IBD (Crohn's Disease and Ulcerative Colitis): Causes, Symptoms, Treatments and Studies to Find a Future Cure

Hi, this is your host Lindsey Parsons with The Perfect Stool: Understanding and Healing the Gut Microbiome. Today on the show, I have Dr. Charlie Leese, who is a consultant gastroenterologist at the Western General Hospital in Edinburgh, Scotland, and a researcher at the University of Edinburgh specializing in IBD, or inflammatory bowel disease. And he's currently running two major studies that aim to determine the environmental mental and microbial causes and triggers of Crohn's disease. Now on to the show. But before we start the show, I wanted to read a reader email that came to me from Robert. He wrote, I just found your podcast in the last few days and I've listened to most of them already. Thank you so much for what you're doing. It's incredibly informative. I've had ME/CFS, that's myalgic encephalomyelitis chronic fatigue syndrome for 20 years since age 28.

I've—

I never noticed major stomach issues until 2 years ago. It recently became blatantly obvious that maybe all the issues relate back to the gut. I found your pod because I started considering a fecal transplant, but I'm also working with a functional nutritionist in the last 2 months. One quick note that I think people need to know: when the IBS really got bad 2 years ago, a couple GIs diagnosed me with H. pylori. I've Unfortunately, as you might have guessed, they put me through 2 rounds of antibiotics, 4 separate drugs, in what is considered the protocol. It didn't do anything and my condition was quickly getting worse, losing weight, not sleeping, not eating. I was telling my chiro, obviously chiropractor, who I see for lower back issues, and he suggested cabbage juice. I put cabbage in a blender and over the course of a few days I could feel a huge change in my stomach. I was retested for H. pylori, breath test, and they couldn't find it. I also had a scheduled colonoscopy and endoscopy, which found nothing. My IBS was still bad, but it literally saved me at the moment. Maybe you can get the word out on that idea for anybody diagnosed with H. pylori or anybody who has unexplained IBS. It's a cheap and safe therapy. Half a cup of juice twice a day was all I needed. I was tested and found H. pylori free in just one week after I started the juice. Hearing the firsthand accounts of people who've tried fecal transplants is informative. Would love to hear more from those who've gone to clinics in Europe. I'm looking into the Dove Clinic in England after their study on CFS patients was recently published with great results. Thank you again. As someone who's hosted a pod for 6 years, I know the work that goes into it. What's going on in this field is incredibly important, and I'm sure these last 50 years will quickly be considered the dark ages of medicine. Well, thank you so much, Robert. I loved hearing from you and hearing about your story. I have no experience with cabbage juice or why that would be effective against H. pylori, but I'm glad that worked for you. And who knows, maybe it might work for someone else. And yeah, I definitely need to get some more patients back on who've done fecal transplants in clinics and at home. That had been some of the earlier episodes, and I've definitely gotten to talk to a lot of practitioners and scientists since then, and you need to go back to the patients as well. So I will be looking into doing that. You also should know that there is a Facebook group of people who have done or are doing fecal transplants, and it's just called, I think, fecal Fecal Microbiota Transplantation. I can— it's a closed group, so you have to request, and, and it's also sort of a hidden group as well. So I can put a link to that in the show notes so people can find that, and you can post on there and see if anybody has the experience that might help you. So yeah, okay, so on to the show.

Welcome, Dr. Lees.

Hi, Lindsey.

Thanks so much for coming on the show.

Okay, my pleasure. Thanks for having me.

So can you start out with just talking about what IBD is and how common it is.

Sure. So when we talk about IBD, we're talking about inflammatory bowel disease, and there are two major forms: Crohn's disease and ulcerative colitis. And these affect about 1 in 125 people in the Western world, so in North America, in most parts of Europe, and other parts of the developed world. About 1 in 125 people, roughly 50/50 now between Crohn's disease and ulcerative colitis. And these are chronic, lifelong, and unfortunately incurable inflammatory conditions affecting the bowel that typically start in early life, so in adolescence or early adulthood, the teens, 20s, and 30s, and are then characterized by unpredictable attacks of or what we would call flares, typified by attacks of diarrhea, abdominal pain, often bleeding with the diarrhea, with urgency, disturbed sleep, sickness, vomiting, weight loss, profound fatigue, low mood, and a variety of other symptoms too.

Now, there are actually people who die of IBD, correct?

Well, thankfully that is very rare. Most people, the vast majority of people, we would expect to live a normal length of life. So the mortality is thankfully not increased, although there is significant morbidity where, where we see patients or people who live with these conditions who require— most people require some kind of drug treatment. Many times people require multiple different types of therapy, and over time that will then often lead to surgery in many people where the drugs haven't worked.

And the surgery is taking out portions of the bowel?

Yes, so typically resectional surgery where we'll take out a portion of the intestine and usually aim to join bits of the bowel back up together again. But all too frequently, unfortunately, patients then end up with what we call a stoma, where a portion of the intestine is brought out to the abdominal wall, to the stomach wall, and then the toileting, the bowel contents or the poo, as it were, comes out through, through a bag that's attached to the skin on the abdominal wall. That's what's called a stoma.

There's like another word for that, though, right?

A colostomy bag or something like that. Yeah.

So, so it depends if it's the small bowel that's brought out, in which case it's called an ileostomy.

Ileostomy.

Yeah. Or the large bowel that's brought out when it's called a colostomy. And the stoma is the term that refers to the opening onto the skin and then into a bag. So typically people would then call it, you know, have a stoma bag that collects the poo that they would then empty on a daily, on a regular basis. Now it's important to add that surgery can be absolutely transforming for a lot of people that have devastating inflammation and symptoms associated with it. Surgery is not what people would choose to have done. But it can be life-changing and transformative for many people. And so, and having a stoma doesn't need to stop people from actually getting on and living a normal quality of life. It doesn't need to prohibit any of those other functions at all, although it's clearly not what people would choose to have from the outset.

