[Music] thank you to the organising committee for the invitation I'm not a nutritionist I am an immunologist but so I'm going to give a an overview a general overview of gut health from an email a djegal perspective and I'll talk about these the interaction with the microbiome with the host and the immune response and how the immune response is more than just defense against pathogens that is actually involved in regulating not only the gut but other physiological systems within the animal and I'm going to do this by following this this outline I take it upon myself when I give talks about gut health that I need to define gut health from my perspective so that people in the audience have an idea where I'm coming from with gut health and maybe can use this information to formulate their own ideas I'll then follow that up by talking about the components that make up a good gut health that makes up a healthy gut and what I call the intestinal menage tois that being the nutrition or diet of the animal the immune response and the role of the microbiome and then I'm going to go into the communication sort of what we've we've already heard about this morning the organ connectivity between the gut and a couple of other organ systems with the animal and then give some perspectives at the end now most of us have a herd gut health talks and everyone cites Hippocrates that all disease starts in the gut well from my perspective that seems very short-sighted that we're only looking at those animals that are sick from my perspective I think we need to look at it from a more broader perspective that really all health it starts at the gut we have more animals that are healthy I mean we're talking about the United States 9 billion chickens enlightening broilers to go to market every year there's a hell of a lot more birds that are surviving than there and are not sick so I think the the healthy animal tells us a lot more than a diseased animal and the more we know about a healthy animal the more we can get information-wise so definition of gut health we look at the left side of your screen first of all the gut let's break this gut health down into the two words what is the gut well the gut is a tube a tube that starts at the mouth ends up at the rectum so we think of the gut and we're talking about gut hell's of the intestine but really this tube is from the opening to the end and there's microbiota throughout that area yes we concentrate on the intestine because of more functional analysis but we need to keep that in mind that this tube is the length of the animal and because of that it is the largest surface area in contact with the environment it is a barrier that separates those environmental conditions both to eat food materials as well as the environment they're in from the internal organs and because of this exposure to these environmental conditions the immune response is very very pronounced at the gut level in fact more immune cells are there in the gut than any other organ in the body and it just makes sense they're going to be interacting with potential pathogens toxins etc etc the animal needs to be able to respond the I'll talk about in a couple of slides here about the barrier it's not a single barrier the gut is made up of multi barriers yes we think of the epithelial cell barrier that single cell barrier but there are other smaller barriers that play a role the gut also is a natural habitat as we've heard now the first two talks for these microbiota that provide the environment for these organisms to survive and provide beneficial materials to the host then we look at the other side as slide define health well by definition help is an absence or prevention of disease but I think we all agree that when we put our Birds on the floor or put them in the cage that it is not a hygienic environment it's not a sterile environment for sure and so that there's going to be exposure to things that can cause disease that can cause some well to me health healthy a healthy chicken is the ability of that bird to prove to as close to 100% as genetic potential as it can which means maintaining its homeostasis and withstanding those stressors that the environment provides to it as long as it does that the animal is gonna produce we're gonna make money so to me this is good health now the components that make up gut health are many i concentrate on these three as I said I call them the intestinal Minaj's well that being the immune response the immune system the animal the gut microbiota and the nutritional metabolic systems of the host as well and they talk to each other there's an immune inner communication between them that if you affect one you can affect all and that by feeding the animal we are talking the animal is been talking to this immune systems talking to the microbiota and vice versa and all these are produced are talking to each other by various molecules metabolites immune modulators they communicate with each other and we're going to talk about that over the next few slides now amia logically speaking we think of the new response as a host defense protecting the animal from pathogens but at the gut level there is a second response which seems diametrically opposed to what i just said and that is this ability they allow these bugs these microbiota to stay in the gut they don't react against them so there's a tolerance they they allow these bugs to stay there evolutionarily makes sense that these bugs are providing something to the host and the immune response knows that and as long as they stay put and I'll talk about where they are here in a minute the immune response is gonna let them stay there they know that they provide benefit to the host once they leave that area that they're supposed to be and then be all game it's off the immune response can't be generated against them but it's interesting that simultaneously these two functions are occurring that it's not one and then the other that the immune response is constantly surveying determining what's there on what's right now we just heard about the MicroBot ins potential for production and we also heard that it's involved in immune response and it is literally the microbiota the reason that they're there again on an evolutionary scale is that they talk to the immune response they are involved in the development of the immune response they are evolved in the production of the immune response and without the microbiota there as we heard in the first talk in the germ-free animals you do not have the really good response so they are educating the immune response or telling things that are there they're keeping it awake literally keeping it primed so that the function of the response can go forward now I mentioned barriers earlier no mic now here we go we know about the physical barrier of the epithelial cell but if we look at this slide from top to bottom you got the lumen of the gut at the top where dead bacteria feces are flowing through but we have that upper barrier