Dr Lacy hosts Dr Andrea Shin to discuss the changes in criteria from Rome IV to Rome V for bowel disorders of gut-brain interaction, including IBS, chronic constipation, and chronic diarrhea.

Brian Lacy, MD, PhD, is a professor of medicine at Mayo Clinic-Florida in Jacksonville, Florida. Andrea Shin, MD, is an associate professor of medicine at the Vatche and Tamar Manoukian Division of Digestive Diseases at University of California Los Angeles.

Rome V Bowel Disorders: Diagnostic and Treatment Takeaways

• Rome V defines 6 bowel disorder categories. For irritable bowel syndrome (IBS), it includes abdominal pain or discomfort associated with bowel habits on at least 3 days per month, compared with Rome IV’s threshold of at least 1 day per week.
• IBS treatment depends on the most bothersome symptoms. Dr. Shin described lifestyle measures followed by therapies targeting constipation, diarrhea, or persistent pain; options vary by IBS subtype.
• Chronic constipation and functional diarrhea differ from their IBS counterparts chiefly because pain or discomfort is not a predominant feature. For longstanding constipation without alarm features or sudden bowel habit changes, colonoscopy is not always indicated.

Dr Lacy:

Welcome to Gut Check, a podcast from the Gastroenterology Learning Network. My name is Brian Lacey. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and I am absolutely delighted to be speaking today with Dr. Andrea Shin, associate professor of medicine at UCLA in Los Angeles. Our podcast today focuses on one of the key content areas of the recently released Rome V criteria for disorders of gut-brain interaction, that being bowel disorders. And who better to have on the podcast today than Dr. Shin, one of the lead authors of the revised Rome V criteria.

So Dr. Shin, welcome. Let's start simply by setting the stage for our listeners. What are disorders of gut-brain interaction, something we commonly refer to as a DGBI?

Dr Shin:

Great question. DGBI, these refer to chronic gut symptoms. So these are symptoms like bloating, pain, diarrhea, constipation, nausea. These are real symptoms, recurrent physiological symptoms that aren't due to any structural damage to the digestive tract, but related to alterations in how the digestive system is functioning and communicating with the central nervous system.

Dr Lacy:

The Rome V criteria released in May of this year for bowel disorders now includes 6 major categories. What are those categories?

Dr Shin:

Right. So the Rome V defined 6 categories based on key clinical features, and the 6 categories that are included in this iteration of ROME include irritable bowel syndrome or IBS, chronic constipation, functional diarrhea, functional abdominal bloating, unclassified bowel disorders, and opioid-induced constipation.

Dr Lacy:

Great. Let's kind of tackle these in turn, and let's focus on one of the most common disorders of gut-brain interaction, that of IBS or irritable bowel syndrome. And new data will show that this has a prevalence of about 9% worldwide, meaning one in 11 adults meet criteria for IBS. So how is IBS defined and what are the key differences in the definition for IBS using Rome V compared to Rome IV?

Dr Shin:

So IBS is defined based on the presence of recurrent abdominal pain or discomfort that occurs at least 3 days per month. And there is an association with bowel functions or bowel habits. And the relationship between the pain or discomfort with bowel dysfunction or bowel habits means that either the pain or discomfort is related to bowel movements or the frequency of bowel movements or the appearance and form of the actual stool. And with IBS, people will typically report at least 2 of the following abnormalities related to their bowel functions in relationship to the pain or discomfort. There's a chronic nature to this. So these aren't symptoms that have just been present for a week, but they've been present for months and there is a relapsing remitting nature. So they're not always at the same level of severity constantly, consistently throughout the week or throughout the month.

Now, the main difference between Rome V and Rome IV were based on 2 minor changes. So Rome V reintroduced the word discomfort into the criteria. Previously, Rome defined IBS based on the presence of pain and abnormal bowel habits. The reason the word discomfort was introduced was after going back and reviewing data across the globe, it was recognized that not all countries and cultures and languages necessarily report pain the same way. And in some cultures, some languages, when we rely specifically on a narrow definition of pain, we probably weren't capturing everyone who actually had IBS. And so the word discomfort was reintroduced for that reason. The other change that was made was the frequency of symptoms. So like I mentioned with Rome V, we identify IBS based on symptoms that are present at least 3 days per month. Rome IV had a stricter definition where people needed to report the presence of symptoms at least one day per week.

And looking at population-level data, it was recognized that when you apply such a strict definition that we're really capturing a more severe subset of people with IBS. And there can be people who have milder symptoms that still have the same pattern, probably still have the same underlying processes that are driving the symptoms, but just aren't as severe. And so being more inclusive in the definition to be able to acknowledge that there are milder forms of IBS, that was the reason for changing the frequency threshold.

