 We humans are a complex ecosystem that consists of microorganisms such as bacteria, virus, fungi and our own cells. So these microorganisms live in us, they live on and around us and they contribute to make who we are. If we compare the microbial cells to our own cells, we have more microbial cells in our body compared to our own cells. As far as the genes are concerned, we have more microbial genes. Compared to our own genes, therefore, these microorganisms are very important and they play a very critical role in our health and diseases. We first get main dose of microorganisms at the time of birth and factors like type of delivery, type of feeding and environment, antibiotics, illnesses, they all contribute to make the make the microbiome profile in the early stages of life. Until age of three years, our microbiome changes a lot and it becomes more stable and represent at that like microbiome at the age of three years. Therefore, early life microbiome development is very important factor which determines our health and diseases. Sometimes, unfortunately, adverse life events in early life can have a negative impact in the health and development. So one such early life adverse event is preterm birth. Preterm birth is a common event and preterm babies are the babies who are born at less than 37 weeks of gestational age. In our research, we mainly focus on the children who are born at less than 32 weeks of gestational age. They are the children who are born at very preterm. So these children have higher risk for the development of adverse metabolic profiles. So 12 years ago, in 2004, Professor Paul Hoffman and Professor Wayne Cutfield and the research group found that in very preterm children, insulin works less compared to term children. So we know insulin is a hormone which is important to reduce our blood glucose level. So in these children, they had reduced insulin sensitivity and when these children become older, they have higher risk for the diabetes, blood pressure, high blood pressure, bad lipid profiles and obesity, leading to the risk of having cardiometric diseases. Some of the factors like intravenous nutrition, dietary fortification, infections, diseases, antibiotic, medicines like steroids in early life stages of these preterm children can be indicated in the development of these adverse metabolic profiles. However, still we don't know what causes exactly these changes in these children. Just after the birth of these preterm babies, they have delayed and altered gut coronation. However, little is known about the microbiome development when they become older. So in our research, we ask three questions. One, whether these children have less insulin sensitivity compared to term children. Secondly, we ask whether these children have different bacteria in their gut compared to term children. Thirdly, do these children have bacteria and these bacteria do different things in the gut of these preterm children compared to term children? So to answer these research questions, we recruited 50 children who were born at very preterm and 51 term children. At the main age of 7.5 years, we collected data such as weight, height, insulin sensitivity, blood pressure, fat and muscle mass, diet and physical activity. So as I mentioned before, we were interested in looking at their gut microbial composition and the activity. For that, we collected fresh stool samples from these kids and I extracted the genetic materials, microbial genetic materials such as RNA and DNA. With this particular technique called next generation sequencing, I sequenced these genetic materials and found which microbes are present in the gut of these children and what these microbes are doing in these children. So from the data that we collected, we could not see any difference between preterm and term group in terms of sex ratio, weight, height, BMI, total body fat percentage, blood pressure and lipids. However, when we looked at how insulin works in these preterm children, we found that in our very preterm children have reduced insulin sensitivity compared to term children and this data is consistent with the previous findings. Then we looked at the bacterial population in these children and then we found that this particular micro-organism called pre-vortellar copri is higher in preterm group compared to term group. So pre-vortellar copri percentage is more than double the percentage of pre-vortellar copri in term group. So in the literature, it has been found that this pre-vortellar copri is associated with glucose intolerance and diabetes. Then we looked at the active bacteria in these children. So as you can see, the bacteria which are highly present in preterm children are shown in green bars and the bacteria which are highly present in term group are shown in red bars. So in this preterm group, they have a higher percentage, a higher number of colinselar species and some other related species and they are associated with adverse lipid profile and impaired glucose metabolism. And some of the species, for example, allyl strips species which are highly present in term group are associated with protein rich diet. So then we wanted to look at their diet and see whether there is any difference in the diet in these two groups. When we looked at the diet, we could not see any difference between preterm group and the term group in terms of dietary parameters. So then we looked at the bacterial activity in these children. So as you can see, although there are different bacterial activities, different between groups, we mainly observed that this arginine biosynthesis pathways are highly expressed in preterm group compared to term group. Arginine is an amino acid and it is important for several metabolic functions in our body. For an example, arginine is a precursor and it is important to synthesize nitric oxide and arginine and nitric oxide pathway is important for some of the functions of insulin. In type 2 diabetic patients, it has been found that this arginine and nitric oxide pathway is impaired. So this gives us a clue that in our group, in these very preterm children, higher expression of arginine biosynthesis pathway can be linked with the adverse metabolic profile. However, we still don't know the mechanisms. So from the data that we have so far, we can conclude that these preterm children have reduced insulin sensitivity and yes, they also have different bacteria and they have these bacteria are doing different things compared to term children. So what is next? So it's very interesting to follow up these children and see how their microbiome changes over the time, how these microbial activities are going to be changed over the time, but then we have to wait for that. So in this particular study, temporal and discrete sampling of stool samples have shown that in healthy individuals, over a five-year period of time, 50 to 60% of bacterial strains stay the same. So it is clear that environmental and developmental factors can shape up our microbiome. However, there is less information about the microbial stability in an individual over a very long period of time. So in that regard, we got a great opportunity to analyze the stool samples from the famous artist Billy Apple from the stool samples present in toilet tissues collected in 1970 and 2016. So we analyzed those samples and found that 55% of microbial strains remain same after 46 years. And this is very interesting and this data is consistent with the previous predictions. So although Billy has been living in different countries and he's been exposed into different environment, having different diets, this gives us information that there is a genetic component which can play a role in maintaining and in selecting microbial composition in Billy's samples. So with that, I would like to conclude my presentation acknowledging my research team, my supervisors, Professor Wayne Cutfield and Dr. Justine Osulevan and all other research team members, collaborators, funding bodies, last but not least, all the children and their families who gave the wonderful contribution to our study. Thank you very much all of you for the kind attention.