[Music] so thank you for this introduction it is true that I'm quite out of the field you are dealing with because you are discussing the viability of parameters I didn't even know before so but I I was happy to answer a positively this invitation because it's it's always important to remember to which extent we are not not alone at all and to which extent this is deeply influencing most of the things around us you know and I say this without any potential in any profession indeed so the idea you offered me was to present you talk at my computer as the gate to the organism and to discuss this a bit related to to nutrition the gate the gate it's the entrence and the entrence is sometimes hidden if you think of it but the entrence of the organism is something which which is always microbial and that will be my first point I was looking a bit on which animal is the which for which we have the most document on what other microbes at each gate of the organism and I'm sorry the only one I found you know it by the way but and you feel it indirectly it's not very anything with linked with directly agriculture it's humans and when you look at humans being you see a lot of microbes which are at every gate to the organism the skin also all the digestive tract at lining along all these digestive tract think that for out in the intestine is 250 square meters of contact between the epithelium and you would say food but morally between the epithelium and microbes we also have it in the vagina we have it in the nostrils in the mouth everywhere where we have a contact to outside it is a contact to microbes and the result is that well the microbial cells are quite small but well as many human cells as bacteria in the gut and this idea that there is the same number of microbes and cells is it seems applying to any animals we are not an exception in this respect we tend to be very clean by the way and to be rather an exception in the other direction that we have a bit less microbes than expected if we were living in the wild and today of course the one the microbiota that will be of interest for us will be the gut microbiota which is highly diverse and my question will be a bit to address with you what exactly is microbiota is doing and you will see that it's not only present in number but it's also present in functions let's start with a bit of digestion here we discuss the gate the food is taking to enter our body I will introduce my my my ideas with an animal which is purakh cystic in terms of the role gut microbiota have in digestion because what I will show you is something that should not exist and I will come back to that and to tell you exactly why it shouldn't exist that's the Coe and many people consider the cause a typical herbivorous anymore okay whose are spending a lot of time women 18 looking like doing nothing it's 10 hours per day of just masticating like that and when you see them eating that they look herbivorous but they are not to make you convinced that this animal is not able to digest grass I just will go to the other end of the digestive tract and when I investigate the sheets of the co it's obvious that there are pieces of her and when I investigate chemically speaking with states that are able to sing either living in green or cereals in in in pink it's obvious that in this remains nothing which is the most abundant compounds of herb that is lignin and cellulose was digested so there is here the evidence in any Co sheets that cause do not digest herbs well I guess it's not a big mystery for you most of you know that this animal has a rumen that is a big outgrowth of the part of the stomach which is connected to the edge of fingers which is a big pouch filled with water something like 100 to 250 liters of water and all the herbs that are coming in and of course since this is at of course protected from oxygen there is here a huge number of bacteria and also protest cells that are developing something like millions of billions of the cells which are developing and this is producing a lot of wastes those words are mostly the volatile fatty acids like propionic acid acetic acid butyric acid which is common in the smell of the co but this is 85% of the energy the co is using the do you see me as you may know in the core is very low it's not sugar which is providing energy to the cell it's those wastes of the microbes so already we solve the problem of how this animal which is not able to digest grass is obtaining energy just wastes microbrew wastes now let's go on whose weed also bit of proteins you were discussing disallowed and we need duplicate seeds and other stuff the distal part of the rumen of this big pouch where the microbes are produced is a kind of screen a kind of sweet if you prefer we're only more microbes and small pieces of herbs are going through the pieces of herbs you saw it if the goes who this see if they will not be digested but for all the microbial cells they will be digested and there is an 15% of the enzymes in the intestine of the cause are lysozyme that is a nun time which is destroying the bacterial cell wall so it's really a digestion of microbes which is producing all but the energy the co is indeed off and we still didn't finish with this idea why the Coens masticating look the comb masticates something it's explaining from the rumen so it's already disturbed this mix of herbs and water which is in the rumen that is masticated destroyed into several species which allows better attack by the microbes because it's increasing the surface available to microbial attack but there is another thing here happening it is that the co is forcing a saliva in which it's pushing on its own wastes like the phosphorus