Dr Lacy:

So amazing number of teaching points. I'm going to highlight just two. One is that people report pain differently and there's a spectrum of pain and discomfort. So incorporating that word back in the definition seems really important. And also pain and discomfort doesn't have to be present every day. It's just 3 days per month, as you mentioned, to meet strict Rome V criteria.

So when you're seeing somebody in the office and they ask, Dr. Shin, why do I have these symptoms? What do you tell them about why IBS occurs? Is it genetic in nature? Is it due to some prior infection?

Dr Shin:

That's a question that comes up in the clinic a lot and I completely understand because people want to understand the disorder, be educated and recognize what are things that they can do. IBS is what we refer to as a multifactorial disorder, so it's very complex. And this generally means that there are multiple processes, risk factors, variables, insults along the way that probably accumulate and collectively contribute to the development of IBS. Genetics can definitely be a part of it. There is a relationship between hereditary risk and your likelihood of having IBS, but that's almost always not the sole cause. There are other factors as well—early life stress, physical stress, emotional stressors, even a history of infection. All of these can contribute to trigger dysfunction within the gut and across the gut brain axis, and that presents as IBS or the symptoms that we talked about earlier.

Dr Lacy:

Wonderful. Thank you. In a nutshell, could you give us your personal algorithm for treating somebody with IBS and constipation?

Dr Shin:

Yeah, obviously the algorithms can vary from person to person, but in general, we first start by making sure people are properly educated on appropriate lifestyle and behavior that can be important in managing symptoms. This can relate to things like sleep schedules, regular physical exercise, fluid intake, fiber intake and diet. But obviously we want to then move on to what sorts of treatments we can include in addition to lifestyle and behavior. For someone who has IBS with constipation, I'll usually start by trying to identify how bothersome the symptoms are in relationship to one another. So as we mentioned before, with IBS, we're talking about both pain or discomfort and bowel dysfunction. So with constipation, the bowel dysfunction is constipation. But if the pain or discomfort is relatively mild in relationship to the constipation, we might start by focusing our treatment on first-line laxative therapies like osmotic laxative simply to address bowel habits.

For someone who has more of moderate or more severe symptoms and are noticeably bothered by both the pain and the constipation, we probably in that case move on to licensed IBS-C therapies. There are a number of different prescription therapies that are available now. This includes the category of agents that we refer to as secretagogues, linaclotide, plecanatide, lubiprostone. These are all medications that increase fluid and electrolyte secretion in the digestive or in the gastrointestinal lumen. And then there are medications like tenapanor that prevent or inhibit salt and water absorption, and these have all been tested in IBS-C, and so these are prescription therapies that we'll commonly offer.

Now, if somebody has their constipation adequately managed, but the pain continues to be an issue, this is where we might incorporate the use of gut-brain neuromodulators like tricyclic antidepressants or tricyclic agents, serotonin, norepinephrine reuptake inhibitors. These are a different class of medication and there are different categories, but they're very helpful because they can target the pathways that are involved in regulating or modulating pain signals.

Dr Lacy:

Wow. So much information buried in there. So if you're listening to this, you might want to put it on pause, rewind just a little bit and listen to it again because there's so much great information. But what I really want to take from this is one, one size does not fit all, and so you have to personalize treatment, as you said, really figure out what's bothersome to the patient. And number two, there are a lot of treatment options available, so don't give up if you don't respond well to one agent.

So similarly, but kind of shifting gears a little bit, what's the Dr. Shin personalized algorithm for treating somebody with IBS and diarrhea? Yeah,

Dr Shin:

Different subtypes require different approaches. Conceptually, we still start with this similar mindset of discussing diet, environmental factors, lifestyles, things that they can control in their day-to-day life that might be contributing to symptoms, making sure that everyone is properly informed. But specific treatments for IBS with diarrhea, this can include a number of prescription agents as well. So for diarrhea, first line straightforward medications may include loperamide. This is actually available over the counter, very inexpensive, but it works by decreasing transit or how quickly things move through the digestive tract and it can increase fluid absorption. So it can actually help treat symptoms like urgency or stool frequency, which are oftentimes very problematic symptoms for people who have IBS with diarrhea. There are several prescription therapies available as well.