And if that happens, are you able to complete the digestion process in the intestines you have left, or is that leaving you sort of nutrient depleted or I'm thinking about all the neurotransmitters that are produced in the large bowel and that sort of thing.

Yeah, it's very interesting actually, Lindsey. So particularly if you bear in mind, as I'm sure we'll come on to, that the large bowel houses most of the microbiome, the gut microbiome in the body. Most of the bacteria are actually in the large bowel. It appears that for most people who have colitis, which simply means the colon or the large bowel is inflamed. So colon, large bowel, itis means inflammation. So if you have colitis, and we remove the large bowel and then someone has an ileostomy with a normal length small bowel, it appears that there isn't an obvious detriment to normal functioning. So one's normal physiology at that point appears unaffected by this change, which is very curious because we know that the large bowel and the bacteria there have lots of other good functions.

Well, it's sort of like those, those sterile mice, right? Sometimes you have sterile mice that don't have problems that non-sterile mice do, right?

So here's a very interesting phenomenon which is slightly different. So just to clarify, in the first instance, if you remove the large bowel, someone has ileostomy, they still have a lot of bacteria. They're far from sterile. There's a lot of bacteria in the small bowel and indeed often an overgrowth of bacteria in the small bowel, perhaps to compensate for the lack of bacteria in the large bowel. Now, the mice side of things is interesting. Now, most of the work that I do with my group is, is with people where we can derive a lot of interesting observations that teach us a lot about inflammatory bowel disease and what goes on. But we have, from other groups, learned a lot over the years from studying what happens in mice. And one of the early observations that meant that we were very clued up to the importance of the microbiome was that if you took the microbiome out of mice and so-called make them sterile, you— they grow up in a germ-free environment. It's quite hard to do, actually. There aren't very many germ-free environments.

I can imagine.

Yeah. So it's only done— it's done in very specialized laboratories. But in those conditions, it's almost impossible to get mice to develop colitis or inflammatory bowel disease, the mouse version of that. So you can take any number of different genetic or chemically induced colitis models, and there's dozens of these now, maybe 20 or 30 or maybe even 40 different models of mice developing colitis, but do it in a sterile environment where the colitis doesn't develop. And you can usually then actually treat that colitis with Demestos-strength antibiotics in those mice, which, which interestingly has no effect on the human model, which again shows just how different things are. But it does give us a clear clue to the importance of the gut microbiome in inflammatory bowel disease in man.

Mm-hmm. Yeah. Okay. So how often does a typical person with IBD have a flare and how long do they last?

Yeah, it's hugely variable. Typically we might expect, if you just look across the piece, people about 10 to 20% of people to have a flare in any particular year. That will vary enormously depending on what type of disease people have, how long they have had it, and it also then varies hugely about how we define what a flare state is. And this is something that's of particular interest to my group, where we're trying to work out what the causes of flares are and how to prevent them from happening. Unfortunately, one of the things that we see a lot is that there is a big disconnect between inflammation in the gut and the symptoms that a person experiences. So for example, on the one hand, you can have a person that has a lot of inflammation in the gut and virtually no symptoms, and another person might have a lot of symptoms but very little in the way of active inflammation. So for us in the clinical team, in the healthcare team, that provides quite a challenge because it's the inflammation that tends to go on and cause damage to the gut in the long term. So we see this so-called bowel damage that, that accumulates, particularly for people who have Crohn's disease, where the full thickness of the bowel wall is affected. So with deeper tissue layers of inflammation, you see narrowings or strictures that cause blockages, and we see artificial channels that are generated, or fistulae, between bits of bowel and between bowel and skin and between bowel, bladder, for example, which wreaks chaos in the abdominal cavity of the tummy of a person with Crohn's disease over time if not treated early. So a flare state is best defined as a combination of the inflammation and symptoms where appropriate, and our job as physicians is to ensure that we treat both. And that provides a problem if What we have to do is look inside people on a regular basis to see if we can work out what's going on, where, what bit of the disease needs treating and how.

Now, to what do you attribute, you know, a lack of symptoms when there is all that inflammation? Are some people just less sensitive?

Well, no, great question. And it's a paradox that we, that we don't fully understand. It does. It varies depending on, on where the bowel inflammation is. So it's less common in colitis. Where typically inflammation is close to the bottom, close to where you see it come out. So it's much more likely that you will see a patient exhibit bloody diarrhea on a regular basis more frequently than normal. So that, that's clearer. So it's more common to have this where people have small bowel inflammation that's in the middle portion of the bowel. And in that situation, we will quite commonly see, see this develop.

And so, and Crohn's is more up, up in the small intestine typically, or? Just at the top of the large intestine, or—

Yeah, so, so here's an important distinction between the two. So ulcerative colitis only affects the colon. Crohn's disease can affect the colon too, or the small bowel, or both. And it's roughly a third of each. So roughly a third of people will just have colon inflammation or colitis, a third will have just small bowel inflammation, and a third will have both. But Crohn's can affect, um, interestingly, any part of the gastrointestinal tract. So that's any part from the mouth all the way through to the anus. So some people will have quite pronounced inflammation in the esophagus, the gullet, or the stomach, or the duodenum, higher up in the bowel. And that can be extremely troublesome to treat, in fact.

And what then is the distinction between Crohn's and, and ulcerative colitis?