it doesn't need anymore like the urea or the uric acid which are not expelled through urine but through the saliva and which are simply fertilizer for this rumen so if you think of it there is a reciprocal waste exchange the co is giving the the waste of its metabolism to the microbes which are reciprocally giving it largely a part of their body of course but also part or all of their wastes and if you think of it the co is not an herbivore it's either eating bacteria which are eating herbs or eating protozoans or protists that are eating bacteria that are eating herbs so it's a consumer of order two or three in the trophic chain it's not eating herb it's eating things which are eating herbs but when you look at the trophic chain in the field macroscopically this animal looks as a consumer of herb you have in this pyramid of production of biomass exactly the expected 10 time loss per trophic level which we expect if Coe is eating herps or boys or 18 cause that is that ecologically speaking this animal is an herbivorous animal but technically speaking it is not an herbivorous animal it is eating herbivores and the solution to this conundrum is very easy this is efficiency of the symbiosis first the KO doesn't have to reach its food its food is already in it so the cost of accessing the food is paid only once by the consortium of the co and the bacteria and the Protestants one but the certain see is that there is a huge efficiency due to cross exchange of wastes and this make the cause a better herbivore than horses because for horses you need fifteen to twenty percent more space and herb to feed up a horse and a cow so you realize that it's more efficient than a pure herbivore if I make color horse through herbivore because in horse there is not a woman and there is no rumination and there is no microbes behind you know this story is a story that emerged repetitively in evolution let's go now a bit under the sea this is a whale the mink well and as many ways you know it's having notice it's a misty set exactly speaking and this misty sets they are eating not big praise but they are filtering krill krill is very small shrimps so let's stop one minute with shrimps you've been eating shrimps already what are you doing with the shrimps first thing you do before it in it you peel it okay you may not peel it if it's a very small one but most of the time you have to pit so let's come back to this animal which has a lot of frames to peel and it has to peel it because otherwise the enzymes will not go into the flesh if you look at the digestive tract of this animal there is a big enormous protrusion before the storm 8 what's there bacteria Catina lytic bacteria that are destroying the skin of the krill so once again this animal would not have access to its food which you will father the digest without bacteria killing the chitin and the bacteria also flowing into the digestive tract so part of them will be also digested after what so you see this story arose many time in evolution even under the sea that you have help of bacteria to access a food you would not access otherwise well the problem is that for most animals they cannot digest their bacteria because they have bacteria but it's behind the stomach so you cannot digest them we have bacteria but they are too far away in the digestive tract to be digested well there is a first option sorry we were reaching the time of eating but I have to mention it because that evolved many times in evolution which is to eat special pieces which are made of bacteria many animals are co-produced they have two kind of sheets the sheets which is purely waste and the ones which are just a condensate of bacteria you never saw those sheets because they are immediately eaten as you can see and there are some times ten times richer in proteins than the food they ingest otherwise so the specific heats they eat is a way of read the digesting bacteria that are very in a distal part of the digestive tract but you know you don't need coprophagy to use your bacteria you your you make a good point by a lot of thing because we we do use our bacteria and we don't eat that mono gastrics as we call this animals with a very simple very primitive estimations we have they have bacteria in the intestine which are breaking down in simple molecules the complex ones that they are eating they do the same as their own enzymes in this respect this is allowing to develop bacteria to make back to your biomass and it's producing fermentative waste once again the same as previously a Gatorade propionate acetate this is also going to produce that self some of the cells of accidents they did it break they deliberate Terk on the content and all that can be used by the gutter paternal cells we have now the possibility of today exactly what I mention here by using animals especially mouse which are germ free there they are grown in a purely exilic sterile environment for generations and they have no bacteria nor on the skin nor in the ears nor in the gut and by studying this bacteria it turns out that this story is quite relevant this is five to fifty percent of the metabolic of the energy they get because they can use this in deliver this in the intestine so those molecules are contributing masters and for cause but still a bit to metabolism this is also true for you ten percent of your energy is coming from that their cells they are very important because they contain vitamins and those mouse which are axon ik they need some vitamins that the normally don't need when they are wild so it means that in the dead cells there is vitamin ik resources and finally we know so but I will not details that there is a couple of molecules from the food of