 Hi there, welcome back to my YouTube channel. This is Daniel Rossell here. Now I've done a couple of videos today on the whole subject of functional dyspepsia, which is also known as FD. Now I've been really, really struggling since I had my gallbladder surgery two years ago. As it must be said, a decent amount of post gallbladder removal patients are with just a whole boatload of digestive problems. And probably the toughest of these to treat or fix has been functional dyspepsia. Now functional dyspepsia is a functional gastroenterological disorder. Now to the best of my understanding, the functional part means that there is no obvious physical or organic abnormality that explains the symptoms. The ones I've been having are what's called post-prandial functional dyspepsia. Now that from the Latin means after eating a meal. So after I eat, I'll get bloating and fullness and I'll feel like I'm sort of pregnant. And it's not a lot of fun and it's been going on for two years. So I have been seeing my own gastroenterologist trying to push for answers in the process of trying to fix this unpleasant problem. I came across a functional dyspepsia community on Facebook, a Facebook group. And they're very active, great community. I will put a link in the description. More recently, I started to look for scientific papers. Do doctors actually understand what FT is? Are there treatments coming along in the pipeline? And once I began doing so, one name kept recurring in every scientific paper I read. And that was a professor, Nicholas Talley. He's Australian, so I'm going to just go ahead and call him Nick. And he has done extensive research into gastroenterology, very, very seasoned researcher and doctor, one of the leading voices in gastroenterology research. And his, one of his main areas is in the brain gut connection and in FD. So I decided seeing as he had done a couple of other videos on YouTube, I shot a professor Talley an email to see if he might be interested in having a chat with me to attempt to get a bit of clarity for other FT patients on exactly what doctors understand about this condition and what might be coming in the drug development pipeline. So without further ado, here's our chat. Okay, so we are joined by Nick Talley from Australia. So Nick, firstly, thank you very, very much for taking the time to have this conversation. I know that for a lot of people with functional dyspepsia, this is going to be invaluable because there's still just a sparsity of information out there on the internet, or that's my perception anyway. So you've been involved in the Rome Foundation, which I would love to mention also, because I know not a lot of people or at least there are some people who I believe don't know what exists with this condition. I'd love to get your, your take on, I guess, where the research is now. Because again, we kind of feel that there is unclear exactly what's happening. There's a lot of confusion regarding treatment and people's doctors trying different SSRI drugs and amitriptyline and the other drugs. And much, much, much confusion, I think, is probably the best way to summarize it. So you've done, I know, extensive research into the gut brain connection, functional disorders. So yeah, I just love to hear what you have to say about all this. Well, look, thanks very much for the invitation to join you. And I appreciate that. And I hope this will be of some value to people who suffer with this condition or their families, because this is really common functional dyspepsia, at least one in 10 people around the world. So remarkably common. And what's exciting is I think the research really is advancing in this field. We're starting to understand what's going on in functional dyspepsia. I think the word functional is going to be discarded by the next Rome iteration of the criteria for diagnosis because it's not functional in many, many cases. It's really almost certainly related to some pathology in what's called the small intestine. So where to start? Well, very common condition. We know how to diagnose it. So people present with feeling uncomfortable, full, bloated after they eat. Often there's a bit of pain as well, not always, but often in the sort of stomach area. And it can be quite distressing. Some people can live with these symptoms. It's not too bad. Other people are really distressed, really affects them. It's pretty severe. And, you know, it's an important condition first to diagnose and also to manage. Normally when we look down into the stomach in the upper part of the small intestine, it looks normal, which led to this concept of, well, there's some problem with the muscles or the nerves or the motor function or the sensory function, but there's no real pathology going on. That was the story that people believed for nearly 100 years. But we now know that when you take samples, tissue samples, when you look down with an endoscope, you can actually find evidence of pathology, particularly in the upper small intestine. And that's been the exciting shift in thinking because once that was discovered, and I'm very proud of my group because we really put this on the map, once this was discovered, we recognized that this inflammation, a special kind of inflammation, probably was related to the symptoms, certainly related to the damage you see that the small intestine's leaky, which is one of the abnormalities. We know the nerves get damaged probably from the inflammation that's occurring, and that means we have a target or targets to provide some treatments that really might make a difference. We also know the bacteria in this part of the gut, the small intestine, is disturbed. There is a change in the bacteria, and that's also probably important in the condition. And sometimes people develop this after a bout of gastroenteritis. You know when you get really crook after you have a bad meal, something you've eaten that's really got infected with something, or you catch a bacteria and you get vomiting and diarrhea and become really unwell for a couple of days, that's acute gastroenteritis, and that can set off functional dyspepsia. So it's an exciting time in terms of this condition, because not only can we diagnose it now, but we have pathology and we have new treatments. That's very exciting. To hear that, I mean I think that's encouraging as well for people who kind of feel like there is either it's a dustbin diagnosis, I think it is the common way to describe it, and it's great to know that there is that. Do you think that kind of understanding of