 Thank you Ranan and thank you very much to the organizer for inviting me for a very challenging talk because to make a link between what we heard already and especially from the last speaker and the fascinating world of microbiota and I would like to present to you some insight some new insight in the field and my talk will be divided in four parts regarding the first point which is something new to programming the disbiosis microbiota and feeding and finally how to modulate microbiota the first point is very important since the last decade indeed there is no longer consideration for this view of the microbiota or microflora that was the wording previously indeed it represents only 30 percent of the bacteria in our gut because they are cultivable and since the onset of metagenomic and one of the first work from the MetaEat network program published in Nature in March 2010 the view on intestinal microbiota our commensal flora did change and today we have to consider the following there are three dominant phyllo and the largest one is probably the bacteroid detest the second one is actinotopacteria and the third one is a femicutus and you will see from this wording that it can occur some change in this phyllo and the second point to be considered is that the microbiota is representing more than 10 times 10 times more bacteria than we have cells in our body the second point is that the total weight of the microbiota is over passing the human brain and the second is that the microbiota in our gut has a potential for genetics which is great and greater than our own potential and for all this reason today our view on microbiota is that is more or less an organ and it's an organ because it can be also transplanted and we will see which type of application we will have the so it's an important point that the microbiota change over aging indeed their number of species according to age is changing from births preterm babies to the seniors and the microbiota diversity is changing either and the diversity with age is changing with greater proportion of bacteria this this time the abundance of clostridium groups increase anti-bacteria population and lower number of bifidobacteria which is a very important bacterial species and what is the reason maybe antibiotic use low fiber diet or any other factors but probably one of the actor in this pathway is the short chain fatty acid change we will go back to that and if we go back now to the beginning of life after birth there is a bacterial colonization with implementation of the microbiota and it's clear now that this colonization may be influenced by several factors the term of pregnancy the root of delivery the hygiene of the neonatal environment the maternal bacterial gut microbiota the diet of the infant and the use of drug like antibiotics or ppa interestingly if you look at this cartoon there is a repetition of sea delivery cesarean delivery in the world and the winner is south korea almost 40 percent of births are from c-section and not the loser but i do consider the best in netherland is with 13.5 delivery by c-section and mexico u.s and other countries are in the highest range of c-section and if you look at the influence of c-section on the bacterial colonization you may understand which type of consequence and here on the left in a blue there is a c-section and as you can see it provides difference in the microbiota implementation whether this change these differences are reminding over life it's not clearly known but it seems that it can last several years and interestingly there is a link between the c-section delivery and the occurrence of some disease like diabetes type one and type one is related to immune disorder and autoimmune disease there is no data showing today that there is a link between c-section and type two diabetes but there is a recent study or two years ago published showing that the occurrence of obesity in a preschool children is influenced by the c-section as you can see the c-section in red is significantly more frequent in the c-section delivered baby and even if you adjust on the bmi of the mother the difference remain one other factor is related to breastfeeding and it's well known for many years that breastfeeding is influencing the gut microbiota and if you compare with breastfed and formula fed there is difference especially regarding the bifidobacteria and recently it was shown that by comparing formula rich in protein and low content protein and breast milk there is difference in the occurrence of overweight and obesity in childhood but the reason are protein or microbiota or both and interestingly in the paper there is no real approach of the gut microbiota change according to the formula and finally the first message of my talk is regarding the difference that could occur from birth between children indeed those are different immediately after birth according to the term to the c-section to the antibiotic or ppi use and to the formula feeding and it's clearly known that early change may have consequence for immune system development metabolism and health and it's a reason I am allowed to talk about microbiota programming as we know the metabolic programming there is probably today to be considered the microbiota programming what is this this biosis and occurrence of disease the goal of this implementation is to have the peace the peace between the host and the commensal microbiota and that provide homeostasis and physiological development but sometimes because of several factors as mentioned before it can have a loss of homeostasis it's called this biosis what is this biosis this biosis is the loss of a equilibrium between protective and deleterious bacteria and that can be caused by mode of delivery unadapted feeding acute gastroenteritis antibiotic use or abuse and ppi use and there is clear evidence today that perturbation of intestinal microbiota by antibiotics or ppi are clearly established on epidemiological point of view and there is also studies focusing on the onset of inflammatory bowel disease in relation with antibiotic use which is a very important issue and if you look at some experimental model and that is Laura Cox work and you can see that by receiving nothing or 16 weeks or 20 weeks