Gut Check: Drs Brian Lacy and Ami Sperber Delve Into DGBI

Brian Lacy, MD, is a professor of medicine at Mayo Clinic-Jacksonville in Florida. Ami Sperber, MD, is  emeritus professor of medicine at Ben-Gurion University of the Negev, Be'er Sheva, Israel.

In this episode of Gut Check, host Brian Lacy, MD, talks with Dr Ami Sperber about how disorders of gut-brain interaction can overlap, and how this can change treatment paradigms.

TRANSCRIPT:

Welcome to Gut Check, a podcast from the Gastroenterology Learning Network. We are recording live today from Washington, DC during DDW, Digestive Disease Week, a large international conference that focuses on all types of gastrointestinal disorders. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and I am absolutely delighted to be speaking today with Dr. Ami Sperber, who is Emeritus Professor of Medicine at Ben Gurion University in Israel. Dr. Sperber is a nationally recognized expert in disorders of gut-brain interaction, which were previously called functional bowel disorders.

He has authored countless articles and guidelines on the evaluation, diagnosis, and treatment of disorders of gut-brain interaction, which we will both frequently refer to today as DGBI. He is a sought-after lecturer nationally and internationally on all topics related to DGBI disorders of gut -brain interaction. Today, we're going to focus on the topic of the overlap of DGBI and why this is important to the clinician and to the patient.

So Dr. Sperber, welcome. What a delight to have you here. Let's set the stage for some of our listeners who may not be as familiar with DGBI, disorders of gut-brain interaction, as you are. What exactly are DGBI?

Dr Sperber: Well, first of all, thank you for having me. It's an honor. If you look back, starting with what you said earlier, that these were formally functional gastrointestinal disorders, and in a way that was separating structural diseases from functional diseases. One is the way it's built, and the other is the way it functions. That sort of set up a dichotomy where people had a true organic disease, let's say like inflammatory bowel disease, or they have this like phony thing, a functional bowel disorder.

And one of the things we tried to get at by changing it to disorders of gut-brain, or DGBI, is to look much further into the mechanisms that lead to the suffering of the people who have these disorders. And probably the main thing is bidirectional communication between the gut itself and the brain through the central nervous system. We've learned that that is critical in terms of set points with sensitivity and all sorts of other factors.

Dr Lacy: Yeah, and I like that phrase an awful lot and something we can all use with our patients that's bidirectional highway, that bidirectional pathway between the brain and the gut. And I think that makes sense to a lot of our patients. So Ami, how common are DGBI in general and more specifically, what are some of the most common disorders of gut-brain interaction?

Dr Sperber: So, we recently finished conducting a global study which included 54,000 participants from 26 countries and we found really to our surprise that 40, slightly more than 40% of the participants met diagnostic criteria for at least one DGBI— there are 22 of them. So it's not as if they're all the same. But those people were certainly affected by it. It wasn't just by chance that they met the diagnostic criteria. And that's an astoundingly high number, in my opinion.

Dr Lacy: So you've already kind of answered my next question. As usual, you're always one step ahead of me. And the question was going to be, why is this topic so important? And it's because this is incredibly prevalent, 40% of the population. So thinking about this topic of overlap and disorders of gut-brain interaction, does knowing that there overlap exists, does it change the natural history of patients with these disorders? Does this overlap diagnosis possibly change the treatment paradigm? What does it do in terms of health care costs?

Dr Sperber: I think we have to be aware of the fact that if people have more than one disorder—and we'll go into the various types of disorders soon—then that makes their clinical picture, let's call it, a lot more severe. There's a higher degree of psychosocial involvement, anxiety, depression, somatization, which means expressing emotions through the body, basically, and having systems in different organ systems, which are also not identifiable in terms of the tests that we know how to do. But it definitely leads to a person suffering a lot more than someone that does not have this overlap. And I would add, I'm not sure overlap's a great term, actually. We use it. Perhaps better would be coexisting or concomitant, but we'll stay with overlap because that's what everybody does.