So apart from the, the location or the distribution, as we've just discussed, the other key distinction I guess there are two other key distinctions. One is that Crohn's disease, as I mentioned, affects the full thickness of the bowel wall. And the implications of that are that the inflammation in the deeper layers of the bowel wall can lead to the fibrosis and stricturing or narrowings that predispose people to blockage. And that's why surgery becomes quite common, unfortunately, or the ulcers that penetrate all the way through the bowel wall thickness causing these fistulas. Ulcerative colitis, on the other hand, just affects the superficial internal layers of the bowel. It's also continuous. So ulcerative colitis will always affect the rectum, the bottom end of the large bowel, and then extend upwards to a point where, quite fascinatingly, it will be very rapidly cut off when people have been for colonoscopy, or sometimes, in fact, when we see this when people have had their large bowel removed for ulcerative colitis. It's almost as if someone's taken a ruler and drawn a line down which on one side the bowel is completely normal and on the other side it is very, very inflamed, which is, which is a fascinating clue as to what's going on there, but we haven't managed to untangle that yet. Whereas Crohn's disease, it skips. We see skip lesions, so you see normal bits and abnormal bits that go from one part of the bowel to the next.

So could that sort of ruler delineation in ulcerative colitis be due to the type of bacteria that inhabit that portion of the colon because they might have some exposure to oxygen, like an anaerobic-aerobic question?

So it might do to an extent. I mean, there's no compartmentalizing those different parts of the colon, so the luminal contents will be, you know, washing around this place. So that can't explain that demarcation. The, the anaerobic thing is interesting because there probably is more oxygen that gets into the lumen of the large bowel down in the rectum near the anal canal, as you would expect, it's nearer the outside world, right? And that gets less as you go upstream. So oxygenation probably does have a role to play, but that's not something that we fully understand yet. People have tried hyperbaric oxygen, so sort of oxygen pressure, to try and improve colitis with some benefit.

In the colon, like directly into the colon?

No, no, no, no, no. You put— okay, the whole person sits in a hyperbaric chamber, right, for a number of sessions. Yeah, actually, in my experience, that sits rather better for people who have unusual and complicated Crohn's disease, including Crohn's disease that has affected the skin, so cutaneous Crohn's disease. So we have a handful of people in Scotland that go to regular hyperbaric treatment, oxygen treatment, for that. But this is, this is not a, this is not a usual run of affairs. There are some unfortunate people that have very rare aggressive phenotypes that, that are resistant to all the therapies that we currently have available.

Okay, so what is the current thinking on the cause of IBD?

So Given that what we see or have seen is a rapid emergence in the second half of the 20th century in the Western world, and then over the last 20 or 30 years a similar pattern emerging in previously undeveloped countries as they have urbanized and westernized, we're seeing this incredible lifestyle shift predisposing apparently to the development of Crohn's disease and ulcerative colitis. And on the other hand, we're seeing a very strong genetic contribution to, to both diseases, but Crohn's disease more commonly than ulcerative colitis. To illustrate that, if for example I had Crohn's disease and I had an identical twin brother, he would have a 50/50 chance of also having Crohn's disease. And from that you could suppose that because our DNA is identical, half, roughly half of what causes it is genetic and half is environment. In ulcerative colitis, it's probably more like 75% environment and 25% genetic. And if you put all that together with all the work we've done over the last 10 to 20 years, what we're beginning to understand is that these, these diseases are emerging in genetically susceptible individuals where there is an exaggerated or abnormal immune response in the gut's immune system to probably certain components of the microbiota, and that, that is being driven by the environmental change, which is in turn probably largely what we're putting into our digestive systems, i.e., the massive dietary shifts that have occurred in the last 20 or 30 years in, in the developing world, and prior to that in the now developed world.

And would you characterize those dietary shifts as moving towards more processed foods, more simple carbohydrates, sugar, that sort of thing, or, or something else?

So, Lindsey, this is fascinating. It's an area of active research interest. It's also an incredibly difficult thing to tease out, but I think that the whole weight of evidence across human and animal models, through epidemiological studies and through what we're seeing is that it is a shift to food processing, food additives, perhaps in particular the emulsifiers that are put in to make your food look good and have a— have an appropriate texture. Emulsifiers that you see in ice creams and all sorts of other sweets, but they're rife in all sorts of different processed foods. So that's the one side, additives and emulsifiers. On the other side, there's probably too much animal protein and not enough good quality plant-based fibers. How refined flour and sugar fits into that, we're not quite sure. Lots of people, when they get sick, tend to take more refined sugar in to make themselves feel good, particularly if they're sick with their digestive system playing up. And that skews a lot of the datasets. If you look at people who've already developed Crohn's disease or ulcerative colitis, compare them to healthy people, So to really get at this, it's really of fundamental importance to do dietary surveys in healthy people and then follow people over time and then compare what happens in people who've developed Crohn's disease or ulcerative colitis and those that don't. And that's a big, big problem because although, as I mentioned right at the start, these conditions are unfortunately now very common, in fact, it's still relatively rare for a person to develop Crohn's disease or ulcerative colitis on a sort of annual basis. The incidence remains relatively low.— it's just that the population, society accumulates these prevalent cases over time. So diet is fascinating. And if I were to give you my best understanding of it in a nutshell, it's food processing that has in part been designed to make food last longer, in part been made to make food taste better and look and have a better texture. Plus too much animal protein and not enough good quality plant-based fibers, with a question mark around refined sugar and refined flour too.

So I remember hearing a podcast about those emulsifiers and, and how they impacted the gut microbiome. And now, I don't know if you would know the answer to this, but are there any emulsifiers that are okay? Because I, I remember every gum was, was listed as not great in this podcast. There was a— I remember him saying polysorbate 80. I couldn't remember all of them, but, but I was hoping there was something left that one could use to emulsify because hard to get a good, like, you know, ice cream, for example, without an emulsifier.

