[Music] I'm going to speak about probiotic why don't we consider probiotic and everything that is known in the in the literature about probiotic have tried meat that scared me a little bit to do a review on that there is so much data that we don't know where to start with and whisper only we decided that I could do something on the effect on gut barrier and information but again the data in the literature is huge so we can with me it's really a general presentation and I won't go into the detail of everything this morning showed you something that I really like about the story of the beats okay getting to down a hill and hopper here and you can get into certain states where you get up to the L and you get into a very very deep valley and it's very difficult to come back to this mountain so the concept is very nice and it's coming in fact from this publication from French research team and the people have in royal story lab where they are revisiting a little bit the concept of digestive health and this is a very simple representation but I think it's quite a very good one it is of course for for human but again it can be easily used for animal it is based on four main components there are the microbiota the mucosal barrier the immune tolerance and the redox balance and these four elements or four component are obviously very very strongly interconnected and when everything is alright I would say they live in ER all the function and in a perfect some viruses however when the animal ology all is meeting some challenging or stresses that can come from the environment or changes or nutritional challenge and other kind of stress these some biases can be disrupted and you get to this critical transition stage where the microbiota diversity starts to be reduced you increase the permeability of the cause a barrier you increase information you increase the oxidative stress but luckily and it is the same for human we are this you can move from this stitch back to the Samba resist this is true only to a certain point where there is no possible return and in this case you get to the stage of all truths and biases well this time you get a very low diversity in the microbiota high increase in the intestinal permeability sorry and a disturb inflammatory response this is a very similar way of representing it some is against the four pillars that you recognize here but what I want to tell you about in my presentation is that probiotics can act as a four level of this digestive health concept so very simply I will go through all the four of this pillar giving you some example of what probiotic can do and it's a mechanism are known obviously I will try to give you some some idea of how it works let's start by the mucosal barrier so we have spoken about that this morning at least and I will take some example from Michael's presentation especially looking at the models she spoke about the one based on Calcutta cells where we measure transit aerial resistance of the cells and we use this model in fact to study what can be the effect of biotechs when you look at the system it's very easy to understand that you're looking at a direct effect of the probiotic on the buyer because there is no microbiota in the system so we carried out a simple study where we stimulate those cells with inflammatory inflammatory sorry cytokine which is l1 and with just a different product we had a positive control that is a plant extracts and we had also three testing materials that are providing all bacilli base so this is a basal level of what you obtain in the GE our way sorry this is a trial level that you obtain with the control cells when you apply the anti-inflammatory compound as a positive control you see that you increase this response but I think the part of the graph that is here is the most interesting and what you see here is that for this 3 bacilli that we studied we we got completely complete different story some best nya are able to increase the ER and this is a case of the strain wesley sub-series 29 784 that is in fact contain comprised in our product Altaria and the two other Bessel either were tested here decrease the ter so the message here is ready to say that first of all probiotic can act directly without affecting the microbiota you can act directly on the earth and also this is a specific others strength specificity not all probiotics can do the same when we look at the mechanism of our property can increase or improve intestinal bile of course I come back to a word I can and other self-described small the people start to look at what can be the effect of probiotics are on tight Junction protein expression a gene expression sorry so here an example of people from the people in USDA where they have challenged animal is LPS so the a broiler chicken the challenge the animal with LPS there were three groups of animal honey more that did not receive so that the clear bar that did not receive an implementation animals that receive antibiotics that is a second bar and animals that received probiotics and what we see for all the measurements all mRNA or gene expression sorry measured here and that probiotics are able to increase the expression of dye Junction gene gene and as well as missing protein gene choose the same level of antibiotics or even more than what we get with Yangtze budgets something that we also this morning is about antimicrobial peptide I think it is very important part of the story when we think about the first line of difference of the animal in its the animal by himself is able to to to inhibit the growth of certain pathogens by using this antimicrobial peptides strategy here it's an example again this time on in vitro study they are chicken intestinal cells there are either incubated with live bacteria so probiotic which is lactobacilli or it's actually eat action inactivated sir bacterial culture so looking more at soluble thermostable compounds and theater look at the expression of defensing which are antimicrobial peptides in in the cell and what you can see easily that the probity can increase the expression of his defensive and the response is even higher when they look at the soluble fraction produced by this probiotic suggesting to me that indeed the mechanism is through the production of metabolites by the probiotic this illustration here is just to say that in addition to gene expression they also showed that indeed the protein or the peptide are produced that's all I want to say