ESPN 2019
The rise of the holobiontic approach of organisms
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Gut health
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[Music] thank you honey thank you dannion for this introduction I'm not at all a poultry person I think you will be convinced of that in a few slides but I'm very pleased ladies and gentlemen this morning to introduce you an an emerging way of seeing life which is now running into many physiology ecology of zoology labs which is the view of Hawker isms as horribleness well how many chickens something like for how many organisms if you think for listen carefully to what follows because it's not for at all well the idea is that we turn now to see animals as hollow beyond and I would like to introduce that by the functions to microbes which are embedded in the animals are doing the first thing they are performing is a help to digestion here we have to go sorry with Mice and mice our wonderful model because we we have sorry we have a wonderful tool with the exilic or also called germ-free mice with which are grown in sterile environment and have absolutely no microbes nor on the skin nor in their ears nor in the gut there are acts in Akita jam-free they are sterile and what we know from them is that they are not performing so well many functions like digestion the microbiota of the of the gut the microbiota of the Gert ok I still have it they help to break down complex molecules into simple molecules which are incorporated in the cells of the microbes in part those microbes are liberating fermentative products such as volatile fatty acids and of course some of the cells are going to DES and explode or decay in the digestive tract all that is their life but it's also good news for the host because the host gut epithelium is harvesting some of the simple molecules some of the content of the dead cells and also some of the volatiles those volatile fatty acids for example are responsible for 5 to 15% of the energetic balance of the organism this is developed but acetate can be converted to glucose butyrate is used in the intestine so as a result those fatty acids are a part of the metabolism of the host that cells are very important in providing vitamins germ-free mice need vitamins that you never give to wild mice or normal lab mice so that means that does cut bacterial protein vitamins and finally part of the simple molecules issuing from the microbial digestion are used by the gut epithelial cells so that the germ-free mice the exilic mice they need 30% more food than the normal lab mice because they digest not so well well so that's an extreme case where there is no microbes but I will also to show you to which extent to micro are shaping the way the gut is handling molecules such as toxins or Pro toxins the modified and the toxicity or the non toxicity or the efficiency of any medicine you can put in the digestive gut depends on how the gut bacteria are handling it or not hunting it let's make an example you may know that mel amines are molecules that are added to some food as to increase the apparent content in nitrogen the content in nitrogen and the apparent content in proteins there was a big scandal on milk in human nutrition the problem with melamine is that some individual but curiously not all are converting melamine into Shan uric acid and this generic acid is leading to crystallization in the kidneys of big crystals of melamine generic acid and uric acid which are simply destroying the kidneys and it turns out that the trunk the dr. synthetics the synthesis of generic acid which is the driving point for formation of the schedule's is due to bacteria from the gut so the fact you can be intoxicated either as a human or as a rat on the screen by melamine is not due to melamine itself let's look at the content of melamine of the kidneys and the content of shanwick acid of the kidneys of animal fed with melamine but without any Klebsiella theory Jinnah and there is a small content let's now put epsilon in the food and you end up reserve heavy deposit killing the kidneys so the toxicity is due to the interaction of the product and the gut microbiota there is a huge story with the gut in terms of digestion but there's also a huge story in terms of protection because germ-free mice are by large very harmless animals in front of microbes I would like now to show you a bit of the skin because you know there is a microbiota on the skin and it's very overlocked we speak a lot of gut microbiota but there's also one on the skin you know the one we are washing every day and what happens when it's not there not good news let's try to put less money on ashore a big diseases of the skin Kathy I can go inside the body on mice let me first tell you that my stay usually not suffer less manatees and you can see that normal mice when you put the illness you get into a huge reaction which is expelling in control gentle mice to illness germ-free mice which have a much thinner skin they perform very badly in many respects they don't make any reaction and they catch this Easy's which is digging holes into the skin up to vital organs and when you look at the size of the lesion clearly they to jump from eyes under echt the very nice thing is that you can make some experiments to show that by restoring a skin microbiota you restore the functions let's few days before you put the leash man Yama your parasite let's put back in the cage on the skin of those animals Staphylococcus epidermidis something very simple the animal you see here for example has like 100 millions of them on the skin so it's a very painting company component of the of the cut of the skin microbiota and then few days after that we put the leash man uses agent the Leishmania measure on the skin and we go to a bigger reaction when we look at the activation of the specific white blood cells responsible for expelling Leishmania Mayo you see that there is a huge induction in normal mice much lower in a clinic mice and normal induction in exilic mice that received this usual skin microbiota contact or bacteria and you know you will tell me it's a bit extreme because here it's without microbes versus with microbes but there is a big problem running around that love mice as compared to wild mice have much different and indeed much reduced biodiversity of microbes in the skin microbiota look for example Proteobacteria are very common in white mice and nearly absent there is a small green line but like nothing in lab mice is they have a very different microbial diversity and it's rather a bad news for them let's make let's compare three type of mice a lab mice normal another one which first jam-free and has been inoculated with the microbiota from lab mice and the third one which was jam free