Dr Lacy: All right I like that point and maybe we should be changing over vocabulary and it was he as we go through this discussion think about overlap or concomitant disorders or coexisting I like that too, and I've been intentionally vague about the word overlap. But when we think about the overlap of DGBI disorders of gut -brain interaction, does that refer just to the overlap of one DGBI with another, such as the overlap of IBS with functional dyspepsia, or are there other types of overlap or coexisting disorders?

Dr Sperber: So when I try to organize my thoughts around this and make sure I have a pretty clear picture in my mind, I classify this into three different groups. The first group would be DGBI with nongastrointestinal disorders, that could include, I mean, it's a whole wealth of things, fibromyalgia, chronic sleep disorder, pelvic pain, you name it, there are at least 15 or 20 of these disorders that also do not have identifiable diagnostic tests in order to diagnose them, but they very much affect the patient's experience, and when they have them together with the DGBI, it just compounds the problem.

The second classification would be DGBI with another gastrointestinal disorder, but not a DGBI, and the 2 major examples of that are inflammatory bowel disease— Crohn's disease and colitis—and celiac disease. The third one is what you alluded to earlier, which is a combination or a coexistence of more than one DGBI. To understand that, we divide the gastrointestinal tract, the digestive tract, into 4 regions. One is the esophagus. The second is the stomach and the beginning of the small bowel or gastroduodenum. The third is the bowel itself, usually the large intestine, and the fourth is the anorectal area.

And when we talk about overlap among the DGBI, we're saying that somebody might have, for example — I think you mentioned this, IBS and functional dyspepsia, for example. But if you think about the fact that there are 4 regions and 22 DGBI, and they could have 2 overlaps, 3 overlaps, or 4 overlaps even, and this is a large body of issues.

Dr Lacy: Wonderful, so I like the way you classify that into kind of these three big categories of overlapping or coexisting disorders. So let's tackle the overlap of DGBI with nongastrointestinal disorders. And you mentioned fibromyalgia and dyspareunia and maybe TMJ syndrome. How common is this overlap?

Dr Sperber: Quite common—I think much more common than most people would think. We ourselves did a study on—we did actually parallel studies where we looked at fibromyalgia in IBS patients and IBS in fibromyalgia patients, and we found that the prevalence of having both was about 30% or 32%, which is very high, but it's usually not diagnosed in clinical practice. And one of the things that fascinates me is how does someone that have both become an IBS patient or a fibromyalgia patient? Is it just because they got off on the third floor and there was a gastroenterology clinic there, or because that bothers them more or whatever? But the doctors in each subspecialty—really, I don't want to say everyone because that's not right—but I really don't think about this issue of coexistence, which has a very strong effect. So that was the first part.

Second part, we looked at the coexistence in terms of psychological issues like anxiety, depression, somatization. We looked at quality of life. We looked at sense of coherence, which is a scale to evaluate how someone copes with what they have and others. And we found, we actually did some gradations. I don't wanna go into great detail, but for example, in the patients with IBS, we divided into those that go to doctors and those that don't go to doctors. And then we had a control group of those that don't have it. And we found incremental changes in all of these factors so that those that had IBS and go to a doctor had much more severe symptoms, and the second group was those who have it don't go under control. And then the next thing we did was to look at people that had IBS only, IBS and fibromyalgia, and not at all. And once again, we found that those that have IBS and fibromyalgia have much more severe disease than all those.

Now, once again, if this is not recognized by the treating doctor, then we're losing an opportunity to communicate with the patients, to develop together with them a treatment plan, and make it relevant to their combination of problems.

Dr Lacy: So some wonderful teaching and educational points there. One is that there's a difference between consulters and nonconsulters, those who seek out the advice of a healthcare provider. But I also really liked—and you may have heard me laugh—that if you get off on the sixth floor and you see a rheumatologist, they're going to focus on your fibromyalgia symptoms, but the third floor may be more on your IBS symptoms. So that's really fascinating how we think about this.

