Gut bacteria and mind control: to fix your brain, fix your gut!

right well thank you anyway reg for the introduction so as Ray 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 and eat are our gut microbes and they're a direct link 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 see 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 I've got microbes was by what we could culture on a petri dish and since we now know that about 80 percent 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 microbes 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 micros that we cannot culture and so this has led to massive interest in gut microbes and some of these are very recent so the Daily Mail

thinks that 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 nutrients good beneficial nutrients in them but rare the message here is that what we eat influences 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 I would say you need to ask so the obvious one is well so what do these differences they're detected do they really matter are the changes the 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've 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 are for our health and well-being and then how we actually might manipulate they've got microbes to improve or restore our health so that's what I call Lawn Care

right start with so the gut mouth to the anus it's a long tube here's a picture taken with an endoscope and you can see it's not a smooth tube it's got these ridges to it the muscles 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 Lumen to capture nutrients and absorb them so the tube is quite long it's about nine meters from mouth to anus and somebody has taken the trouble of trying to calculate

what the surface area of all these billi 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 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 five to fifteen percent of our daily energy requirements in some animals it's up to 30 percent 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 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 a 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 and normally that will be jam-packed with bacteria most of Derma 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 we use to describe these microbes the microbiota which is to describe all the microorganisms that live in the gut and there's

the microbiome and that's all the microbes plus all their genes combined so microbiota microbiome two as you may have come across in a lot of these articles but individually bacteria are incredibly small so this is the head of a pen 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 trillion 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 will 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 ninja just to give you an idea of the scope and scale of the numbers here of bugs and 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 percent 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 little of it is our own okay now this is the audience participation bit some trivia how much do you think

all of microbes in our body weigh don't be shy PhD students at the back come on how much what stop conferring so anybody else kilogram closer two kilograms two to three kilograms a lot right a couple of bags sugar and if you put it in a volume size about one and a half liters and there's about a thousand different species thousand different types packed in there and this is what they need to keep them healthy about 50 to 65 grams 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 expelled gas how much do you think we expel every day how many liters how many five no it'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 sixty percent 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 and 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 compromised they're deficient so they have nutritional deficiencies they don't grow but interested 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 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 the pathogen to these animals they 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 that there are really poor animals very sick so the microbiota and the micros 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 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 dizygotics 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 microbiota 2 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 are not unsurprisingly these are concerned because they perform important functions such as ones here degradation of carbohydrates that 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 a particular 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 it's 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

by 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 theater 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 later on set of various diseases and disorders back to whether or not you are 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 it's a normal birth or is it does it require intensive care the age at Birth is also important is it a full-term birth or preterm birth and hygiene obviously where

you're born the home versus the hospital a very different population 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 grow older we get exposed to micro some other sources and by different routes 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 we have pets if we live on a farm we're getting exposed to 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 the 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 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 populate us now here's a fact most of you probably didn't know okay interesting one to experiment on so intimacy and you know it's across the animal kingdom different types of interest me 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 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's 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 a and also 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 antibiotic two antibiotics to treat

Clostridium difficile 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 Vancomycin or metronidazole 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 clostridium 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 long-lived effect on our microbiota so antibiotics could be described as a man-made catastrophe however most of the antibiotics that are used are used in agriculture and in farm animals in particular to check infection and 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 U.S by two

years of age most children had at least three courses of antibiotics and there's phenomenal number of doses of antibiotics given out in the U.S and what this does is it drives bacteria to become resistant and this is serious okay so this particular organism here MRSA 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 the number of people dying from AIDS I don't know if you've just seen on the news today but there's a

UK Government Review group is recommended the pharmaceutical industry invest two billion dollars 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 tail 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 the 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 also how the body reacts to the drugs and here are some examples so the bad ones are these drugs here which are painkillers anti-cancer drugs drugs used to control high blood pressure in certain individuals that have certain population microbes administering of these drugs will lead to increased toxicity and with some antibiotics as well as 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 so the drugs will be given to you because you have been determined 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 thing it's not a map of the galaxies it's actually the results of screening them the microbiomes in a lot of different animals and this is sort of a zoo collection each dot represents similar microbiota's in populations of animals and the lines of Separation here indicate how similar or related they are to other microbios in other animals so we've got these sequences we know