the mice which are only destroyed by the microbes and if you want to feed an exotic mouse in it thirty percent more food to gain not even exactly the same weight they are very lean indeed as compared to normal mice ok so I think that the story is clear the gate for the food is by way of microbes largely but it's also a protection and speaking of that a gate is for first of all protection and we tend to think that our body has limits that we organize ourselves and at which we are selecting ourselves what's coming in or not and it's not very true let's come back to cause sorry it's my favourite example and it may not be exactly what you prefer feeling but still it's edible in Australia codes were introduced because as you know they were not present before and the growers started to introduce a legume tree called lukina which was very used in the tropics because you plant it in the field and the animals are grazing a bit of this roof which is rich in nitrogen so it was very used as a source of nitrogen throughout the tropics so it looked like a good idea in Austria in Australia 3 it turned out not to be and all the ruminants turn out to have big problem of growths or even or even survival or even reproduction when eating this in Australia weather whereas they had no problem with it worldwide it turned out that they had a problem with limousine an alkaloid which is highly toxic which is interfering with the Amin all process it's a kind of of under Korean perturbator and it was a bit bizarre because once again that was not a problem for most of the cause worldwide Jones Rehman Jones decided to study that by going to Hawaii and Indonesia and to look at animals that were eating low keine without having any problems and his idea was that probably there was a bacteria in the gut that was doing the job he took a bit of Ruben flora from those animals inoculated it to Australian Australian cows and goats suddenly they turned into being able to eat keine so if we solve the problem because the toxification of this was done by bacteria by the way now this bacteria is called from his name synergistic jonesey and it's very doubt possible to inoculate it from cultures so you see that here the toxicity of a product is simply circumvented by the bacteria and the protection is bacterial and nowadays it's very common to see in Australia those looking are planted with the cause growing perfectly around in the rumen there is a lot of protection against this which is a keratin keratin Iran carotene magnesium or calcium which is the source of food of some oxalá factors Chinese are partly oxidized into non not or less dangerous derivates by the gut microbiota and also you have a lot of energetic compounds which are simply destroyed by the good bacteria of ruminants I will now show you an animal which has a quite extreme food which is creosote this small tree here is a cross a bush it's highly toxic you may know that the extract of crows that is what we used in museums to preserve insects and it's highly carcinogenic highly toxic most of my colleagues and to optimal glab are dead on the recent years from a brain cancer which is due to crows out so it's really about story Crozier but this is the only food of this small no tama and this no Tamar you know when you give in close ot it's developing well it's the survival is a hundred percent or over the time of the experiment now let's giving antibiotics we kill is the gut microflora is gut microbiota and a normal food you see that the survival is less good but most individual are surviving now we kill by antibiotics or is microbiota and we give in creosote and then it go to death everyone is dead within 12 days so it means that this animal is not tolerating this highly toxic food it is just having the bacteria for it so you see that we are sometime not adapted to our food only our bacteria are doing the job this is a specific close-up feeder which cannot tolerate the toxins of Cruisers not more than me simply compared to me and my poor collect from the entomology connection at the Museum this animal has the good bacteria okay now I would like to make you aware that the gate has also a face inside the gate is not facing the outside only it's also facing the inside what I mean here is that those microbes at the gate their role is nutrition is not only a role outside so far they were digesting protein vitamins protecting but they were still outside in the gut they also have a role inside I will be short on that but you probably heard already of that that there are manipulating positively when we are healthy but also negatively in some case our metabolism let's take two twins one is obese and the other one is lean and we inject into exilic mice you know those mice that I show you which are fully living without microbes we inject the mice their microbiota and this results soon into adiposity and overweight in the mouse that received a gut microbiota of the obese twin whereas the mice that received bacteria from the limb twin well there are a bit bigger because the digest better but they still have a normal size and no adiposity for this animal it turns out today that one of the causing agent of obesity in humans but not only in humans is the microbiota or a specific microbiota a specific microbiota once again I mean I don't mean that is the whole exploration of obesity which has also environment who sees and genetic koozies but the fact is that part of what makes obesity is a microbiota which is one not having the same composition as the microbiota of healthy individuals and second which is less diverse that is the diversity of microbes is much reduced in these individuals this means that there is a regulation of the