but has been inoculated with microbiota from wild mice so let's now challenge them with a killing agent for mice which is influenza a virus we can see that the survival is good with a wild microbiota but very low if you are a lab mice or a germ-free mice infected with live microbiota and the level of infection is high when you are with a lab microbiota or when you are a lab mice versus rather low or lower and indeed you don't go to death or rarely go to death when you are infected with the wild microbiota it means that and it's a general rule that I'm sure applied to your animals we have domesticated animal and reduce the biodiversity of microbiota and the result is that now they are facing problems which don't face with a normal microbiota for the poultry it's your role to check that let's go now to the final point that microbes are also agent for development and let's investigate the behavior of mice in this design a design in which you have an elevated cross with two wings surrounded by big walls and two wings open and we put in that a normal mice the mice is exploring the protected area looking outside checking that it's not a place for any Mouse the open side and goes on with the protected size normal Mouse uh normal mice are photo phobic and stay hidden please remember you the Tom and Jerry films from your use the mouse is always hidden now let's go to an exam ik mices there as you can see it's exploring zone looking outside going out only me which is very dangerous but once you make such an experiment on yourself don't do that quite dangerous and it can be eaten by any cat or killed by a meal in human beings around we go hidden no it will not you could consider this is simply a timid and a risky mice but there are two sisters born sterile of which the first one was taken out of the sterile environment after birth so they are genetically very close and when you repeat this on many pairs of sisters you end up with the fact that exilic mice have significant different behavior being more risky than the normal mice with microbes and this wonderful work by Diaz hates which I recommend to you goes father not only they are able to show that in the central nervous system the synaptic turnover that is the speed at which the neurotransmitters are recycled is much low is much faster in axonal mice but also by in situ hybridization they are able to show that all the genes expressed in the brain are expressed in a different way in a clinic versus white mice such as this marker of and City much less expressed which correlates at least but medic partly explains the behavior of this anxious less exilic mice also this marker of synaptic plasticity which is less expressed and that correlates and maybe explains the fact that ethnic marks are dummies they learn much less fast than normal mice so the development of the brain is not the same and its development because take a mice out of the exilic environment as long as the development of the nervous system is not over and you will turn it into a normal wild-type mice take her out or take it out of the sterile environment of after development of the nervous system nothing will happen it's really that they are said that these micro guitar sending messages to develop the nervous system and from there the behavior last bit wrong behavior about interactions let's look at the way in a cage some offsprings of mice are interacting when the mother received a rich diet or a poor diet you see that when the mother is a poor diet there is much more interaction between the offsprings and when the diet it reached is rich it turned out that it was correlating with the absence of lacteal lactobacillus reuteri in rich diet animals so the authors of this of a nice paper tried to see whether it was causal or not and what they did is simply they got some offsprings from a mother receiving a rich diet gave to the soft springs lactobacillus reuteri and the rest thought the normal behavior in terms of interaction so even after the development of the nervous system this may also influence the behavior of animals including mice and I'm afraid probably months if not paltry so when you see that you have the feeling that an animal is not animal without bacteria or yeast or anything belonging to its microbiota that raised the idea of the hollow biome that is to consider the host together with its associated symbiotic organisms a term coined in 2007 or before in specialized Congress the idea that before we are seeing the animal as the one entity an autonomous entity closed at its border a kind of piece of the system an elementary piece organizing its autonomy we know now that there are many microbes that they are contributing to this autonomy and achievement of the physiological functions and now we want to consider the whole of that so there were millions if not billions of people there and for hollow bones but I would like to go father is it really a good idea to consider hollow bones many of us are going one step father with that and I would like now to show you a bit of plan stories you told that I have a bit of problem with plant science it's my thing so let's look at plants plants have roots okay but what we know and this is the model my teams are working on is that those roots are infected with fungi and this dual interaction with fungi fungi being in the soil as well but also inside the root is allowing a reciprocal nutrition of the partners this is the root part of the whole biomes in plant the fungi are providing mineral nutrient to the plants while the plant is feeding the fungus with derivates from its photosynthesis that's part of the plant hora biotic story but the fact is that the fungus is in the soil exploring the soil and it may connect one root and another root from a different plant sometime from different species so in a way this fungi are not only part of the whole point of each plant but also linking together those plants and if you think of it that's making a network plants linked by fungi of fungi linked by plants to colonize each on a different route and I make it very short and fast ok I don't want to bother you with plant but what my teams are working on on phone is that some plants have lost clear of Island photosynthesis because they simply use this network the shirt fungi with surrounding trees to get their carbon but there is more we found that some plants which are green in the forest also are networking with the trees and re-save in addition to their photosynthesis as an adaptation to dark condition in the forest they receive also carbon you want an evidence for that I could pilot tons of papers and isotopes labeling blah blah blah but I will just show you an evidence some individuals mutant that lead profile to survive very well this one was surviving this