all the microbes 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 leaf-eating monkey 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 Burkina 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 diets changed and it's caused this profound shift in the micro so the diet really is a driving force in making up the microbes that you have in your gut and 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 fasting 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'll decline again so fasting reduces the overall diversity and then feasting expands the diversity in response to diet it's a 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 noradrenaline norepinephrine and Ephraim which are all part of adrenaline are produced in response to stress and that can

have a direct effect on the bacteria that live in our gut and it can cause the outgrowth for particular types of bacteria so here for example ten thousand full increasing growth in response to adrenalines 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 the bacteria little circular shapes but then under food deprivation which

is the 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 there's one from Morrisons and this is actimel they contain bacteria that produce a neurotransmittical Gaba and Gaba is normally produced in the body and 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 over stimulate these receptors to make you even more relaxed and in fact even knock you out because anesthetics can work by mimicking the Gaba that is produced by these bacteria so benzodiazepines 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 out 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

straight state state and so one of the other things I wanted to highlight here was this obesity lots of evidence in the literature now and in the newspapers that uh changed in our gut microbes to make can make us obese so I've got microbes in 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 or 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 low fat High carbohydrate I mean low fat high fiber diet the ones that got the 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 hype that's a bit more close to fact so of course it's mice it's not humans but this is the best evidence we have to date that shows the

direct causal link between our gut microbes influencing whether or not we stay lean or whether become obese and then this was in the Sunday Times this week this is from a study carried out by Tim Spector at King's 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 Coke and then he was taking still samples before and after the 10-day diet and what happened what he showed was that first of all there's a reduction in nutrients because

he's now eating this very processed refined Foods there was a loss in number of he's got microbes but he gained two kilos in weight in just 10 days so the interpretation of this is that highly processed foods present in Big Macs containing ingredients 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 with it so I'm not don't 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 diseases in particularly inflammatory bowel disease and Crohn's disease so the loss of diversity in the types of microbes having a gut is not good it can have quite profound health effects and so it's not just gut 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 fat and rheumatoid arthritis there's lots and this is a not a complete list by any means so obviously well is there one microbial one population of microbes that can cause these diseases so it's like looking for Waldo found him yeah there he is the only problem is there are lots of Waldo's 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 could be Rowdy or they can be miserable and anti-social so it's the population when they come together that they causes or is probably responsible for the effects in 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 us and I really like that piece of cake okay and it's maybe that gut feeling you 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 behaviors that's what we're talking about brain development Behavior so this is next this is a summary of an experiment carried out a few years ago looking at our germ-free mice again these are sterile mice and mice that have population that 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 light 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 curious I'm 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 gut microbes you know it's the Great Escape you're looking for ways out more striking experiments this one's shown here so we've got two strains of mice what we'll call timid and adventurous so they've got microbes 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 germ free mice so they're an empty vessel that you can put the microbes into and they became now adventurous 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 you're always 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'd become a bit more outgoing a bit more social maybe no 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 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 they hear 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 pain killing drugs like morphine for example you know there's a risk of constipation and 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 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 enteric 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 nerve fibers actually penetrate and intermix between all our gut tissue and they actually look like they're actually protruding into the Lumen to be able to sense perhaps the

presence of factors that they can respond to that are in the gut Lumen that could be made by gut microbes and the vagus nerve is ultimately this the root by which all this signaling in the gut leads into the brain so all these signals here that these the enteric nervous system responds to are fed into the brain via the vagus nerve and so we know that if the vagus nerve is blocked or damaged through injury profound effects on appetite and eating in fact it causes drastic weight loss so it's clearly a regulator of body weight

and vagus nerve stimulation by hormones and neurotransmitters in the gut and drive excessive eating Behavior so overstimulation is not necessarily a good thing and not surprisingly gut microbes can actually regulate how much of these neurotransmitters 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 cyst 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 the 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 so you may know that l-dopamine is used to treat Parkinson's disease serotonin is even more striking because virtually all the serotonin bodies 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 we're relaxed 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 had 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 particular

excessive grooming and vocalization is affected as it is in autistic children and what this group that works with this mouse showed that they could restore or treat this mouse by using ant probiotics so live bacteria and so the light 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 a leaky gut and it was the leakiness allowing but these microbe 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 it could be a role for alterations in gut microbes that are linked to neurodegenerative diseases and autism in particular so neurotransmitters well there are also hormones produced in the gut which regulate appetite and here there's a they're appetites that are produced to say stop eating you've eaten too much now we have all we need no more tree and then