adipose tissues and metabolism and indeed we start to know that there is a complex interaction between gut microbiota and the brain it's better known form often for humans but we know that the gut microbiota of obese individuals is producing a lot more of acetate and that this high level of acetate is on the mouse brain producing several effects which are producing as a result obesity first by way of the vagus nerve it's an ensign the secretion of insulin which is an ensign the ability of the cells to take up the metabolize from the blood and make it into reserves second by way of the vagus nerve again there is action on the stomach which goes which enhance the production of an almond the ghrelin which back to the brain is anything the food intake by simply lowering the society you eat but you still feel hungry because you don't feel anymore the signals that you've been eating by the way one of the most efficient signal that you've been eating which is making this lasting feeling of not being hungry anymore but the very first one is mastication the second one is making the stomach full this is lowering our greediness for food but then after few hours we stop masticating we have nothing more in the stomach is the beauty right of the gut microbiota which is low boring of feeling our envy of eating so normally the beach right the BT rate is topic that but with the excess acetate produced by the gut microbiota of obese people you go into dysregulation eating more and making more reserves from what you get from your food so you see they are at the door but they also are busy indirectly on what is happening inside and you know this story of the fact that some microbiota are producing obesity remembers me of another story you may know that it was for long a mystery to understand why giving low level of antibiotics to animals was making them becoming healthier because the level of antibiotics that were applied we are much lower than for having a true antibiotic effect on pathogens and so on so it was not a kind of preventive effect it was something else not so well understood and we know now that simply the perturbation induced on the microbiota by those low level of antibiotics was simply promoting an obesogenic microbiota and when you look at the composition of the gut microbiota of animal which received as the level of antibiotic there is a sceptile change in a microbiota which is different from non treated animals and much less diverse exactly the trend you have for aboriginals or obesogenic microbiota but there is more the not only influence our metabolism and reserve making and functioning of the physiology but they also influence the behavior of the animals I will just show you a couple of data on stress and interaction between animals this is the story of mice that were stressed or grown in non stressing conditions when you take those animals the level of cortical stearin an almond related to stress is much higher when you stress them that's expected after stress you are secreting the hormones which are making all the reactions could be more or less we stress at a huge energy cost of course now let's feed those animals by lactobacillus lactobacillus rhamnosus by the way Destructo bacillus conduces has the same impact on humans so normally I should a slides on humans but here for you I was digging out the slides on mice and you see that when they are treated there is a difference but there is a significant lower accumulation of cortical stearin as compared to the non lactobacillus rhamnosus mice so you see a stress but it's pressing much less cost cost iran now let's go into something which is more behavioural which is more integrating the status of the animal there was this note that when you feed a mother during the pregnancy with the rich tight so during the pregnancy and after the the birth of the of the young mice if you give a rich tight rich in lipids and rich in proteins versus diet med of more fibers you see that the offspring the offspring it's a funny transgenerational effect the offspring are is much less interacting when the mother received a rich tight so what your mother is eating which makes you more or less prone to communicate with other mice it's estimated by time of interaction with other individuals in the same cage it turned out soon that one of the difference but this is purely correlative one of the difference between those offspring and those ones was that when there was a rich diet the gut bacteria were seeing currently depleted or even there was even no lactobacillus reuteri but this is pure correlation of course because of this correlation the scientists decided to take those offspring with the rich from a mother with a rich diet and reintroduce focus probiotic le the rent election of the October see rotary and what did they found body defined they reverted the phenotype just by adding this bacteria and it's funny that you can manipulate the awareness or the contact to others by bacteria and it opens a lot on not only the way of hunting cattle or hunting animals were also the way of maybe tomorrow of hunting humans health and relationships I lead you on that and I go to my last point we are in an area where you know biodiversity is decreasing everywhere by the way you already heard I mention it that in obese people there is a kind of reduction of biodiversity in terms of gut microbiota good microbiota are also in this area of biodiversity extinction the gate of organisms are in the modern society much less microbial than they were in the wild let's start with human if you want and we'll come back to animals later here is a saturation curve obtained by sequencing effort increasing sequencing effort of faeces of