of antibiotics in the mouse model there is change in the body composition and especially in male that means that antibiotic microbiota and body composition might be related and what is clearly established today are the perturbation of intestinal microbiota as a possible factor of disease and you can see that is recognized today that obesity and type 2 diabetes are on the list and today the view of the microbiota and the health and disease is very large involving several organ and function like the adipose tissue the liver with a nash non fatty acid liver disease and the atherosclerosis sponcratic disease etc and of course the GI tract and we have to add the link between microbiota and allergic disease IBD motility disorder and IBS and probably many others and to go in that direction there is clear evidence for now several years from the meta eat studies that there is difference if you compare sorry if you compare the microbiota of ulcerative colitis patient there is not the same microbiota and especially in ulcerative colitis patient there is a loss of diversity and in obesity there is change according to the degree of obesity as assessed by the BMI which is clear that again microbiota and obesity and body composition are related we will see why and how and what is known for again many years that there is change according to the status obeys or non obeys involving the proportion of femicutus and bacteroidates and indeed the starvation make the change and we don't know exactly if change in microbiota make obesity or change in obesity make change in microbiota which is a question but interestingly there are model and animal model of course of fecal transplantation and you can have an obeys mice mouse which become sin lean and the contrary just by changing the fecal microbiota and there is today evidence that fecal transplantation with obeys mice faces into lean germ free mice run the 20 percent increase in visceral fat compared to the the base line and just after two weeks of transplantation which is absolutely fascinating to be able to transfer through the microbiota a metabolic disorder and now there is a body of evidence from several paper published in very very prestigious review like nature suggesting a link between microbiota and metabolic disease and indeed it was shown by Carlson that in obeys there is a reduced church and fatty acid butyrate producer and a decrease in rosy burial species and also the famous fecalibacterium prosnity which is also involved in Crohn's disease interestingly and there is an by the enrichment by using lactobacillus casserole and streptococcus mutants in sample as predictive value for developing insulin resistance but there is also predictive value of the microbiota and indeed that is to show you that by stratifying the according to the glucose tolerance there is predictive value and that is normal glucose tolerance and that is type 2 diabetes and in the triglyceride level and C peptide and that is representing the microbiota that mean change in microbiota are predictive of the onset of type 2 diabetes and more over it's very interesting to see that again by transplanting feces you may change the profile in term of peripheral insulin sensitivity and again by performing allogenic gut microbiota infusion according to otologous gut microbiota infusion you have changed ear but not ear obviously and the same on hepatic insulin sensitivity which is really fascinating transplanting the feces and improving the metabolic status. Our microbiota is also in France certainly by feeding and there is a lot a lot of paper suggesting this link according to the geographical localization the feeding is not the same in Africa and South America or North America or Asia but interestingly in this recent paper Nature there is a link between the type of feeding and here are listed the cheese and dairy product feeding and according to the meat and the salami or protuto and there is change in bacteria and fungi repetition within the commensal flora and some strains are pointed species and strain are pointed to be changed by the mode of feeding in the same paper there is a link established between two types of consequence of feeding on microbiota and indeed on this part you what is called the putrefactive commensal flora and here the saccharolytic in green and the saccharolytic is clearly influenced by the production or the non-production of short chain fatty acid and especially butyrate I think feeding microbiota and short chain fatty acid are related and that is an interesting work showing that according to the type butyrate acetate or propionate and according to the type of population is a normal population that is a short stay in a hospital and that is a long stay in a hospital and you can see that the change in the short chain fatty acid production probably influenced by the type of feeding especially during long stay in hospital what are the short chain fatty acid there are three main acetate butyrate and propionate and this short chain fatty acid have a lot of function by increasing the mucosal circulation on the level of the colon especially stimulating sodium and water absorption etc but they have also metabolic effect and indeed the short chain fatty acid produced within the colon are partly used locally but are partly absorbed and propionate and acetate reach the liver and peripheral organ where they are substrate for glucogenesis and lipogenesis but more recently it was pointed the fact that short chain fatty acid may control some colonic gene expression modifying several functions and especially in terms of intestinal permeability that means there is again link between microbiota short chain fatty acid intestinal permeability and finally inflammation and to summarize and having an overview of the relationship between gut microbiota and immuno metabolic disease as mentioned yesterday very brilliantly there is a view on considering that stays the genetic background the type of diet the medication like antibiotic or ppi and altering the microbiota and as a consequence it could have changed in specific bacterial strain like proteasin or rumino or some other and that induced change in intestinal permeability leading to endotoxinemia with inflammation and on the