So many may have heard of a nonabsorbable antibiotic known as rifaximin. This is approved for treatment of IBS with diarrhea, so this can be a prescription agent that can be offered for people. It is a short course. It's not meant to be a long-term treatment, so it's a 14-day treatment. But if it's helpful and treatment is required again in the future, it can be repeated. Then there are prescription agents such as a medication known as eluxadoline. This is a medication that works on, it's what they call a mixed opioid agonist-antagonist. So it acts on various receptors throughout the GI tract, and it's been studied in clinical trials and shown to improve both pain and diarrhea. One important note is that people who have had a history of their gallbladder being removed, a history of pancreatitis, or who have a history of frequent alcohol intake, these people should not be taking eluxadoline because some of the studies show there's a very rare risk of pancreatitis in those individuals.

And then another category of prescription agents that we can sometimes reach for, not necessarily licensed specifically for IBS-D, but helpful for diarrhea, are agents such as bile acid binders.

And these include medications like colestipol, cholestyramine, colesevelam. They work by helping to sequester or lock up bile acids that can be excreted in higher levels in some people who have diarrhea and can help reduce the laxative or irritating effects of bile acids in the digestive tract. So these are different categories of prescription agents.

I will also say that there are structured dietary interventions that we'll sometimes use as well, especially if somebody has food-related symptoms or a lot of food-related discomfort. The low FODMAP diet, many people have heard of that. This is a diet that reduces the intake of certain fermentable carbohydrates, and they can be helpful for alleviating some of the symptoms of IBS. And interestingly, even though you can use it across different IBS subtypes, the low FODMAP diet has been more often studied in people who have had IBS with diarrhea or mixed symptoms.

Dr Lacy:

Well, Andrea, thank you for such a comprehensive overview in a limited amount of time. That's just great. So let's shift gears a little bit to another very common bowel disorder, another common disorder of gut-brain interaction, that being chronic constipation. Really common worldwide prevalence of 14%, meaning 1 in 7 adults meet criteria for chronic constipation. So what's the difference in diagnosing chronic constipation from IBS with constipation? Is there a big difference? Are these really two very different disorders or do you think they exist on a spectrum?

Dr Shin:

I think the key takeaway from this is recognizing that the distinction for a clinical diagnosis is really related to the presence of pain or discomfort. Chronic constipation does share a lot with IBS with constipation-predominant features, but in chronic constipation, the pain and discomfort that is classical in IBS is not a prevailing feature, but they do definitely occur on a spectrum. And actually some studies have showed that people can move from one category to another over time, and I think that this is a concept that the medical and scientific community have widely embraced. So yes, we do define them differently based on key symptoms, but we recognize symptoms do change over time, and it's more accurately described as a continuum or a spectrum rather than two fixed categories of different underlying dysfunction.

Dr Lacy:

Wonderful. So one question that comes up a lot from both patients and providers is the role of colonoscopy in somebody with chronic constipation who may be struggling with their symptoms. And is there good data to support colonoscopy in all these patients or we should focus on a specific subset or is there a good data to say, no, we should not be doing colonoscopy in these patients?

Dr Shin:

Yeah, this is such a great question because it comes up a lot, and arguably colonoscopy is one of the tools that has allowed gastroenterologists to make the biggest impact on public health in terms of colon cancer screening and other diagnostic areas. But the interesting thing about chronic constipation is that the yield of a diagnostic colonoscopy in someone who has had long-standing symptoms of constipation is actually relatively low. And if you have someone who doesn't have what we call those classical alarm features or someone who's not presenting with sudden or acute changes in their bowel habits, a colonoscopy is not always indicated. And actually we have some studies to show that applying this positive clinical approach and reducing testing burden is actually associated with similar outcomes and no difference in the number of alternative or structural diseases that are diagnosed later on down the road. So I think that's really reassuring.

The other data point that I'd like to point out is that we often want to offer colonoscopy as even just a level of reassurance, and we feel at least we're helping in that manner, but there have been studies that actually show that the testing itself doesn't actually provide the reassurance that we're helping. In fact, there was a study that demonstrated that a negative colonoscopy not only didn't provide additional reassurance, it didn't lead to any measurable improvements in quality of life. And so I think this is information that as clinicians, we really have to be aware of and be able to counsel our patients appropriately.

Dr Lacy:

Yeah, great teaching points. Repeated testing can be expensive and it carries some risks and it may not reassure patients. It actually may sometimes just tells patients, maybe we're not sure what we're doing.

Let's shift gears again. So functional diarrhea, chronic diarrhea remains poorly understood. How do the Rome V guidelines define functional diarrhea?