that microbiological barrier where the microbiota state they stay in the upper level of the mucus layer providing a protective barrier against pathogens competitive exclusion is based on this it's concept okay then we have a second mucosal barrier that is sort of a demilitarized zone that is filled with immune mediators such as IgA antimicrobial peptides that prevent many bugs for penny pathogens from getting down to that epithelial layer so there's a chemical layer barrier then we have that physical barrier with the epithelial cell before we go to the lamina propria below it where the immune cells are but I want you to realize that the epithelial cells our component of that immune system they have the receptors and ability the genes to be able to produce the cytokines chemokines and other antimicrobial peptides that the immune system choirs now the interesting thing about this to us from this cartoon you can see that the distance between the microbiota and immune cells it's very small to us but that bacteria it's like crossing the ocean from Europe to the United States so we're talking about five to ten microns distance and yet they talk to each other the question is how how does the immune response talk to the microbiota and that's what will go into the next few slides one of the first ways and we heard about this in the first talking are the materials that the bacteria themselves have on their surface or internally the LPS of the gram negatives the potato glycans of grandpas is a DNA RNA of viruses etc etc these components are constantly being released as the the bacteria the fungi the virus are reproducing and they are keeping that immune response alert because the immune response has receptors directed against it they're constantly keeping the print of the innate response prime through these pattern recognition receptors that recognize these patterns on the microbes so the immune system knows that they're there that can communicate and but at this point in time is not differentiating between a pathogen and a beneficial bug it's just we know you're there we're talking to you we're keeping you aware of what's here so the in Newton the innate response is a sensor understanding what's there so this is one way they communicate through distance the other way is to production and metabolites I think we're all aware that and we as we heard this morning that the microbiota our biochemical warehouses they produce an enormous amount of metabolites that are released that are utilized by the host and waste products that are can be used by the host can be used by the immune system or been shed but these are chemical messengers that allow the bugs to talk to the immune system and interact with the host on a general basis we'll talk about some of these as we go through now the importance of these metabolites shows in this slide that the immune system are totally dependent on their ability to function on these metabolites okay that the development and the behavior the ability of the system the immune system to actually function is dependent on what I've given broken it down here is the three different types of metabolites that are produced through the microbiota first being those that are produced through dietary components we've already heard this morning about fiber dietary fiber being broken down into small chain fatty acids butyrate acetate now talk more about that in a minute tryptophan in the diet produced in dolls which also communicate with the directly with the immune system those metabolites that are modified by the microbiota the bile salts especially this the secondary bile salts which go through the microbiota which have a direct role on immune system at the gut level and then those materials that are produced directly denovo by the microbiota they take byproducts from the diet they change those into materials we're gonna talk specifically about ATP as well as some other materials from bacteria within the gut so this first slide is just an example of the fiber breaking down into small chain fatty acids and what I want the point to get across is that butyrate has enormous amount of effect an immune system it's anti-inflammatory and that it keeps the inflammatory system regulated it's also involved in barrier functions so that the gut barrier is in place okay so it's very very important for multiple functions of the gut we heard this morning it's also involved in energy production by the epithelial cells so butyrate is an incredibly important material that comes from dietary fiber fed to our birds and then a couple of more examples of some other materials that again have anti or pro-inflammatory material depending what we're talking about I mentioned bile salts again bile this material goes through the liver produce a primary BIOS all but secondary bile salts go through have to work through the gut microbiota producing specific secondary bile salts which again have specific functions on the immune response both in terms of most of what I have here anti-inflammatory but some pro-inflammatory activity so that again the menu system is being told what's there it's being regulated by the diet now when we think about that slide a couple of slides ago where I talked about the microbiota being an ATP powerhouse or a biochemical powerhouse one of the byproducts of that by these bacteria function is ATP and there's no way that ATP is all going to be used by the bacteria well immune cells need ATP to function when you activate the immune system it requires ATP to keep that system primed and ready to function well that ATP can be picked up and utilized that ATP produced by the microbiota can be utilized by the immune system and then there are specific bugs within the gut that are amino majid or e the one example I have here is the Bacteroides fragilis which an end product of its biochemistry is this PSA this polysaccharide that has anti-inflammatory materials but there are other bacteria that we know are in the bird that we're just now getting a better handle on it do they function the same way as they as we know in the mouse and human some of the segmented filamentous bacteria that they're in the bird they had the same function in terms of stimulating the th17 the helper material so yes we have the ability to identify microbes that are truly modulatory and the ability potential to modulate them so altogether what this means is that by feeding our animals we are telling the the microbiota that something's there the immune system can communicate with them and then the system itself is able to produce materials that go beyond the gut we heard this this morning that the brain and I'm gonna talk about the lung and the brain here that these other materials these products that are proved Zeus that the gut communicate with these other organ systems and there's more and more literature coming out and Leasing the mammalian systems and the reason to doubt it's going to work in the as well is that the immune system itself goes beyond just