individual who has a rhizome that was surviving 15 years 15 years without photosynthesis just because there is sugar flowing through this network so for plant it's clear what we face is that some of the microbes are making a network a network where they can exchange nutrients a network where some other teams have been showing exchange of signal when one plant is bitten by aphids or parasites plants linked by the mycorrhizal network are enhancing defense against a predator or parasite they never saw but they have a signal that it's here meaning that there is also information running no one knows what is this information but the facts are there and of course finally and simply if you in the front and me are sharing of fungus and if you are giving more carbon to this fungus than I do even without direct interaction between you and me someone is paying more for the common good than the other in other word even without exchange of signal or nutrients this network may allow indirect interactions between plants because they may not paid the same price for what they get from their partners because some of them may be more or maple-glazed by the way so to finish with that where is the hora by aunt now I have a plant okay sorry it's complex but they are fragile of course the samsaya are connected to other plants which are helping this fungi and maybe giving to the focused central plant but the sponsors who have Mike Russell Associates which are connected to plants where is the hora by aunt I think that when I make the hora by on here I make first order approximation of a much more complex system with many more others and there are many networks if you think of that plants are sharing pollinators they are sharing clones of Agra sauce they are sharing clones of root bacteria they are in the middle each plant is the middle of a complex network ah nothing to do with animals all removed as a not animals these are all over okay so well let's put the device microbe on that okay now in the microbes these two animals are sharing some may be from the same clone we know that bacteria can influence the behavior and what if the sharing of common microbes was affecting the behavior of these two animals one toward the other because there is a link now which link between the bacteria of the clone but it may affect the hosts what about that is it science fiction the fact is that it looks so bizarre that it was hardly investigated but there is one paper which is a lot of fun and that I would like to share Philips finally finally with you to show you that there may be some invisible links due to the sharing of bacteria between animals let's go for last paper then this is a nicer Sharon and coworkers paper also in class where a Drosophila melanogaster have been grown either the colony was divided and grown either on starch or on a different medium which is the original see my might medium which is usually used for my father sorry for for Drosophila so we are with insects now it turns out that starch changed the gut microbiota it's not unexpected because we know that the gut microbiota depends among other parameters of what we put in our gut and starch grown through Sophia have more lactobacillus plantarum let's now take starch or see my drosophila and try to make a general matting so I invite you to a sex party by insects now all in the pot and they are doing what they want with who they want but with who exactly we can label them and we can see who is doing what with whom so it's a very exciting issue I do you prefer starchy or see my ones and here is the result Omega moose mating are quite frequent that is Drosophila male and female only industry from same food it's much more frequent than hetero gammak Matti that is proof having a partner from a different food there is a bias in partners choice whereas it's the same let's say family or or descendants now let's put antibiotic on all those guys ok before sex so first antibiotics then sex no more by us huh isn't the lactobacillus plantarum playing tricks let's after antibiotics give back lactobacillus plantarum to half of the guys and then party again by us again so the presence of lactobacillus plantarum is influencing the partners choice and what's more important in life well to be serious one minute there are invisible networks probably to be found between animals as well so that the whole point is more complex because also the other animals can believe to you I insist on that those are very preliminary at a preliminary data but we consider so much organisms as independent autonomous entities we by the way it's Occidental thinking people that we are not prepared to the idea that the fact that you and me are sharing the same bacteria can influence our behavior make you and me not behaving independently from each other maybe you can consider it science fiction with a bizarre investigation on a bizarre insect that will never feed humanity except that insects are big competitor for poultry in the future of the food for you but okay let me come to my conclusion I would urge you because this is the thing we feel maybe we are wrong as scientists working on symbiosis I would urge you to think Network and if the dependency between organisms what I tried to introduce you is that you can go further than considering that you are curing organism by including microbes and considering that what you hundred are hollow bones and I think that the tunic store is nicely shown how we can make steps in this direction for poultry but I also told you that all Oh bones our first order approximation of something which is a network of interaction in plant science we see physically this network because of the fungi linked in the roots but in animals there may be such networks as well and those interactions are more less strong maybe you can neglect them in some case but in some other case who knows I'm just opening a tool box which was never explored maybe it's only rubbish inside but we know it after we explore it and if I may if there is only one word to remember of the stork it's the story that there is biotic interaction and this is shaping a lot more than we expected but we tell it in another way I told you that animals can be also seen as microbial ecosystems and it's giving you tools to approach them ok so likely tomorrow we manage animals as microbial ecosystems by the way we know how to do wine we know how to do cheese we though we know how to do mrs. o Romans knew how to do garam we know how to handle microbial community we knew it well before we even knew microbes so it's not a big target but what I told you as well is that ecosystems are open and they are linked to surrounding ones there is no border there is only interaction biotic interaction and that's what I wanted to share with you [Applause]