Dr Shin:

So functional diarrhea is really defined by the presence of loose or watery stools in the absence of an alternative condition like an infection, inflammatory bowel disease, celiac disease, and so forth. Like chronic constipation in IBS-C, functional diarrhea shares a lot with IBS-D and probably exists on a spectrum, but the distinction is that there is not a predominant pain component in functional diarrhea.

Dr Lacy:

So the teaching point, the presence of abdominal pain or discomfort kind of distinguishes the two, and I like your analogy that they probably do exist on a spectrum. How about treatments? Do the treatments exist on a spectrum too — you gave us this great description about treatments for IBS with diarrhea, is it kind of the same list of possible agents?

Dr Shin:

It's actually the same list. Most of what we use to treat functional diarrhea is heavily extrapolated from the treatments we have available for IBS-D. There haven't really been as many or really relatively few clinical trials that have tested drugs specifically for functional diarrhea, but things that work for IBS with diarrhea can generally be applied to functional diarrhea as well.

Dr Lacy:

I want to cover 2 more big topics here because this is just great, such a wealth of information. Bloating and distension are common symptoms. In fact, in the United States, 14 to 18% of US adults report symptoms of gas and bloating on a weekly basis. So how is functional abdominal bloating, the third major bowel disorder category, how is this defined and what are some treatments?

Dr Shin:

So functional abdominal bloating is defined as the presence of recurrent bloating or visible distension that occurs at least once per week. In this condition, people are not reporting the same clinical features that would qualify them for IBS or other overlapping disorders of gut-brain interaction. That being said, bloating is a really common symptom in IBS. So acknowledging, again, what are their most bothersome symptoms can help us more accurately define what definition best describes their picture. And then the next part of that question was treatment. So functional abdominal bloating, very challenging to treat actually. As of yet, there's no prescription therapy where the prescription is primarily indicated for bloating. And typically bloating has been studied in the context of another disorder like IBS or chronic constipation. Fortunately, many of the licensed therapies for IBS have been analyzed in terms of their effects on bloating symptoms, and the data is actually pretty helpful because it's been shown that these treatments that were tested in terms of their effect on symptoms such as pain and bowel habits also have an impact on bloating symptoms.

So I'll usually explain that to patients if we're thinking about starting a licensed or a prescription therapy for their IBS symptoms, that over time this can help improve their bloating symptoms as well. The other treatment that's nonprescription-based that has been tested in people who struggle with recurrent abdominal bloating or distension is actually a non-pharmacological treatment known as thoracoabdominal wall guided biofeedback. So this is targeting a mechanism called abdominophrenic dyssynergia, which has been extensively studied by a few groups, and it's been shown that impairment in this reflex called the viscerosomatic reflex can actually lead to altered gas handling. And this can be targeted through a very intentional kind of body-based program, diaphragmatic breathing, biofeedback, and sometimes you can combine these approaches together.

Dr Lacy:

Wonderful. As we wind down, opioid-induced constipation is included in the bowel disorders guideline, and you made a point in your very nice article published in Gastroenterology in May of this year that this is different than other bowel disorders because this is a result of a medication side effect. So how common is opioid-induced constipation?

Dr Shin:

So opioid-induced constipation is a debilitating condition, and the Rome Foundation performs some epidemiologic surveys that estimated the prevalence or the frequency of opioid-induced constipation, ranging from 1 to 2%, but depending on what region of the world we're looking at. It is, as you pointed out, a disorder that is caused by a medication, but it's included in the Rome V bowel disorders because it presents with a lot of the same symptom-based features and exists on a clinical continuum, even though it does have an identifiable cause. But what the opioids are doing is they're affecting the neuroenteric system at multiple levels. There is an impact on gut-brain functions, enteric mechanisms. We recognize that this is due to the medication, but it is in a way dysregulating the gut-brain axis. And in addition to that, opioid-induced constipation can actually unmask or even worsen a pre-existing DGBI. So we felt it was really important to include this category to give people guidance in terms of how to recognize it and how to treat it.

Dr Lacy:

Such a nice description about OIC. So Andrea, this has really been a great discussion overall. Thank you so very much. Any last comments for our listeners?

Dr Shin:

I think our final comment is we're really excited that Rome V has been shared with the general public and with the medical community. Biggest takeaways are this is a diagnosis that we can make clinically as clinicians, and getting education and information out early and recognizing that there are many different treatment options available, I think should be very encouraging and keep us optimistic looking forward.

Dr Lacy:

Wonderful. Dr. Shin, again, thank you so very much for lending your expertise on this important topic. 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. Andrea Shin, Associate Professor of Medicine at UCLA in Los Angeles. I'm sure 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.