And when we do think about this overlap of DGBIs and nongastrointestinal disorders, does that mean that there's a similar pathophysiologic process involved in both sets of disorders such as fibromyalgia and IBS and how might this type of overlap affect the diagnostic workup and treatment?

Dr Sperber: Well the bottom line is we don't really know but we do have a lot of thoughts about this and one of the ideas that's been promoted is what's called the central sensitivity syndrome, which means that all of these things may be manifested in different body systems— fibromyalgia, the muscles and the bones; IBS, the intestine; and so on and so forth. But they all relate to, if you think back to what I talked about, the brain-gut axis. There's also a somatic axis of the muscles and the bones and the central nervous system. And if the set point for whatever it is, pain or any other symptom, if something's gone wrong with the set point, then people become much more sensitive and that could be common to all of these various disorders.

So that's one of the things that they're looking at. Just to emphasize, it's really two different types of problem in a way because IBS is what we call visceral, meaning it belongs to the internal organs, whereas all the others are somatic, meaning that they're outside of that.

Dr Lacy:But I like this whole concept and for our listeners, this concept of central sensitization syndrome, where we recognize these patients are more sensitive than usual. So Ami, this is great. So let's shift gears now and think about the overlap of DGBI with other gastrointestinal disorders, and maybe inflammatory bowel disease is a good one to think about. How common is that overlap?

Dr Sperber: We're talking about people that have a quiescent disease like Crohn's or colitis. There are different ways of defining that. Most profound ways to do endoscopy and see that there's no inflammation or disease activity, as we call it. But these are people who feel okay, and yet they still have symptoms which we would then call IBS-like symptoms. Some people said ILS, there are different ways of approaching this. One of the real problems here is how do you interpret those symptoms? Because particularly specialists in inflammatory bowel disease will often think that this is an exacerbation of the colitis. And then they'll do more testing and they'll do more treatment and it's really sort of out of line because it's not actually responding to the issue that's the active one, which is that they have DGBI symptoms and not inflammatory symptoms. So you lose time both in doing extra tests and money, of course, and then, you know, you might add steroids, which is really not so great if you're treating IBS symptoms. So awareness is very.. and then we do have treatments for the GBI. So we're kind of losing out in several directions at the same time.

Dr Lacy:  And I like a critical point you made there, that this is not the patient with an active flare of Crohn's disease with fecal calprotectin of 1000 levels and CRP levels. Hi, these are quiescent patients where you think you've got their IBD under good control, but they're having persistent symptoms that may reflect visceral hypersensitivity. And so when you think about that, does that change how you might then treat these patients? You said, you know, avoiding steroids, but what might you do in that clinical scenario?

Dr Sperber: So we have a graded approach to treating irritable bowel syndrome or other DGBI. And this includes dietary education, it could include change in lifestyle, include various medications of different levels of effect, including going up to what we call neuromodulators or what was called antidepressants in the past, but we call them neuromodulators because they work on the communication between the brain and the gut. And we have a whole slew now of behavioral treatments, including cognitive behavioral therapy, hypnosis, and many others. So definitely if you're aware of what's going on, you have an excellent toolbox of treatments that you can tailor to the patient. And the other thing I would emphasize is that that's a partnership. It's not you deciding what the patient should get and then they're treated, but you explaining the various options the benefits, potential problems with it and deciding together what to do.

Dr Lacy: Yeah, so another great teaching point from this clinician, Dr. Sperber, with just probably 60 years of experience—communication is key. So, Ami, let's discuss the overlap of one DGBI with another. And we briefly mentioned earlier the overlap of IBS with functional dyspepsia. How common is that and how common is the overlap of one DGBI with another?