where you and your research group are with functional dyspepsia has trickled down to your average gastroenterologist or do you think there's still a lot of sort of misperceptions amongst family doctors and you know perhaps more regional gastros about functional dyspepsia still being psychosomatic and all that? Well I mean we discovered this pathology in 2007, or that's when we published it, but it's taken a long time for people to start to accept and for other studies to confirm some of our initial observations. It always does when you have a big change in thinking, but it's now starting to trickle down, it hasn't trickled all the way down, don't get me wrong, but it's starting to trickle down and these ideas are starting to become more accepted and the approaches are starting to change slowly. But I can take you through the treatments that we have available right now and what works and what doesn't and I can take you through some of the emerging treatments that we are likely to see very soon. So I'm happy to do that, but clearly the good news is you know this condition is common often debilitating condition often a very chronic condition to it you know it stays with people for long periods of time. The good news is we see a real way forward and ultimately with luck cure for this condition is I think on the horizon which is very very exciting. Amazing. Just before we do get into treatments I just want to one quick question. So there's two sub types or from what I understand a functional dyspapsia the epigastric pain syndrome and the post-prandial distress and do you think the distinction between those two types in terms of the underlying pathology let's say and treatment approach is very different or is it really kind of different manifestations of one disease? So it's a little bit complex. The post-prandial distress syndrome is this syndrome where if you eat something you get crook you get unwell you get fullness bloating discomfort pain sometimes that's post-prandial distress syndrome and that's where the pathology that I just described that inflammation in the small intestine is most strongly linked. There's another group with epigastric pain that's stomach pain just below the breastbone and that group is is more complex it's a much smaller group it's not always related to eating it's probably a different condition actually but that is a much less common syndrome than the post-prandial distress group. That's actually extremely interesting because in this Facebook group I mentioned I think the epigastric pain or the people with a lot of pain complaints are over represented so I wonder if the people with the kind of bloating just kind of put it down but as you say it can be incredibly incredibly debilitating. I love that word crook as well by the way I presume it's an Australian word I'm going to have to have to start very Australian. Okay so yes I guess let's get into treatments in terms of what we have at the moment in terms of the treatment options and I guess what's coming in the in the drug development and research pipeline. So look first-line therapy and it's been first-line therapy for quite some time ever since we did some clinical trials on this are proton pump inhibitors these are acid suppressing medications often used for reflux disease for heartburn for example for peptic ulcer disease so you know a common group of drugs commonly use but what's really interesting is that they work in functional dyspepsia no doubt about that and what's really fascinating is their anti-inflammatory they reduce this small intestinal inflammation that you see on those biopsies and we believe based on the accumulating evidence that in fact the reason they work is because they suppress this inflammation not because they're acid suppressing medications so that would be first-line therapy and the proton pump inhibitor safe drug relatively can be used long term if required can be used as needed not long you know not every day but as needed which is also also works for some people there can be side effects any drug can have side effects but relatively safe compared to many medications that we use so that's a good drug to start with and I always start with that drug not everybody responds there's no doubt about that you know some people do not respond so that's what you do first first line for medication if that fails your next medication that you can think about is what's called a prokinetic drug a drug that accelerates the movement of material from the stomach and the small intestine and there is some evidence some people with these symptoms will respond to this group of drugs there are many different prokinetic drugs around the world the problem is the benefits are relatively small and the drugs available around the world very very significantly so it depends on which country you're in to what's available so in Australia very limited options in the United States very limited options in Asia more options we can come back to that but that's a group of drugs that are used and can be helpful as an additional therapy sometimes you add that on to the proton pump inhibitor drugs another option is what's called an antidepressant drug now this is not being used for depression this is being used to help the gut work better and have less sensation going in the wrong direction because one of the problems with this condition is the gut's very sensitive and these drugs are meant to tone down that sensitivity the the best evidence is it's with a very old class of antidepressants in low doses non antidepressant doses called the tricyclic antidepressants so amitriptyline is one of those tricyclic antidepressants and in low dose well tolerated safe relatively and some people find the marvellous therapy some people really respond very very well some people do not respond it's it's unfortunately a little bit hit or miss but it certainly certainly does work some of the other antidepressants the evidence is less clear that they really have a benefit for example the selective serotonin reuptake inhibitors prozac one of those doesn't doesn't work it doesn't work in functional dyspepsia whether you're depressed or not depressed it doesn't help the stomach symptoms so i think that's important to recognize there are some certain other drugs certain other medications that can help some people and we use those sometimes as as additional therapies so that's the drug side of it but i want to emphasize to people diet probably makes a real difference and that's because we believe foods set off this syndrome in