The classic is if you Google mayonnaise without emulsifiers and you look at the picture, that comes up right up the list. Mayonnaise without emulsifiers looks absolutely revolting. And no one in their right mind would eat it. The honest answer is we don't know. Is it carboxy cellulose? Is it polysorbate 80? Is it soy lecithin? The animal models that have done this would suggest that soy lecithin might be okay, but really I don't think we know enough about it. These are also very difficult things to study because they are— they're very common in Western food and they're not always labeled particularly well. So you have to be quite careful about it to try and understand what gets into the diet. What I tell my patients is that best way to try and eat if you have inflammatory bowel disease to help prevent the disease from flaring is to eat more of a Mediterranean-style diet where you eat mostly fresh produce, good quality organic fresh produce if you can afford it. That probably helps too, with not too much animal protein, and just try to avoid processed foods where at all possible. It probably, like most of these these things is a quantity. It's a load of whatever is driving it into the gut. And so if you can reduce that level, that probably helps. You probably don't need to cut it out in its entirety. But it's really important to add that a lot of this is still the subject of research. And you'll notice that already I was talking there not just about what causes these diseases based on what we understand about diet, environment, and lifestyle, and there microbiome, but it's also about what we would do to help prevent the disease from having an adverse course. So how do we keep people— how do we get people into remission, and how do we sustain that remission for the long term? And whilst I will have a different suite of drug therapies for different people and try and find the right way to keep someone well with medicines, I think increasingly what we're looking to do is to layer in dietary advice, and in the future, probably microbiome therapies, so that we can help keep people well for the long term. And in that situation, we're largely currently, unfortunately, in a bit of an evidence-free zone, which is why I and others are working so hard to build really big detailed cohorts of people with inflammatory bowel disease followed over time so we can get the data to address these questions.

Yeah, okay, we're going to get to that in a minute, but let me ask you, what are the current— what are the drugs like? Are these mostly immunosuppressive drugs, or what, what are people taking for IBD?

So historically, and when I say historically, we only need to go back 10 to 20 years. Unfortunately, people with IBD used to get rather soaked in steroid therapies that treated the symptoms but did little to actually address the underlying disease process and switch it off, and they did nothing to adjust the natural history of the disease to a favorable outcome, and often rather left people with unfortunately too many side effects. Thankfully, that situation has changed a lot. And so let me just go through a couple of key current details for treatments, and then I'll tell you a little bit about where things are going. So currently, ulcerative colitis for a lot of people, thankfully, is treated very straightforwardly with a type of drugs called mesalazines or aminosalicylates. And these drugs are derivatives of aspirin that are safe, extremely well tolerated in their modern form, given either in tablet form or by suppository or enema through the rectum, that for a significant chunk of people will treat the disease completely. And then they will keep people well for the long term with very little side effects at all. Crohn's disease is slightly trickier because these mesalazine treatments don't work in Crohn's disease, although still unfortunately they're very highly prescribed. And this is because of the difference between Crohn's disease and ulcerative colitis in terms of one, ulcerative colitis affecting just the superficial layers of the bowel wall, and the other, Crohn's disease affecting full thickness of the bowel wall. So for Crohn's disease, we need to adopt a different treatment strategy. And there we're using largely treatment strategies based on anti-TNF drugs. These are monoclonal antibody drugs, or what we would call biologic therapies. So infliximab or Remicade, adalimumab or Humira, or now the biosimilar versions of those which are being used in Europe, which has cut the price of these drug therapies from about $12,000 to $15,000 or equivalent per year to maybe as little as $3,000 or $4,000 per year with effective therapies for these people.

Bioequivalent is just another word for the generic in the US, right?

So, so yes, we're talking biosimilar drugs here. So these are because these are antibody-based drugs because they're biologic. You can't just follow a recipe like you could for aspirin and be guaranteed to have a carbon copy of the drug. And so they're biosimilar. So they're designed to be similar enough, but not identical. But there's now very strict guidelines on how they're produced and how they're then approved by the FDA or the European Medicines Agency. That's been quite revolutionary actually, particularly in Europe, because it's meant that these effective therapies are now available to many, many more people. And what we've learned is that by using these drugs— so there's the anti-TNF drugs, we've got drugs that target other specific parts of the immune cascade, so either TNF-alpha or IL-12 or other aspects. We've got therapies for ulcerative colitis that now target intracellular signaling pathways like the JAK inhibitors. We also have a very neat group of drugs for ulcerative colitis that also work in Crohn's disease that block very specifically the inflammatory cells from getting from the blood to the inflamed portion of the gut. And in so doing, they provide a gut-specific treatment that effectively stops the supply line of immune cells from the periphery to the gut. And therefore the fire, as it were, that was burning is starved of its fuel and dies out and burns out. So there are a number of different therapies we can deploy that will work for at least, I would say, about 50% of people effectively over time, or for at least a portion of the time. But, but there is still a massive unmet need for, for lots of people. Unfortunately, these drug therapies are not without potential risk, but thankfully there is a massive interest and investment from the pharma industry and from biotech as a whole in inflammation research. After oncology, it's probably the top area of pharma investment, and inflammatory bowel disease, Crohn's disease, ulcerative colitis, due in part due to their— how common they've become, are now seen as very big areas for, for investment. So we have a very, very healthy pipeline of drug therapies coming through clinical trials across the world that I believe within a few years we'll see the, the treatment landscape changed very, very positively again. However, it's not obvious that we've got a cure coming anytime soon, unfortunately, just a series of additional therapies that will help, help us as physicians and patients as the most important people in this to treat their disease better.

So I interviewed someone a few episodes back who used FMT to treat her ulcerative colitis and very intensive every day for the first month, I think, and then and, you know, every other day for another month, that kind of thing. And it went on for the space of about a year, I think, and at decreasing intervals. And, you know, it seems to be in total remission at this point with maybe once a week, I think, you know, treatments at this point.

Yeah. How interesting.

Have you encountered that at all? Because I know in the UK that's a lot more available. Like, that's not allowed in the US except for C. diff.

