but you know I think we'd all prefer the cpal so what are we going to use it for so I've said you know there's some obvious diseases obesity clearly I've shown giving you some evidence that gut microbes cause obesity so if we change our gut microbes can we stop us from becoming obese or even cause weight loss Eating Disorders again I've showed you there's a link between our gut microbes and what we eat or what we can't eat so again this could be another application autoimmune diseases inflammatory bowel disease Crohn's disease UL of colitis rheuma arthritis they're all potential slightly more speculative but something we're interested at The Institute in looking at can we reverse some of the effects of Aging o not quite quite sure what that is um no I don't want BT Broadband um so yes can we reverse the effects of Aging so our gut microbes change drastically as we age and that's associ with the decline in our immune system function we become less resistant to infections I mean most some people here probably annual flu vaccines right try and boost our immunity what if we could boost your immunity by giving you a CPU would you rather have a needle or a cpal maybe maybe we can reverse other signs of aging you know maybe IFR be rich and famous because we've got the youth capsule yeah R is taking orders at the frontier and does it work well this is another example of how it works so this is fecal microb to transplant by a nasal gastro tube so this is you know the way it's been working so far taking M FAL microbes from lean donors give them to patients with metabolic syndrome these are patients that risk of developing diabetes six weeks post treatment we can clear glucose from the blood and they're now responding to insulin and this is associated with a drastic change of they got microbes increased diversity but with everything there's always a butt and this is the butt donor selection is important this is a very recent uh report that was published 32y old female with a recalcitrant C diil infection remember this is the disease we can cure with fmt she decided she wanted to take uh stool s from her daughter as the donor as you probably would her daughter was a little overweight but she later gained weight and became obese the mother 16 months post treatment have been given her daughter's um microbes got microbes became obese she gained excessive weight despite all interventions she could not keep the weight off and at 36 months she weighed 80 kilg a BMI of 34.5 what this led in this particular hospital was a complete change in the way donors are selected okay so there is the Smoking Gun here obviously the clinicians would think well it came from an obes patient we just trans the phenotype to the mother well maybe but clearly there's a link here so what we have to think about carefully now is donor selection what is a criteria we need to apply to a donor in order to be able to use their stool sample for a transplant here's the lawn care so if you think about trying to keep your gut microbes healthy you know here's our healthy flourishing lawn we can devastate it with antibiotics you know we can just let the weeds grow so if we've got antibiotics here you know we might want to give prebiotics you know Turf food or we might want to put new seed down probiotics right and then the more radical therapy a lawn transplant bacteria therapy okay so think of your gut keeping it healthy as lawn care and this is my take- home message okay if you have young children get them a pet and let them roll around in the mud let them eat mud you know maximum exposure lots of healthy microbes and with that I just thank you and I'd be happy to take any questions you might have thank you