about the mucosal Bayardo and the role of probiotic I would like to move now to the second pillar which is tolerance and inflammation balance so I don't think we we can spend hours discussing that but I think it's very clear for everybody the animal asked to tolerate what is beneficial for its grows for its maintenance and everything nutrients all microbiota but of course it has to be able to respond to aggression so this is a very important balance we are this morning by burns that iga are extremely important when we consider the difference against aggression but also they are important when we consider vaccination this is a study where i GA concentration in in the fecal sample were measured after vaccination with live salmonella titus or by following a treatment with probiotic or the combination of two it's a very simple graph but it's very clear to say that indeed the iga production is much higher when the animal are receiving the probiotic and again it goes very well with what don't explain this morning so my provider probiotic you will see spot finally at the end of microbiota at one point is very important for the development of eye the production of IgE when comes to inflammation I'm not a monologist and I won't going to the details some people do that very well but it's very important there is one pathway that is quite well known now by everybody as a pathway that is important for inflammation and this is the NF kappa-b pathway we know that when this pathway is activated there is a pro-inflammatory response so in a recent review I'm sorry it's so small you cannot see anything but I think it's a 2017 review on probiotic and the effects on different signals there is a very nice explanation on what probiotic can do and they describe different strains of lactobacillus here or lactic acid bacteria but also yeast that can indeed limit the activation of NF kappa-b and importantly in this review and I'm doing some advert for this review because I really like it they speak a lot about the metabolites that are produced by the proviso chickens that are responsible for this decrease in nfk by the pathway activation and one some example are for lactobacillus rhamnosus gr1 produce protein such as a deviation factor to you in our own lab as I explained earlier we use again Shimon are sure that what Raquel is using but it's time to look at the inflammation so in addition to look at TR we also look at how the kakuta second response to probiotics and the way we we measure these responses by looking at alleged production so the cells are similar it was an inflammatory component which is mycotoxin this is a level of distress cell so the production of islets by the stress cell when we apply a noon on confirmatory compo GI elites decrease and when we apply the probiotic you see you again that we I don't have the same response for the three of them for I'll tell you for instance we did we did observe a decrease in this in this inflammation however the two are the strain there was more I allayed purchase what does it mean same things and for the TR it means and first probiotic can act directly on the cell without going through the microbiota effect and the second part also is that there is a real strain specificity on on the right here and this is a step further in the study we have started to my we try to elucidate how it works and the first thing that we did is I would say my colleague Lamia had did she separates it in fact to cell as a seated fraction and the soluble fraction from the probiotic culture and what she absurd in fact who gets the effect on both sides today we don't know exactly what was the important compound but I what I think is important is that you notice that at least part of the story is coming from the soluble fraction meaning that part of the story is explained by metabolite production and again Lamia did much more than that and she's going to present that at the conference so I invite you to go and and mr. George listen to her work and she has really investigated all the pathways and especially an F capable okay aren't the Redax balanced now this is interesting one I would say because that's the one that we don't really know when we consider providing there is not much in the literature that shows that indeed probability can enhance redox balance the other turbit I will teach the less documented one have found some reviews and the only thing I want to say here is that probiotic person can carry antioxidant activity just for instance they produce what I call on silky disease such as the superoxide dismutase but maybe the the most important effect might be by their effects on the microbiota or on the O's improve him as a response to oxidative stress but for this part I think that PAVA social I would be much better than need to explain all of that so I leave at that to him for the talk chest after finally so sometime I start with microbiota when we speak about digestive health but I sort it but my feeling is that it's so important that I really want you to finish with that when we consider microbiota there is a lot to say about it but I think the most important to understand is that it's a community it's like us today all different people being communicating all day sharing a lot and hopefully we are in a kind of Samba some viruses as well but when we consider the curtains of microbiota we cannot use another word than some biases they cannot live without each other and you I don't know if it's new concept but it's new to me at least all abeyance what does it mean it means that in fact the fitness of the O's depend on and cannot be seen apart from its microbiota you can not be well as a human being without your microbiota the second concepts that is very important to me is a microbial ecology again microbiota I like to compare to people because it's all about communication it's all about relationship I already talked with microbes sometimes it's very I'm gonna say very basic it's about food see compete for four feet the the cross feed each other as Philip explained earlier you can have more sophisticated signaling tools such as from something which is in fact seniors from one population to another one thing you can grow you can become pathogen it's quite elaborated and other ways you can compete compete for addition and finally we can not forget about the antimicrobial activity which is extremely important when we speak about the community I'm sorry but we are playing almost with guns