So we've talked about the role of the microbiome. We definitely know it's important. And then so what suddenly appears in to all of us about 5, 6, maybe 7 years ago now was this Dutch study that showed that C. diff can be cured by FMT, by, by a fecal microbial transplant, by stool transplant, a poo transplant. And so that gave us great hope that this might work for Crohn's disease and ulcerative colitis, it might be curative. Now it's not that simple, and I think what it's clear from the data that we have seen so far in ulcerative colitis— and the jury's still out in Crohn's disease— the FMT is an effective therapy for ulcerative colitis. It's clearly not curative, and unlike in C. diff, where one or two treatments is sufficient to cure the C. diff, in ulcerative colitis repeated treatments are necessary.. And so like, like the guest on your podcast that you described there, Lindsey Parsons Parsons, I think unfortunately for, for a lot of people, that's going to be the reality. To my mind, for the moment, this is an area where we need a significant amount of additional investment and that people having an FMT for ulcerative colitis and Crohn's disease should have that at the moment as part of a clinical trial so we can collect the data that we need to study this in more detail.

Yeah, no, I think she was particularly lucky because she had a very healthy boyfriend who could keep supplying, whereas most people don't have someone in their family who can just for an extended period of time continue to give them, you know, samples, and, or, or it's very expensive to go to a clinic and do it.

So yeah, and, and there are lots of unanswered questions there. The donor's clearly critical.

Yeah.

In the success of it. And how do you characterize that? How they best prepped? How, you know, how do you store it? How do you deliver deliver it. Um, is it best given via nasogastric tube? Is it best given via enema or via a colonoscopy, which makes it a much more expensive treatment to deliver? Lots of unanswered questions. It's a fascinating area that we'll see continue to develop.

Forgive this brief interruption, but I know some of you may be struggling with unwanted weight gain, and the hard thing about weight loss is that most of us know what to do, but we just can't seem to make ourselves do it. Or we make ourselves do it for a time but then feel deprived because we've been cutting calories or going hungry or cutting out entire food groups. And after a while, we give up and we binge on what we've been missing and then say, "Forget it all, it's impossible." And that's where a health coach can help. Changing your habits in the long term is the only way to lose weight and keep it off. And amazingly, it doesn't even have to involve counting or cutting calories or cutting out entire food groups. All of my clients lose weight eating to their satisfaction without even thinking about a calorie. And by working with them for 90 days, they have enough time to establish new habits for life and understand what was keeping them stuck so that they can keep losing weight even after we finish together. So if you're wanting to reverse the health impacts of weight gain like prediabetes, type 2 diabetes, high blood pressure, high cholesterol, or cardiovascular disease, or you're just stuck with a post-baby belly 10 years after you've given birth like I was, I can help you. So please email me at Lindsey— that's L-I-N-D-S-E-E lindseyparsons@highdeserthealthcoaching.com for a free 1-hour consultation to see if health coaching is right for you. I coach people all over the country using video chat or phone. I know it's scary to take the first step, but you can do it and it's so worth it.

And I think what will give a lot of excitement in the future, and there's a lot of biotech investment here, is not just FMT of stool, but of lyophilized capsules of FMT so people can take it by mouth, or, or other clever strategies that will take the positive components of the microbiome and then deliver it to patients. But we're still at the point, I think, where we're trying to define what the positive parts of the microbiome are for an individual with inflammatory bowel disease. What should we be aiming towards? What is the microbiome associated prolonged remission in an individual with Crohn's disease and ulcerative colitis? Some of these questions that we're trying to tackle with the work that I'm doing.

Yeah. Well, I, I always feel like though, for looking from the outside of the medical world in, like trying to figure out what components of the microbiome is just a way of, of trying to, to turn it into a pharmaceutical product, really the pure, natural, complete stool, maybe purified down to get out rid of the fecal matter and just have the bacteria. Supplies what's necessary, why, why have to dig it down to exactly what it is other than so that the pharmaceutical industry can profit from it?

Yeah, I'm not sure if that's a cynical view there, Lindsey, or what, but actually, um, yes, I think, I think this is one, I think this is one of those areas where clinicians and patients, patient organizations, charities that fund the work, as well as the pharma industry, need to work together. Pharma industry need the patient cohorts to help us develop what the aspects are. There are aspects of the treatment that clearly we cannot do without the massive biotech investment that's there and available. So to me, it's one of the exciting areas and one of the joys of working in this space is that I can sit at the interface and lead teams of patients, clinicians, pharma experts, academics, etc., working on this area.

Okay, well, tell me about your studies.