protection and by producing molecules can actually regulate the physiology of other organ systems as I have on here this is a list of organ systems that they found already in the mammal that there's a direct interaction now we're a little bit behind in poultry so we can ask these questions is this occurring and I think common sense says we're probably going to be able to find the same thing maybe not to the state that we're finding in mammals but there's no reason to think that we can't so that there is a networking system as we heard about in the first talk internally internally between the organ systems starting at the gut so if we look at its interaction first of all with the brain they gut brain axis we snow that in the gut besides the metabolites that are produced there's all sorts of neurotransmitters and hormones that are being released in response to the gut in response to the microbiota their microbiota producing these things we know the microbiome produced neurotransmitters which talk to the brain through the center through the enteric nervous system which through endocrine cells within the gut and they communicate with the brain until the brain what's going on at the gut so if we do have a disease state the brain is aware of it and that the brain can then say okay I'm going to help and specifically this by a dis bi-directional communication the brain receives signals saying there's problems and that I may need to increase motility of the gut may need to decrease motility may need to cause immune cells direct interaction with immune cells there at the gut to produce materials that are beneficial to the animal at that gut level so there's bi-directional communication between the two organs are there through materials produce at the gut level talk to the brain and then signals sent back to talk to both the microbiota and to the host itself this slide gives a better indication when I'm talking about obviously the production of the materials the new atrophic factors and and transmitters the gut well obviously the barrier function changes all this occurs and talks to the brain the brain then sends signals that can induce the production of more mucus as I have on here as I mentioned motility and permeability okay so there's a direct interaction between the two organ systems this communication is important and think of it as poultry scientists can we manipulate the gut we've talked about we know about probiotics prebiotics that we can manipulate the gut for the benefit of the gut but what's the stop us from manipulating the gut microbiota to manipulate behavior to in effect feed conversion if we can affect the brain there's no reason we can't affect the ability animal to grow with by eating less feed it's not science fiction it's real I believe that within the next 10 years especially to the young scientists this is something that we're going to be able to do that we're gonna be able to increase feed conversion by changing what's going on in the gut have the rectifying spots in the brain the gut lung axis makes sense if you start thinking about the mucus immune system there is evidence coming out now that by changing the gut microbiota without any disease in them in the gut that you can actually affect the immune system at the lung and protect against viral infections now these are all papers that were done in mice or in chapel and pigs but again what's to stop us from finding the same type of situation in the bird that by changing the microbiota at the gut level we can change the immune system and the microbiota within the lung why because long as part of the common mucosal system we'd like to think we heard earlier about individuals animals and that really it's a lullaby on well here we have a mucosal immune system that is not a separate system between the gut and the lung and the reproductive system it's one common system so it's not hard to believe that talking to each other each organ system talks to each other you can regulate each other and so that yes we can have negative effects that if we have a dysbiotic condition at the gut level it would have a negative effect at the lung level which would make the animal more susceptible to a respiratory disease but we look at it the other way is that we can talk to the lung by manipulating the gut and get a better system instead of a negative system so for the last couple slides some perspectives from my point of view we've heard about the plasticity of the microbiome already we have a pretty good idea about that we can manipulate the physiological systems of the animal obviously we need to know more about what the diet can do and how we can utilize diet and components of the diet I think that's it's obvious by the number of people here at this meeting but one thing I do want to caution is that the previous talk gave us a pretty good indication why this this next component is important I think we're spending too much time identifying single bugs and thinking that single bug is going to give us enough information to be able to regulate the physiology of the animal I think the work that dr. Collins is doing is going to provide us with the ability to look at functional groups within parts of the gut so that we can identify bugs as a whole as a community and that community is what's important when you're talking about a trillion bugs bacteria per gram of tissue the redundancy the biochemical redundancy is enormous that the you can still wipe out 20 30 percent of those bugs and still get the same function and I think knowing how these groups were together would give us a better handle on how to keep an animal healthy to provide more information about how to regulate the physiology and I give you an example of this this paper that came out a few years ago again it's it's a human study but the upper panel you look at five different of Yokoso membranes plus school samples and you look at the population the bacterial population in those organ systems and those mucosal systems you see that it varies over time okay that yes there may be some core bugs but they vary up and down but look at the biochemical pathways look the function of those mucosal systems over the same amount of time it doesn't change so the bugs can change the population cannot be altered it can change but the function stays the same so I think this gives an idea is that yes we can manipulate the bugs but knowing more about how they work together is going to give us a much better handle on where to go and how to manipulate the system and so that the idea that these metabolites produced by bugs to get working together and not individual bugs working singularly gonna give us a lot more information at this interactive state at that site of the intestine between there those barrier and the microbiota will give us a much better handle on where we need to go what we can do to manipulate it and provide us with a healthier bird that we can all make a few more bucks on and with that I thank you for your attention [Applause]