Dr Sperber: First of all, we divide the gastrointestinal tract into 4: the esophageal disorders, the gastroduodenal disorders, the bowel disorders, and the anorectal disorders. And we define coexisting disorders if you have 1 or 2, well, not 1—2 or 3 of these areas or regions involved. So if you have, for example, 2 esophageal disorders, we wouldn't consider that to be overlap, because it's in the same region. But if you have an esophageal, let's say, functional dysphagia, meaning you have problems swallowing and the tests don't show anything wrong, together with functional dyspepsia, then you do have an overlap of 2. And theoretically, you could have 2, 3, or 4 regions involved, because if it's only 1 region, we wouldn't call it an overlap, obviously.

And what we've seen, we found that about, once again, going back to this large study that I mentioned before, as I said, about 40% have 1 region. But among those, about 25% have 2 regions, and about 7% have 3 regions, and about 2% have 4 regions. So these people that really have a lot of regions of the gastrointestinal tract involved. And what we found is you see an incremental increase together with the number of regions involved in terms of psychological variables, in terms of quality of life, in terms of use of medication, in terms of going to doctors. There's a whole slew of indices that we could use that show that the more regions that are involved, the worse the situation is in terms of the patient.

One of the major problems is, and there was a study, I was not involved in that, but there was a study which showed that patients have, let's say, 2, 3, or 4 regions involved, but there's no documentation of that in the medical record. So the doctor either was unaware of that, or did not think it important enough to record. And the treatment reflects that because you need to have a much stronger partnership and maybe treatment strategy with people that have more regions involved than this, just one, although they also obviously need to be treated.

Dr Lacy: So that's a kind of a perfect segue. We know that many health care providers are a little uncomfortable sometimes making the diagnosis of these disorders of gut-brain interaction. So does having an overlap of 2 distinct disorders increase the pretest probability of making a confident diagnosis, or if you have 3 or even 4, should that really help our listeners today making that diagnosis, and do you think there's a level of awareness about that? You kind of already spoke to that.

Dr Sperber: That's actually the main point here because there should be— it should make a difference. And obviously, it's something that doctors should look for and definitely document as well. My experience is that very few think about this at all. They don't even think about — I mean, that may be less subtle than IBS and fibromyalgia because they're both in the digestive tract. But I think doctors are not —everybody has their own subspecialty and their own focus. And they don't really think outside. You know, that's for another doctor. That's not for me to handle. But you're not handling that. You're handling the patient. And to do that, you have to be aware of the whole package, so to speak.

Dr Lacy:  So if you have globus and noncardiac chest pain and functional dyspepsia and functional bloating and IBS constipation, you should feel very confident these are likely DGBIs and move on with treatment. And as we think about that, as we kind of wind down here, if a patient has those multiple overlapping disorders of gut-brain interaction, does that change how you treat these patients?

Dr Sperber: Well, it does in the sense that they would be expected to have more factors involved, things that I mentioned before—anxiety, depression, somatization, medication use, health care utilization, maybe issues at home with the family, with partners—all of these things can be affected by that. And that obviously has to be a focus of treatment. If you just say I'm going to give them medication and I'm not even going to listen to them, then you're totally missing them, and your chance of helping them is negligent.

Dr Lacy: So great teaching point. That patient with multiple overlapping disorders, if you say, "I'm just going to work on the globus and ignore everything else," the likelihood of getting a good treatment response for these global symptoms is pretty small, isn't it? In addition to that, if you're not aware of the fact that that probably is manifested by these other things that I said, then you won't relate to those as well.

Good teaching point. So Ami, we've learned so much here today. Any last thoughts for our listeners?

Dr Sperber: Well, I would just hope that anyone who's listening who's treating patients would become more aware of these coexisting conditions, their significance and ramifications, and relate to it in accordance.

Dr Lacy: Wonderful. So, Ami, again, thank you so very much for being here today.

To our listeners on Apple, Spotify, and other streaming networks, I'm Brian Lacy, a professor of medicine at the Mayo Clinic in Jacksonville, Florida. You have been listening to Gut Check, a podcast from the Gastroenterology Learning Network. And our guest today was Dr. Ami Sperber, emeritus professor from Ben Gurion University of Israel. I hope you found this just as enjoyable as I did. And I look forward to having you join us for future Gut Check podcasts.

Stay well.