Sure. So the, the main part of the study I'm conducting is a study called PREDICT, where we are looking to see if we can work out what aspects of environment, lifestyle, diet, the microbiome, and genetics are associated with disease flare in people who already have inflammatory bowel disease. So this is PREDICT with two Cs just to distinguish it from all the other predict studies that are out there. So P-R-E-D-I-C-C-T. So we're taking a very large group people to get around the massive heterogeneity or the, the variety that we see in Crohn's disease and ulcerative colitis. So 6,000 people in remission, in clinical remission, self-reported clinical remission, where we then start with a detailed survey of their clinical well-being, the treatments they've been on, but also asking questions about their lifestyle, about how they are. So the psychosocial elements of it— sleep, physical activity. We do a 2 diet surveys with a food frequency questionnaire where they are asked how often they've eaten particular food types in the last month and a food diary, a 4-day weighed food diary where every part of the, the food that they eat, every component of it is weighed and jotted down in a notebook. And then importantly, on the 4th day of the food diary, the patients will send us in stool samples by post. This is all done remotely. So we can do this at scale across the community. Stool samples are sent in by post, both in a buffer that we can use to extract microbiome and also in a non-buffered sample that allows us to measure the calprotectin level, which is the closest thing that we've got to a good proxy of gut inflammation level for someone with inflammatory bowel disease. What helps us get around this? But protectin level, see the calprotectin, C-A-L-P-R-O-T-E-C-T-I-N. So it's a, it's white blood cells, neutrophils, are stacked full of this protein calprotectin, which is then released when there's inflammation in the gut wall into the lumen of the gut. So you can then look in a poo sample and measure calprotectin. We do this a lot in clinical practice. We use it to help get around this issue of the disconnect between symptoms and inflammation. So somebody may have no symptoms, but a high calprotectin level, that gives us a guide that there is inflammation smoldering away that we need to go look for and then treat. So in the, in this, in the Predict study, that's a very important aspect of, of what we measure in the stool samples. They also then send in saliva samples that we will then use to extract their DNA. We send that down to the Sanger Institute in Cambridge where the first human genome was sequenced, and then we do whole genome sequencing on that. So we end up with this very exquisite big dataset of the clinical aspects and the clinical phenotypes, the environment and lifestyle and diet, the so-called exposome of an individual, the microbiome from metagenomic sequencing. We look at short-chain fatty acids and various other downstream products in the microbiome too, and the genomic aspects. And then most critically, we then follow people prospectively in a longitudinal manner with monthly follow-up questionnaires, all done remotely, currently for 24 months. We're about to put an amendment in to follow people for a total of 48 months so that we then look to see and pick up flares, clinical flares here where people will then send back further samples so we can measure that calprotectin level and look at the microbiome in a flare state. So this, this is a really exciting, completely novel area, trying to look at how diet, lifestyle, environment, microbiome, as well as treatments and clinical phenotypes affect disease flare in individuals. To do this at scale, we are partnering with a digital health startup in New York called Oshi Health to, to use a smartphone app to enable very slick and complete collection of the, the, all the environmental data as well as the clinical patient-reported outcome measures that we collect both at baseline and at monthly intervals throughout the study. And my hope is that we'll be able to use these methods to not just collect this information, but also to then use it to act on some of the things that we collect. For example, there's a lot of psychosocial aspects that we will document in terms of depression and anxiety and the like. And we can then give people sort of hyper-personalized signposting and interventions to help with that.

So, so with the implication that those things, the depression, anxiety, are impacting the, the Crohn's, or the other way around, that the Crohn's may be causing— yeah, the same, the same outside things causing both?

Yeah, the evidence that's accumulating suggests there's a bidirectional effect here. That both, both poor mental health will have adverse impacts on the Crohn's disease and ulcerative colitis, and that uncontrolled Crohn's disease and ulcerative colitis will have poor impact on mental health moving forwards. In fact, there's a very interesting new strand of psychological health, of positive psychology here, looking at aspects like grit and resilience, which are trainable skills. So we're hoping that we can pick up and identify people who have low grit and resilience scores early in their disease course ultimately, and then we can teach them and train them to have better coping mechanisms so that they will ultimately not just have better mental health but also have a better control of their disease and probably better disease control over time, because it's probably also, um, has significant impact on drug adherence and, uh, and other aspects too. So it's a fascinating and complex area that we're looking into. Sleep and exercise are things that we're currently checking and measuring by questionnaire. But with the Digital Health Partnership, we're going to be looking very soon to start adding in wearable measurement so we can properly track heart rate variability and other physiologic measures. We can look at exercise, not just with simple things like step count, but also geolocation. How close is someone to their, their home and maybe their safe toilet and toileting environment? If they have disease flares, perhaps they're closer, moving less. Can we predict flares from passively collected data on someone's mobile phone before they're even aware there are symptoms, before perhaps even you can measure it in the stool samples? And doing this all at patient's home. We've got technology now in place that we're about to test to check an individual's calprotectin level, the inflammation level at home. So it's delivering care through research and research to improve care, doing these things in parallel, offering value to people. And this is how I hope that we're going to make major breakthroughs in the next few years.

And talk to me a little bit about the heart rate variability and the applicability of that to, to Crohn's.

Yeah, we have no idea because there's no data about this at all yet. I'm a, I'm a fitness nut. I do a lot of endurance sport and have learned a lot about the physiological aspects of that myself. And so, beat-to-beat heart rate variability, particularly measured in the last short period of time prior to, to waking, can have a big impact on recovery and is very predictive of training response and load, etc. And so, one might hypothesize, I think quite rightly, that, that may also be predicting disease flare states and, and perhaps adverse responses to treatments for people with Crohn's disease and ulcerative colitis. This is just hypothesis generating space at the moment, Lindsey. I can't give you any more detail about that at the moment. It may be as simple as someone with active disease has a higher baseline heart rate, but the heart rate variability is, is to me just one of a number of interesting variables that we're looking to start collecting soon.

Well, my understanding just in terms of functional medicine is that, that heart rate variability is one of these things you want because the, the— if you don't have a variable heart rate, the implication is that you're sort of in a constant state of stress.

