 Hi everyone thank you for sticking around. I would like to thank Exposure for having me here again tonight and I'm really excited to talk to you for the next 10 minutes hopefully about the work that I've been doing for my PhD. So the title of my presentation today is Comparative Gut Hormone and Gut Bacteria Changes in Patients with Type 2 Diabetes, Undergoing Sleeve Gastric to Me or Ruin Wide Gastric Bypass. Or in other words what happens in our gut following bariatric surgery. Bariatric surgery is currently the recommended treatment for the treatment of type 2 diabetes and obesity. There are many different types of bariatric surgery available today. The two most commonly performed surgeries in New Zealand and worldwide are the Ruin Wide Gastric Bypass and the Sleeve Gastric to Me. These procedures are typically performed in about 45 to 49% of each of all procedures. Both of these procedures result in really significant rates of weight loss sometimes up to 75% excess weight and also really really exciting levels of type 2 diabetes remission. So we see roughly 71 to 72% diabetes remission in both of these types of surgery and so really what we want to understand is how does the gut physiology differ between people who do remit and people who don't. So why is there this 30% who don't remit despite surgery type? So apart from the basic anatomical rearrangements to the gut we believe that there are two other mechanisms that contribute to this type 2 diabetes resolution. They are changes to gut hormones and changes to the gut bacteria or the bacteria that resides in our gut. So as far as the gut hormones we already understand that any changes to the stomach or the gut, any anatomical rearrangements is undoubtedly going to have an effect on the hormones, proteins and small molecules that are produced in or active in those areas and so this is fairly well understood with bariatric surgery. Something less well understood is changes to the gut bacteria. There have been 14 small studies to date looking at changes to gut bacteria following bariatric surgery. There are a couple of common themes emerging including things like an increased diversity or richness of the bacteria in the gut following surgery and also a couple of phyla, genera and species specific changes but based on these studies they're looking at different surgery types, different cohorts, different disease states and a different lengths of study period and so it's really hard to understand whether any of these changes are truly causal or truly contributing to Type 2 diabetes resolution and so this is what we want to do. We want to see if we can pull out something that can be used to have a look at why people do and don't remit from Type 2 diabetes. So the first thing that we set out to do was first compare and confirm whether these two types of surgery have similar remission rates. This is what we expect would happen based on the literature but we wanted to confirm in a single cohort. Secondly we wanted to have a look at whether this similarity is further reflected in similarity to how patients adjust to glucose control and then further their gut bacteria. Do these things look similar between the two types of surgery or are they different? And then finally touching on that final point is can we find something, can we pull something out that's going to help us have a look at people who do and don't remit and why this happens. So in 2011 we embarked on a patient assessor blinded trial so we were looking at the treatment of the bypass versus the sleeve for the management of diabetes in obese patients. So obese patients were with Type 2 diabetes, excuse me, were recruited. They were put on a very low calorie optifast diet for two to four weeks prior to surgery and then they were now randomized to surgery. We saw these patients at two days before surgery, one year after surgery and we're now seeing them at five years after surgery. At all of these appointments they had a myriad of body composition data taken including heights and weights. They also had an oral glucose tolerance test which I'll touch on in a minute and they gave a fecal sample for microbial DNA analysis. So firstly I just want to touch on my first two aims which were confirming that these diabetes remission rates are similar and how glucose control looks following surgery. And so what we see in a nutshell with diabetes remission is we see it is similar. There's no difference between the two types of surgery and it's also quite clearly if not maybe a little bit better reflecting what we had seen in the literature. So at one year following surgery we're seeing 72 to 75% of our patients remitting from diabetes. What about glucose control? So this data was obtained from the oral glucose tolerance test. At time zero our participants are given 75 grams of glucose in a drink and then we take bloods for two hours following that. A couple of key things here. The green is representing the bypass group and the blue is representing the sleeve. These two little red lines are indicating thresholds that are telling us about the glucose control of the participant. So typically patients with diabetes will have a fasting glucose or a basal glucose level before eating of over 7 millimole. We also see that after two hours of a glucose drink, the glucose is sitting much higher than 11.1. So these are key indicators of inadequate glucose control and this is what we see in our participants pre-surgery. So what about following surgery? This is what we see. So the first thing to point out is that all of our participants are sitting below 7 millimole at fasting, which is great. We're also seeing at the two hour mark they're sitting below 11.1 millimole. So this is representing the adequate glucose control. So glucose control has been restored. The really exciting thing here is this insulin. So what we see is the insulin is rushing in following the glucose drink. It says quick quick get out of here glucose. So it sends the glucose to different organs, different tissues and gets it out of the blood, which is why you see that the glucose is significantly reduced at two hours in the following surgery in the in the bold lines. And so this is this is exciting. This is telling us that yes, we do see this glucose restoration, but we already knew that we knew this from the literature, we just wanted to see whether the groups are the same and they are. So what about the gut microbiota specifically? Does do they look the same between surgery types? And is there a difference between patients who do and don't remit? And so this graph is all of our participants who did remit from diabetes following each surgery type. So this is the 70% roughly of our patients. On the left, you can see the bypass. On the right, you have the sleeve group. And although you probably can't read all of the words, what you can see is that there are different changes. So the red bars are indicating increased bacterial taxes. So this is either a specific species or a family or something, something specific that's coming out. Green is representing a decrease. And you can see that the two surgery types are both having increases and decreases, but they're a bit different. But what's really exciting is this Rosberia intestinalis. So this is a specific species or group of species that is significantly increased in patients who do remit from diabetes, regardless of surgery type. So we thought this is great. This is interesting. What about participants who don't remit from diabetes? Which brings me to this graph. So it's the same graph. Red is an increase, green is a decrease. And this is everybody who didn't remit from diabetes as a group. We don't see any Rosberia increasing. In fact, what we see is a decrease in Rosberia species following surgery. So this is interesting. This is something that's starkly different between the groups. And so we wanted to know what is Rosberia? Rosberia is a butyrate producing bacteria. It's typical in a healthy gut. So people who have looked at healthy guts have seen a lot of Rosberia. We know that it is associated with weight loss and improved glucose tolerance. And we also know that it has other beneficial roles in the body, such as influencing colonic motility. And so what we want to do now is take this change in Rosberia, this difference in Rosberia that we've observed, and see whether it relates back to any of our other clinical indices that we have. Or can we even use Rosberia as a probiotic for these patients pre, post or during surgery? So in a nutshell, probiotics are live bacterium that taken at large doses infer health benefits. Typically, they include things like bifidobacterium and lactobacillus, which are known to impart various different health health benefits, such as producing vitamins for the body and regulating levels of other bacterium. So can we use Rosberia? Is there is there somewhere that we can slot Rosberia into this? And it turns out there's a lot of hype about this already. So there are several patents filed that are looking at the use of Rosberia for the treatment of obesity and its associated diseases. So this is exciting. So to wrap it all up. Is diabetes remission similar? Yes. Is the similarity also reflected in changes to glucose control? Yes. What about the gut bacteria? We saw some discordant changes, but really, really excitingly, we saw this Rosberia coming up. And specifically, we saw it coming out in patients who did remit from diabetes, regardless of surgery type, but not in patients who didn't. So I just want to wrap up and thank everybody who has participated, especially my, especially my patients. Thank you.