there are hormones that signal to the brain State we're hungry you need to eat and it's the balance of these two that determine our appetite regulates how much we eat and when we eat not surprisingly now perhaps you think 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 isn't important because it's involved in generating or producing these hormones and bacteria that live in the gut can produce mimics of some of

these hormones in for example leptin grayling pyy 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 produces the result of a breakdown digestion of fats it's called napes and as I said these

are naturally produced in a 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 persisted for a very long time even after the bacteria left the body they were 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 I've got 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 tried 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 bodies function and I've talked about energy metabolism there can produce factors that help us blood clot Blood for Blood coagulation new adjustments I've talked about that sleep and mood they produce factors that will determine how much sleep we take whether or not sleeps beneficial an issues they produce the factors that cause bad breath so a variety of things that impact on our 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 feedback on making us eat more of that and my example here is a seaweed diet so a stable diet selects a microbial Specialists that lead to us wanting to eat more of 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 Japanese in in Japan vast amounts of seaweed are consumed every year about more than four kilograms per person but they

can process and eat seaweed 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 enzymes and genes they had to the normal population migrants in their gut and so this is positive reinforcement because seaweed

has lots of health benefits detoxification promotes weight loss lowers blood cholesterol so the health reasons to eat it and the more you eat the more microbes and genes you have you acquire enabling 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 microbes there and the genes present in the first place Japanese population do because they consume a lot of that so there's another type of food preface 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 microbiota in mice with antibiotics we can actually give these mice analogy to peanuts 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 bacterial clostridia so this is direct evidence linking gut microbe activity

to 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 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 microbes so during free mice have a sweet tooth they prefer more sweets and have lots more sweet receptors on their tongues than mice that her population of microbes in their

gut and so the nearest analogy I'd come to in humans is patients that undergo gastric bypass surgery for obesity their food preferences shift enormously in fact they develop avoidant stretches to stop eating like some dairy products and even meat and this is accompanied by striking changes and they've got microbes 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 food cravings and we can cure maybe allergies and then the diversity of our gut microbiota and what they produce should affect food choices in 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 guts so this is gut microtherapy which I'm leading to Lawn Care somebody thinking well when's it 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 could cause the outgrowth of pathogens like prostodium difficile and we develop resistance our bugs would 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 administer inadequate amounts confer a 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 these are generally for anybody then we have ones that are designed for children and even pets so you can give probiotic 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 prebiotics 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 these things well this is what I'm talking about these are the types of food that I that will fuel provide the fuel for your Healthy bacteria and that can be in lots of things from pre-bird 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 inealing 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're 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 microbiota transplantation so this is it in a snapshot and maybe I'll cure me on my food addictions yeah sounds gross God how the hell could this work but it does

work it works incredibly well for treating gut infection again C difficiles come up again you know 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 it 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 two 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 the process called transformation transferring stool from one animal to another to keep it healthy first really use tested in humans and not in 1958 it was given to four patients that were near death from a type of colitis it cured all four patients and then since the C difficile 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 five years out you know these people are still free of colostrum difficile infection so it is very good so how do we do it there are several options okay there's the crabsule there's you know things you can have as part of your healthy diet before there's the very more unpleasant way a tube and if you go on the internet you can get DIY kits that will allow you to do this at home very scary stuff but you know I think we'd all prefer the crap show

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 I've got microbes can we Stoppers from becoming obese or even cause weight loss Eating Disorders again I've showed you there's a link between I've got 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 ulcerative colitis rheumatoid arthritis they're all potential slightly more speculative but something we're interested in

the institute in looking at can we reverse some of the effects of Aging not 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 associated with 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 Geri minutes by giving you a cropsial would you rather have a needle or a corruption maybe

maybe we can reverse other signs of aging you know maybe if I'll be rich and famous because we've got the youth capsule yeah Reggie's taking orders at the front here and does it work well this is another example of how it works so this is fecal microbiota transplant by a nasal gastro tube so this is you know the way it's been working so far taking my fecal microbes from lean donors given to patients with metabolic syndrome these are patients at 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've 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 reason a report that was published 32 year old female with a recalcitrency difficile infection remember this is the disease we can cure with fmt she decided she wanted to take a stool cell from her daughter as the donor as you probably would a daughter was a little overweight but she later gained weight and became obese the mother 16 months

post-treatment had 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 kilograms 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 obese patient we just transferred 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 the 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

lone transplant bacteria therapy okay so think of your gut keeping your health is 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 thank you and I'd be happy to take any questions you might have thank you