group of people that are either from non contacted tribes by non contacted you should understand that they had no contact with Occidental civilizations of people so only the dank were harvested not more those are amazing young groups of people there's so many is in young groups of people have more or less contact that not a lot but they have some contacts with European lenders are in in yellow US citizens you see that US citizens of only 2/3 of the diversity of Yanomami and that gua Hebo and Malawi which are partially contacted have intermediate richness so you see this decrease of richness which is associated with the gradient from ancestral type of life to Occidental type of life that's well characterized the other thing is that when you look at the composition in a PCO a analysis of the composition of the microbiota you see that the us are very different in terms of composition from the mojave choirboy and Malawi story and also from the Yanomami there is one Yanomami here which is a bit funny because they have a bit of contact with some Malawi but we don't know exactly what he is doing with when i whistle well is our point anyway you see that you know me out there US citizens out there and the partially contacted populations are in between it's a funny trend but it's not so funny when you think of it because there is another story which is connected to that one these are the story starts like a good news over the 50 60 70 last years we were killing most of the bacterial virus we didn't want and we end up with reducing a lot of loads at least in Occidental civilizations we were able to reduce the load of many illness but at the same time it happened that many illness that we don't want we're growing prodigiously growing for example metabolic diseases like obesity or type 1 or type 2 diabetic meanness of the immune system like multiple sclerosis crohn's disease where the immune system is simply killing the body or overreacting immune system like asthma or if you have children you may know that dermatitis atopic dermatitis which is a skin rough very painful which is now a problem for one third of the children of under five years so human system metabolism is not working well sometimes it's also the brain autism was multiplied by three time in ten years in Occidental civilizations now one child out of 158 births is more or less at values level having autistic syndromes can you guess that autism was unnoticed at the beginning of the 20th century asthma had no name until 1906 does unless indeed you can't find them in Amazonia or hardly you look awfully will find them but at a very low level what's up you look at the gut microbiota but also even the lung microbiota or the skin microbiota of people that are aged the ill or healthy for all the illness I mentioned you can see that they don't have exactly the same composition and that on average there is much less diversity in people which have the symptoms is it a cause or a consequence first I showed it to you on obesity when you give those microbiota from in people to mice you end up with mice having subtly but surely symptoms that are reminiscent of the symptoms of the illness like for example you get autistic microbiota to mice they interact less with the animals from the same cage second when you transfer microbiota from LC individual to individual you read use for some time the level of the symptoms so for some time only and not free which means that there are other cause also acting but that microbiota is part of the causes so coming there we experience in ourselves a reduction of biodiversity which is reducing the efficiency of the microbiota to play its normal role at the gate of algorithms and which is enhancing the development of some illness and then comes the question what about the animals we capture the nature and what about the animals we domesticated story is not fun because they have the same problem if you go to captivity we all undergo some kind of captivity you know so if you go to captivity for example and compare animal in the wild and in captivity you see that the animal in the wild so it's a PC or a analysis of primate gut microbiota compared to humans you see that in the wild the composition is much more disturbed from human that when those primates are grown in captivity in captivity this is the those great point here this brown point sorry you see that the gut microbiota tends to resemble that of humans probably in fact because the food resembles that of human but the fact is that when you enter in look at that more carefully you see that there is more profit Ella and bacteria details that that's the facts for all those animals and this is driving the similarity to humans and but more interestingly if you look at the diversity you can see that in the wild it's higher than for semi captive individual lucha contacted by humans but still foraging around and it's even less when they are captive so they experience a change in quality but also a reduction in diversity of the microbiota another funny story was investigating animals in captivity versus from the Kalahari Reserve and for many individuals that were investigated there is a significant change in the number of bacterial species present in the gut most of the time it's a reduction which is significant for all those animals like dogs for example but which is interesting is that there is an only one exception which has rhinos rhinos they have more diversity in captivity but with exception of of rhinos on average there is a reduction of diversity okay so now you will tell me that it's a funny story but we don't mind the question is what is the health of these animals well just one thing before we we go back to the end