in this case okay and one thing I like you to remember is that probiotics in fact even if they are not permanent inhabitants of the earth at one point they will be part of this community so they will influence the community sorry just an example of antimicrobial component obviously I took something about the bacilli species the bacillus species in virtuous almost characterized I would say by the production of antimicrobial and anti inflammatory metabolism all best life produce antimicrobial compounds the the only thing that is important to consider is what kind on tomato on of antimicrobials if you can produce is it's very specific on to microbial is it's a specific as you know surfactants are not very specific antimicrobial here is just to give you an example of what we have fun with our strain why I just wanted to speak about antimicrobial compounds we get it's very simple in in a community when there are bacteria yeah when when a population has been killed or reduced its it creates what we call new ecological niche and as you know nature doesn't like on its empty so obviously there would be other communities that will come and can fill this ecological niches in one experiment with our robotic we looked at the effect of of the probiotic under on the microbiota community in in the in the second what we found is that in fact there were not so many changes but there were two r05 between to be clear there were five significant changes at the genera level and two of of them were very very high changes and they concerned to population the first one was revenue caucus which is known to break down on polysaccharide to oligosaccharides and the second one was an increase in the Latino Clostridium which degrades Oracle saccharides and produced short chain fatty acids especially butyrate why I want you to show you this example I don't know if it's true but at least we can I put it dies that the probiotic will favor this kind of population so if reminyl co-accused is producing more oligosaccharide this oligosaccharide will be used anyway so maybe we are going to be used by like notice again so it may be a nice hypothesis that we have to check but for sure it is a beginning of a cross feeding story and cross feeding is really something is very very important and basic for microbial ecology flippers are shown many things for that but I like to add to example and I will take our favourites bacteria the common sobytiya at least for human application we know and we know for portraits true so that we can bacterium person it's I is very important in the time of literate production so what what is this bacterium so we know it's produced which are it philip explains that it's a tricky one it does not grow if there is any kind of oxygen around but it's not tricky only because it does not tolerate oxygen it's tricky because it needs a lot of things that were produced by others one thing that is well Luana is that fecal bacteria presidency uses acetates to produce butyrate acetate aspra do is present in the lumen obviously because commands or bacteria produce acids it but you could easily imagine if I want to increase as it is in the lumen maybe I can just bring a probiotics that produce a lot of acetate and this is nothing portraits that's not an example for poultry but this is something that was some sort years ago by the people working on human application and the probabilities they spoke about was bifidobacteria so this is one case where probability can CrossFit beneficial bacteria in the gut and the more recent work at least for me it's more reason because I didn't know it is that fecal impaction through schnitzel is very demanding in term of vitamin it needs all the vitamins holes almost whereas some other but Jeff isn't in the Gaza can survive because they are producing themself bacteria determine side so for fecal bacteria pristine science that needs folates I would propose why not using some bifidobacteria they produce folate in some of Travon we know that some best lie produce Hebo Flavian again we know that it's reached I mean as our present you know you know certain level in there good but if we want to enhance their growth why not introducing some probiotics providing the right substrate for growth for ficarra bacterium president side so this is the end of my presentation and the and I'd like to give you some key messages as they are very I would say very basic but they are very important to me at least I think it is important that we all understand that digestive health is not only to speak about microbiota mucosa inflammation or redox balance if we do that I think we are wrong we were used to do that but I think it's a time to change we really have to consider that as a whole ok and try to work all together on that we know that provided cheek sorry we know that provide can act at the four level of digestive health something that we found out at least in our in vitro studies is that the effect of probiotic is really strained specific so and probably behind it for me it's more about a function the name of the probiotic does not matter much what is important is what we can do in turn projects in metabolites and bioactive compounds so this is yeah what I wanted to add it to the last point so with that I thank you thank you very much I thank you for giving this interesting presentation and we should have time for one question so which one do you pick I choose choose back and I can take one that is a very quick answer I think there's a direct effect of probiotic occur also in zoos in presence of microbiota yes I don't have example with like his work that we have done but there is many publication in the in human that shows that indeed he always the asari the probiotic can act directly on zeros without changing the microbiota just because they produce specific metabolites what is your team of germination conditioning gets for bacillus based probiotics that's it that's a difficult one because I would say I don't know but what we know is that obviously best I type probiotics it germinates in the gut they are also that are showing and again it's more maybe on the human side with so also kind of provide that even with inactivated probiotic you can get an activity so that could be something that we can explore also for probably probiotics that germinate or not integrate but what we have seen in our in vitro work is that indeed you get more response when the probiotic has germinated okay thank you [Music]