some people actually probably drive the inflammation in some people so diet is a very important understudied component so what kind of diets may work a gluten-free diet works for some people we need to understand that better we don't know a lot about it but it seems to help some people some people will use an elimination diet certain foods that they eliminate but there's actually some evidence that again gluten nuts fish and a few other things milk products eliminating those can really help some people's symptoms and lead to relief and then finally a diet that's low in what's what I call fermentable carbohydrates what I call FODMAPS can help some people as well so we don't know as much about diet in this condition we're really beginning to learn it but there's no doubt diet can help and seeing an expert dietitian or a nutritionist can be very beneficial for some patients and I send almost all my patients to a dietitian to help manage the patient with me so diets important medications can help and then stress reduction helps some people as well probably stress aggravates the symptoms doesn't cause them but if you're really under a lot of stress it can be helpful to deal with that issue as well and we believe that the inflammation may be one of the drivers of increased anxiety in some people with this condition that they have increased anxiety and that's actually driven from the gut and that's a really important new piece of information as well absolutely fascinating this idea of this kind of two-way process between gut syndromes causing let's say you know psychological or psychiatric complications and vice versa those being bad for the gut so if somebody wants to find and I don't want to sort of make this about myself but that's kind of what it was for me it started with these gut problems then that can become very very depressing as people find it harder to exercise and do all these kind of you know common health mental health suggestions so if you found somebody in functional dyspepsia who was who had let's say a developed depression or anxiety as a result of this condition would your approach also be to use those older tricyclics or you know to go for the SSRIs and SNRIs and the more modern psychiatric drugs so I mean normally I it depends on the situation obviously if there's if there's depression if and people do get depressed I mean lots of people get depression it's a very common common problem then that needs treatment and we will treat that with one of the newer drugs for example that treats depression as part of the treatment approach if there isn't depression per se then we will probably use something like the tricyclics you know to help settle things down while we're also working on the dietary approach and perhaps some other treatments that I just talked about some people do need combination treatments because they've got a a long-standing dysfunction of their gut and it takes quite a while for it to get back into into into more normal patterns and that's just the way it is okay um so yeah and that's what we do there is some evidence that also you can treat the microbes in the gut that are probably relevant to this condition so you can suppress microbes and we we know that there's a use of what's called a non-absorbable antibiotic a drug called rifaxamen can be helpful for some people with this condition and we do use that sometimes probiotics less evidence about benefit probably there is some in some cases but we're not quite sure what the best probiotic is so that makes it a little bit complex to to treat that okay is there any evidence any connection between this small intestinal bacterial overgrowth soluble unfunctional dyspapsia or is that not really being no there's good evidence that people with functional dyspapsia have increased small intestinal bacterial overgrowth we don't know if that's a primary condition in other words whether the bacteria are driving the syndrome or whether it's related more to the fact that the muscles and nerves don't work properly and that means you get bacteria growing more than you would expect but we certainly recognize the association um and uh there's more work going on to sort out which bacteria specifically may be relevant that's a lot of what we're doing now we've got very exciting work ongoing in this space with the goal of course of treating bacteria that really matter and specifically targeting those to relieve the syndrome and i think we're going to see some really interesting approaches there in the very near future um one one of the interesting questions i got from facebook and i know i know i know your uh your time is short we need to talk about the the drug pipeline but just one very quick one if i may uh is there a connection between functional dyspapsia and autoimmunity so the answer is almost certainly yes interestingly so we've done some work in this um we know that associations of functional dyspapsia include a topic diseases like asthma and allergic rhinitis um and that was a little bit of a surprise no one had really found that before but there's absolutely no doubt about those associations and a weaker association but still important with autoimmune diseases rheumatoid diseases in particular and we we we don't fully understand that linkage but we suspect that again there is um auto antibody production probably from the inflammatory process that's what we suspect is going on are possibly driven by the bacteria that i'm i'm talking about that may change so if that's true and that's a hypothesis we're still testing and and following um that's really exciting as well because it might imply we might be able to treat certain autoimmune diseases as well through the gut so again pretty pretty stimulating stories are coming out from the work being done okay so in terms of what's in development so this drug that i uh wrote to you in an email i kept coming across and i think a paper you wrote you wrote akotiamid i'm not sure that's the correct pronunciation that and other drugs what what are things looking like in terms of what's coming down in the pipeline so akataya mines are very interesting drug it's available in japan and india only to the best of my knowledge at the present time it's been tested in clinical trials it is able to do something that's very important it relaxes the stomach which actually allows that feeling of fullness and uncomfortableness and and pain to sort of settle right down um and we think the reason the stomach doesn't relax properly is the small intestine affects the stomach and that's