And yeah, you are, and you don't have, you know, your sympathetic nervous system is just hammering away. There's no sort of parasympathetic sympathetic drive and, and how that affects— this is something that I think is— hasn't yet entered sort of mainstream medicine. But I think it's a fascinating area that to me is being driven by what we understand in, you know, sport and exercise physiology as well as whether other aspects. And there are now good commercial offerings that will allow you to measure this. So I'm hoping that Whoop or equivalent might lend me, you know, 1,000 of their bands to give to my patients so that we can then measure them over time. So you've got to contact Whoop or someone or Aura where we can We can use the, the sleep rings, patients to detect what's going on. I'm very interested in methods by which we can deploy digital tech to passively measure variables that potentially have a profound impact on what happens to an individual over time. We know that when people are well or feel well in particular, they don't want to track, they don't want to input their data on a day-to-day basis. They don't want to have to come to the clinic all the time. But they do want to know what's going on with themselves. And here we're not talking about, you know, perhaps the listeners of your podcast who are highly motivated individuals, very involved and interested in their health. For me, this is how can we impact on everyone who is affected here? I know, for example, so we've, we've just published a big study in Gut looking at the prevalence of inflammatory bowel disease in Edinburgh, which is why I know so accurately about the number of people that have the disease. And when we look at this in a bit more detail, I can tell you that of the 7,000 people who live in Edinburgh, which is a population of just under a million, about 900,000, who currently live there with inflammatory bowel disease, only a third have come to the clinic in the last year or so. And of the people that we admit to hospitals as emergencies, over 50% of them haven't been to clinic in a recent timeframe. So we need to have methods that can enable us to connect with everybody that's out there, including those people who don't want to come to the clinic regularly or, or who are less compliant perhaps with what we would typically have as our expectation for an individual with this disease. That's how we'll make the biggest difference to people across the piece. So if we can implement technology to allow people to collect things passively, then that is how I think we'll make some of the biggest differences across the piece.

Yeah. So, so I, I actually was hooked up to one of those heart rate variability things at, uh, at a functional medicine doctor's office, and of course—

okay, nice—

I had no heart rate variability at all. He said no one does. I'm sure that just, just everybody is so busy and stressed that— yeah. And, and then, and then the other thing that that struck me was I have dealt with SIBO over time and went on vacation and got better. And then I threw it into one of these Facebook groups about gut health and I said, anybody have anything to make of that? And they all said, oh, we all get better on vacation too, which points to stress as one of these potential causes of—

Yeah. So stress or diet that you're eating better when you're on holiday or that you're in the sunshine.

Definitely not eating better.

Well, yeah, but some people do. Or you have more sunshine, that helps. Or you sleep more.

Walking more was about the only thing I did well.

Yeah.

Okay. Okay. SIBO is interesting. SIBO is definitely more common in people with Crohn's disease, with or without surgical intervention. How much of that's diet-driven or not, we're not sure. The heart rate variability, I think, is really interesting too, because just measuring it during the waking day is probably no good. You probably need to measure it at some point in the hour before waking in the morning so it's collected when someone's completely asleep before, you know, when you add in our usual stimulants through diet and caffeine and all the rest. In particular, for anything like me, you know, I need a vat of coffee before I'm anything other than horizontal in the morning. It doesn't matter what time it is, but I mean, that will charge me for the day. And I'm sure that wipes out any of my um, beats per minute variability.

Well, I'm not, I'm not a caffeine drinker actually. So, so, oh, you're not?

Okay.

Yeah.

All right.

Anyway, so do you have any preliminary data from your study at this point that would point towards anything about the microbiome?

So at the moment we've, we've recruited about 2,100 people into the study. We're targeting 3,000, which is amazing. We've got 48 sites, uh, I'm running across England, Scotland, Wales, and Northern Ireland, all ages, 6 and upwards. And we're collating all the baseline data at the moment. So looking at how these aspects all compare to individuals at one time point, we need to wait for 24 months of follow-up before we can look at how things impact on flare. So I can't tell you that yet, but we will hopefully have the baseline data set analyzed by the end of this year. So I'll be able to come back and give you some, some early insights about that pretty soon.

That would be awesome. Yeah, no, I— there must be some research out there because, well, I've done uBiome samples a couple of times and they always give you some correlation of your microbiome towards people with a certain disease. And I always score super high on the, on the IBD scales, which I don't have, which doesn't make me terribly happy, but somehow I've escaped the symptoms or any, you know, sign of the disease.

Yeah. And again, that just goes to show you how little we know about the area as well. So we know that if you look at people with Crohn's disease and ulcerative colitis versus healthy controls and compared to each other, there's massive variation. And, you know, there is a— there is an observable dysbiosis in people with Crohn's disease and ulcerative colitis compared to healthy controls. We know that the diversity of the gut microbiome is less So there are less species, there's less genes in the microbiome in people with inflammatory bowel disease compared to people without. And we can start to see some, some trends that emerge consistently amongst the datasets in terms of different species or groups of bugs that are downregulated or upregulated in others. But beyond that, we're still trying to pick this. There is a massive issue of causality, that observable dysbiosis, how much of it causes the disease to develop in the first place and how much of it is the consequence or the effect of the inflammation or the treatment that we're giving and or the, the alteration in an individual's lifestyle or diet, as I mentioned earlier, if they have developed Crohn's disease or ulcerative colitis over time. So very large groups of people followed prior to the development of disease and then afterwards longitudinally. To me, that's the way that we get at this. It's not simple and it's not particularly cheap, but, but with sufficient resource, we can start to really tackle this in detail.

And are there any probiotics that are currently recommended for IBD?

Short answer is no. There was quite a lot of interest around this a number of years ago. To my mind, the promise has not lived up with the data that we're seeing. So the data for probiotics in ulcerative colitis and Crohn's disease is unfortunately— it's very disappointing. And so where people, where patients come to me and say they're taking a probiotic or ask if they can take one, I say sure, I think it's unlikely to do any harm, but I don't prescribe them routinely in my practice. I don't. And it's similar with antibiotics. Therapy too. There are some very specific areas where you might, but as a whole, I think unfortunately the answer is no at the moment.

Yeah, because I know there was that— what is that— VSL-3 that was a super high dose one that I know was used for some gut issues, but I'm not sure which ones. Was that the one that was, was sort of looked at as a potential hope?