other hand altered short chain fatty acid production that influence lipid and glucose metabolism and inflammation and that is a very important global view even if we don't know exactly today what are all the player but one of the most important player is again microbiota of course and short chain fatty acid to induce the so-called since yesterday of immuno metabolic disease in summary the type and mode of feeding may alter intestinal microbiota it affects the production of short chain fatty acid induce change in intestinal permeability and inflammation and in turn short chain fatty acid are influencing glucose and lipid metabolic in the liver how to modulate intestinal microbiota when facing or for preventing any disorder mimicking the normal intestinal microbiota of breastfed infants it's logical and maybe achieved by several approach and that is a summary of this very brilliant lecture of Marlowe Fitzberg this morning and I will not come back on this very fascinating history of dairy product and fermented product but today in the current millennium there is at least three or four approach the probiotics the prebiotics the symbiotics and the fermentation product and probiotics are well known as for life and life microorganisms which when consumed in adequate amounts confer a health effect on us etc it's a WHO definition and many many spaces and strengths are known and there could be and mostly are bacteria but some are fungi and the mechanism of action of probiotics are very well known competition with gut bacteria acidification which is a very important issue and production of different factors in terms of also vitamin and trophic factors and today probiotics are recognized are efficient and as assessed by meta-analysis in different fields acute infectious diarrhea, antibiotic associated diarrhea, necrotizing enterocolitis intestinal functional disorder. There is no clear evidence in metabolic disorder but there's another approach which is prebiotic which is not bacteria there are non-assimilable food ingredients that has beneficial effect in human or animals by stimulating selectively one or more bacterial species of the microbiota and human milk is probably one of the best source of prebiotics sorry prebiotics and what about the fermentation products which is the topic of today many different wording for yogurts and as mentioned this morning there's also difference in the habit and the culture in consuming dairy products like yogurt there are many wording but only one definition and yogurt is a coagulated milk products that result from fermentation of lactose in milk to lactic acid by two different specific bacteria lactobacillus bulguricus and streptococcus thermophilus it's a codex alimentary use definition and as mentioned before by the previous speaker there seems to have relation between the incidence of type 2 diabetes and the consumption of dairy products and especially yogurt I will not come back on that but I would like just to come back on several studies this one suggesting that the consumption of 200 grams of yogurt per day in certain patients compared to no non-consumer make difference in microbiota in terms of detection of lactobacillus bulguricus anterobacteria level certain galactosidase activity and bifidobacteria which are positively correlated with the amount of fermented milk ingested and we know very well that bifidobacteria in the microbiota are very important bacterial species there are also data regarding lactose intolerant subject in relation with the contribution of yogurt and that is also an issue for the daily life of some of our in the population and recently it was published a systematic review paper by using many many database and 61 paper was selected and all indicated that there are differences in microbial composition between obeys and non-obeys patient and in that paper the review approach by using probiotics prebiotic and diet change and the result is that growth of bifidobacteria is clearly related with weight reduction adipogenic effect of diet intestinal permeability and inflammation marker I mean modulating microbiota in the population general population including the use of and the consumption of yogurt may influence the microbiota and finally the metabolic disease and recently and it was published a paper suggesting the use of probiotics prebiotic or symbiotics in elderly fecal microbiota and as you can see this construction may change the lactic acid production acetic propionic and butyric acid involving the short-chain fatty acid modulating the microbiota may change short-chain fatty acid production and finally the metabolic disease and probably the next speaker will go on this paper which is fascinating nothing to do with metabolic disease but by consuming yogurt you may change the emotional response to a woman and if you compare the the control group the placebo the non-ingestion of yogurt and those who ingest yogurt there is a difference in the emotional response as shown on the functional MRI and it's very interesting to make maybe another link between change in emotional behavior and change in feeling habits and in conclusion I would point the fact that intestinal microbiota may be modulated by probiotics prebiotics or fermentation product influencing the immune system the gut brain axis but also the metabolism and in conclusion microbiota implementation is crucial as suggested by the microbiota programming these doses may be related to disease state like IBD allergy IBS etc feeding alters microbiota short-chain fatty acid production and in turn metabolism fecal transplantation offers a new approach both in animal and human for supporting the effect of gut microbiota short-chain fatty acid intestinal permeability and inflammation may act synergically in modifying both glucose and lipid metabolism on the level of the liver and probably the tissue and adipose tissue experimental and epidemiological data have demonstrated links between microbiota obesity and metabolic disease microbiota modulation may be achieved by using pro pre or fermentation product and I would like just to summarize the importance of this gut microbiota in terms of programming and homeostasis in order to prevent any other disorder thank you for your honor