why the stomach doesn't relax so the drug works by not working on the small intestine works on the stomach and it's fairly effective um the clinical trial suggests some people will even get complete symptom resolution it'll go away the symptoms not everybody it's a small number but those who do do very very well so it's a good drug i don't have any clinical experience with it myself as it's not available to me in australia or in the united states um but it's certainly a drug that i think may end up coming more becoming more widely available and it seems to be reasonably well tolerated which is again a good a good piece of information to have so that's a new drug relatively new that is actually available in some places there are other drugs that target the inflammation in the small intestine turn off the inflammation and so there are some really interesting new drugs that can literally just switch it off and they look very very promising not only for the inflammation but also for the symptoms that people develop with this syndrome a lot of work going on in this area a number of companies are working to develop drugs that will follow this line um and i think that looks very exciting particularly for people with really severe functional dyspepsia where you know that's the group you target these drugs to in my view okay and i mean i guess that the million dollar question for sufferers is obviously there's a clinical trial process there is the process of fda approval ema approval these things sound wonderful but how long is it going to be before our local gastroenterologists can take out his prescription pad and write us up our acotia meter or a small a small intestine modulators so look i think it does take a little while for these things to work through the system so it takes some years to get through a clinical trial program there is a clinical there are a couple of clinical trial programs underway right now a couple of really quite close to finishing so that is exciting because that could lead to earlier approval you know because they're already well advanced but it depends on the results of those studies of course to see where they end up so i think we're a little way away from that in the meantime repurposing drugs already available is work that we're doing and other groups are doing to see whether we can make a difference with drugs already that are available and again don't forget diet is a very important piece of this and uh that's uh cheap safe and available so again very important for people to recognize there is a lot of overlap in the group between people you know suffering from GERD and IBS and these other conditions do you think the there's any link between these two and is there a connection it's almost certainly there is a connection people with functional dyspepsia are more likely to have irritable bowel syndrome particularly the diarrhea subtype of irritable bowel syndrome more likely to have gastroesophageal reflux disease with bad heartburn and sour taste acid taste coming up and damage to the esophagus we know they're linked but what's really interesting is this small intestinal inflammation looks like it's one of the drivers for some of these patients with these other conditions and what's exciting about this is that means we may have some new treatment options for these diseases too and that's an enormous number of people around the world who might benefit from new approaches so we're very excited about this idea that because we know what's going on at least in some patients with functional dyspepsia we might be able to make a real difference perhaps even a curative difference to patients with other conditions that are also remarkably common and burdensome. Why thank you Nick Nicholas so thank you very very much for your time I think just on behalf if I can speak for other people with FD I know that this interview or I hope this interview is going to be tremendously appreciative just to know that there is an understanding a growing understanding in terms of what's causing this treatment options is very encouraging so thank you very much for taking the time today to share your clinical experience and your research experience with me today. So Daniel thanks very much for having me it's been a great pleasure I hope my comments have given people some hope if nothing else about this condition and related conditions it's really exciting you know you know what what what excites me in particular is the idea that we get we're making advances that may change practice and make a real difference to people and patients so thank you very much. Thank you very much Nick so that was my chat this morning with Professor Larius Nicholas Talley through and through Australian and one of the leading research gastroenterologists in the entire world so it was an amazing privilege to be able to ask him some questions about functional dyspepsia and I just have to say that listening back I just spent the last hour editing that interview not nothing was taken out just editing pauses and I think there is a great deal of scope for hope in Professor Talley's comments just in terms of various ways if you're also really struggling with FD and maybe not getting answers from your doctor that dietary interventions a few different drugs to be tried and for those for those of us not in Japan or India hopefully not so much longer left to wait before those those newer drugs that are more directly going to treat FD are going to come to market so that's definitely room for hope there as well thank you very much to the functional dyspepsia Facebook group for sending in questions I unfortunately didn't have time to ask Professor Talley every one of those but I hope that for FD patients this was useful I just want to say one very very personal thing close to my heart because we did talk about psychiatric comorbidity and all that kind of stuff and I just would say that the last two years dealing with this has been so so mentally challenging and I would just encourage anybody to get help in that respect if they need it because there's often a feel that if you do that you're kind of admitting it's all in your head or even if your doctor seems to take that attitude that's not a good reason not to get help if you need it because I it's it's all going to help and it's all related and Professor Talley's research into that called Brain Connection has just kind of elucidated that so thank you guys for watching and and hopefully more videos coming out about FD on this channel at some point in the future