Yeah, VSL-3, and we used it quite a lot for a period of time. There's a lot of hope that it might help pouchitis. This is where individuals with ulcerative colitis had the colon removed and they've had their ileostomy, their stoma reversed, and an artificial rectum made out of a J-loop of small bowel that's then plumbed right back in to the anal canal in the normal way. That has a propensity to get inflamed. That so-called pouch gets inflamed. So again, we add the word -itis to anything to make it inflamed and make ourselves sound clever. So that's pouchitis. And there was good data that that the VSL-3 worked in that situation. But my experience and many others in clinical practice is that actually the effects were relatively low. And thankfully, this is one of the areas where some of the newer drugs that we're seeing— us can— perhaps particularly vedolizumab, Entyvio— in this, in this cohort of patients looks to be pretty effective in helping treat this condition.

Okay, well Was there anything that I should have asked that I haven't yet?

Well, Lindsey Parsons, you've asked some great questions. Well, I could talk about diet and microbiome and the gut in health and disease and particularly Crohn's disease and ulcerative colitis all night long, but I think, I think we've covered most aspects. I think what I would want to say is that we don't know what causes these diseases for an individual. Eating junk food is not the cause of developing Crohn's disease or ulcerative colitis. It's much more complex and nuanced monster than that. There are plenty of people who are unfortunate enough to develop these conditions having done absolutely nothing wrong, eating very, very healthily, and it's the bad luck of their genes and, and their exposed environment and their microbiome over time. We are— I'm always amazed by just how profound the impact of these conditions can be for an individual, their family, and the way it can affect their lives. I've looked after many thousands of people over the last decade, and really the effect can be very, very devastating. Thankfully, now with earlier diagnosis and earlier, more aggressive treatment with some of our newer drugs, we are able for a large number of people to control the conditions almost completely. If not with the first type of drug that we use for a person, with a second or perhaps a third go, we get it right. We get them well and keep them well. But unfortunately for too many people, there is a big unmet need. And I think mine and many others' hopes is that in addition to newer drug therapies that are coming out, that further understanding the role of diet, lifestyle, and the microbiome will enable us to layer in additional therapeutic slants by giving people a personalized dietary strategy, by maybe giving them a microbiome manipulation on top of the regular medication. And then doing this by also deploying novel digital health solutions like the offering from Washi Health, um, also from some of the other offerings that are out there that enable people to track and deal with not just the symptom loads, the inflammation throughout home tracking, but also the psychosocial burden so that we can help care for the whole patient and hopefully keep people as close to a normal quality of life as possible for the duration of the disease. Ultimately, our efforts are moving towards trying to find a cure and trying to find the true cause so that we can intervene to prevent the diseases from developing in the first place. And that's going to keep me and many others busy for at least another decade or two. But it's, you know, it's a big piece of work because these conditions are, are global now. They are of global pandemic proportions, and we need to invest as much time, effort, money into tackling this as we possibly can.

Well, I, I, I'm reminded of another study that was on the AIP diet, autoimmune protocol diet for Hashimoto's. And one of the biggest challenges when you're talking about finding diets that help people, you know, help, help disease conditions, you know, at least symptoms quiet and potentially reverse, is that people don't stick well to diets that aren't, you know, the what everybody else is eating. And in this, in this one study, they used health coaches to— which is what I do, I'm a health coach— to keep people on the diet and to encourage them and support them. And I'm wondering if that might be a component of a future study.

Yeah, for sure. For sure, Lindsey Parsons. This is critical. I mean, there are really simple things. In Scotland, where I work, a lot of people eat very, very well. There's a lot of people who don't eat particularly well and have never been taught how to cook. So for me to say to someone in clinic, don't eat processed food, cook from fresh, is all very well and good. But there is, there is a very simple educational need that's required there. So that's the one side. And then the second side is how do you then implement these changes at scale? You know, we can look at the history of smoking. We knew what caused lung cancer for many years. How long did it take? How much effort did it require to stop people smoking? The same with obesity and type 2 diabetes, where we know the driver is, you know, overconsumption of highly calorific foods. And can we get people to, to address these issues at scale across the globe against some of the major pressures from the food industry, which we have to try and tackle in a much more aggressive manner, I think, at an institutional and governmental level. These are, these are some of the big challenges that we need to tackle head on, but absolutely, Interventions with health coaches that can help deploy these strategies at the individual as well as the population-based level, I think, are going to be really integral. But we should test them as well. We should test them as part of the strategies. We should, we should see randomized control evidence to support all of these different approaches so we can then see where governments and health societies, boards, can invest the money to make the biggest improvements across the piece.

Right. No, it'd be great to have the research supporting it because then maybe that would start to be covered by insurance, which would definitely remove the barrier for most people to getting that kind coaching.

Yeah, yeah, for sure, for sure.

Okay, well, thank you so much for coming on and for sharing about your studies and all of your knowledge on this topic. This was awesome.

Oh, my pleasure, Lindsey. And if people want to find out more information, perhaps you can, you can share in the show notes the links to—

yes, all of the links to the study and to your Twitter.

People can find us on— find me on social and hit me up with any questions that they might want to have. And if they're interested, I mean, signing up for the studies and getting further information, all the links will be there.

Oh, okay.

Great. Great. I will, I will be sure to put those all in.

Well, thank you so much.

Awesome. Thank you, Lindsey. Great to speak to you.

You too. I love interviewing the British. They feel so much more articulate than Americans.

Anyway, great show.

So if you have any questions about my interviews or gut health or suggestions for guests, please feel free to write me at lindsey@highdeserthealthcoaching.com. And be sure to include whether I can read your letter on the air. I'd love hearing from my listeners. Also, don't forget about supporting the show through my affiliations by going to highdeserthealthcoaching.com and choosing supplements and lab tests. Or if you've heard about something on my show, be sure to go through the links in the show notes or on my website so that I get credit for it. On my supplements and lab tests area, I have a full script dispensary, which is Basically an online drugstore where you can get access to practitioner-grade supplements that have passed strong quality controls, many of which are not sold on the open market. So please go and support the show that way. And thank you for listening. And here's wishing you all the perfect stool.