of that you see that there is more film Acutes and more bacteria detests in most samples and this is what just what I told you about Privitera and bacteria tests before it's real trend when you approach humans you tend to have a lot of that and it's not a good news because those groups are the one which are obvious unique well-kept even domesticated animals tend to be more of a noble Obi's than in the wild but let's come to this biodiversity extension is not only an extinction of species it's an extinction of functions there are things that were made before that are not made after the extinction and this is reflected in the health of the animals let's go now to fully domesticated in the animals lab mice we have those from the lab they are not exact okay these are the normal ones from the lab in the dirty cage and when you compare them to the mice captured in different location in the wild versus different labs in the US you can see that the diversity of microbial diversity is not the same and there is a group which are Proteobacteria which is quite abundant in the gut in the wild which is nearly absent it's nearly but honestly on the diagram is nearly fully absent from the lab while theame kids once again are invading those gut microbiota so you'll see that domesticated individuals they tend to have a different microbiota now what is the consequence in the same paper which is an outstanding one in my view they were investigating three times or three types of mice those from the lab simply and germ-free mice with one which they have we're transferring either the microbiota of lab mice or the microbiota of wild mice so I create a lab micro biota Battiste microbiota from a mice from the lab or Wildman profit is a micrometer from nice from the white and then the work challenging does animals with which you read the paper tons of things ok I will only take one thing influenza A virus which is killing mice and so you see that the survival is rather good for those who receive the wild microbiota and rather proof orders that are either grown in the lab or received being Jam free the lab bank Rob Utah you go to 20 percent survival upon 10 days but in the wild it's not so much of a problem to get this and if you look at the titer of this virus in the lungs which making the most problematic issues you can see that the title is significantly higher for lab and jam-free lab mice than for germ free mice that received the world microbiota so really our domesticated animals they lost the diversity and they have the same problem that we have with the modern microbiota in our own body there is a biodiversity instinct ssin leading to less function that are vital for a healthy response to many things so we we are at the end of the story but it's only the beginning of the true story that you will make the microbes out there and they are active and the less microbe we have the less de sac tivities out there it's not the new story I would like each of us to feel deeply guilty at this point a bestseller from the 69 wrote written by Rose Barry very Road by normal people but maybe not by scientists or maybe not by technicians was life on man at the time you know it was life on moon life on Mars but simply Rosemarie was working on the bacteria of the body and he was making this book to report that he says that in the book but Jeffery animal is by now by a not a miserable creature he was already claiming all I told you in the desert because at the time no one was listening to that it means that somewhere someone is saying something that we don't hear and that is a tool for the future but clearly now we have to imagine that when we feed animals that's my contribution to your discussion and you may find it a bit stupid but you don't feed an animal you feed back to your rabbit yeast ecosystem which is lowing the animal to develop if you think of that I think that there is a room for improvement in the way we handle domestic animals by considering that there are microbial ecosystems it's only a way of seeing them but clearly there is a lot of heuristics there is a lot of new procedure to Ebay gene when looking at them from this angle of view this point of view that we never before we're considering and it means that in terms of the door you know they're often we like cleaning in front of our doors but you know a dirty door may be better than a clean door in this respect this idea of clean dirtiness is not a paradox it's not a paradox it means simply that our technical and cultural standards are now too few contaminated as compared to the biological standards of animals on humans and this is a big challenge for the future to reintroduce the dirtiness that is a contamination that will not reintroduce the disease we try to escape but which which will reintroduce all the diversity we need to restore the functions we lost in domesticated animals or westernized Occidental people well you don't see them but they are there by millions on those pictures you see many animals but I see microbial communities and billions of billions of microbes as you said all those animals are never alone this is the French word for it Jame Searle they are never alone so of course it could be the title of a book it's even a book in Polish as you said but once again clean means dirty and this is what we have to imagine for the future and I don't know if it's an easy step to go forward in this direction I'm sure we need a generation we need a generation not to laugh when you see clean dirtiness but you have to go forward in this direction there is kind of emergency this is one of the point where biodiversity decrease is crucially problematic for the future thank you for your attention [Applause]