Potential Causes of Your Adult Patients’ IBS-D Symptoms
Host: Christina J. Hanson, FNP, South Denver Gastroenterology
Featuring Amy Kassebaum, PA-C, MMS, RD, Northwestern Memorial Hospital
Welcome to Clinical Conversations: Potential Causes of Your Adult Patients’ IBS-D Symptoms.
Christina Hanson and Amy Kassebaum received payment from Salix Pharmaceuticals for their testimonies.
Christina: Hi, I’m Christina Hanson, and thanks for tuning in to Clinical Conversations. Today we’re going to talk about the potential causes of the symptoms of IBS-D, a disorder we see in so many of our patients. We’ll take some time to dive into what might be behind these symptoms, which I think may frame the way you think about the symptoms themselves a little differently.
Irritable bowel syndrome, or IBS, is a common functional bowel disorder that’s associated with several different disordered bowel habits.
The defining feature of IBS is recurring abdominal pain that’s associated with defecation or a change in bowel habits. And IBS is classified into three main subtypes: irritable bowel syndrome with constipation, or IBS-C, irritable bowel syndrome with diarrhea, or IBS-D, and irritable bowel syndrome with mixed symptomology, or IBS-M. Patients with IBS-D experience loose, mushy, or watery stools more than 25% of the time. This equates to Type 6 or 7 on the Bristol Stool Form Scale. These patients may also experience other symptoms like bloating, but these other symptoms aren’t part of the criteria when defining the disorder.
Now that we’ve reviewed the definition and symptoms of IBS-D, let’s dive into what might be causing these symptoms. I’m happy to be joined by Amy Kassebaum, who is a physician assistant and registered dietician from Northwestern Memorial Hospital. Thanks for being here, Amy!
Amy: Thanks, Christina, I’m glad to be here!
Christina: Amy, as I just mentioned, IBS-D can present with a range of symptoms. So, what do we know – what information is out there – about what might be causing these symptoms?
Amy: The pathophysiology of IBS-D is complex, and the exact cause of IBS-D is unknown, but we’re learning more every day.
Many factors are thought to contribute to how symptoms develop in patients with IBS-D. These may include increased permeability in the lining of the GI tract, alterations in gut motility, visceral hypersensitivity, activation of the intestinal immune system, and disturbances in gut-brain function, which is a really interesting area that we’re learning more about.
Christina: There’s also a growing body of evidence that suggests that IBS-D symptoms may be linked to dysbiosis, or changes to the different populations of bacteria that are present in the gut. And we know that bacteria in the gut do play an important role in our health.
Amy: Absolutely. The human gut is inhabited by trillions of microorganisms, including bacteria, which are collectively known as the gut microbiota. Actually, there’s a study that showed that more than 2500 bacterial species reside in the gut. In healthy people, these gut bacteria play an important role in many aspects of health. Studies suggest they help supply nutrients and energy by breaking down dietary components like fiber into molecules called short-chain fatty acids. In addition, they are thought to help support immune development in the GI system; some strains are thought to help defend against pathogens. They may also influence communication between the enteric nervous system and the central nervous system via what is termed the gut-brain axis, which is a two-way communication system that integrates brain and GI functions such as gut motility, appetite, and weight. Studies suggest that bacteria in the gut can also influence the production of serotonin, which plays an important role in intestinal motility, sensation, and secretion. (Based on both in vitro and in vivo studies.)
Christina: I think it’s pretty exciting to also see the increasing body of evidence that suggests that gut dysbiosis may be associated with the development of IBS-D.
In fact, I know of one observational study that showed differences in the gut microbiota in patients with IBS-D compared with healthy subjects. Select differences in the microbiota were associated with IBS symptom severity. The differences that we’re talking about in the microbiota could be differences in the number of unique bacterial species and the balance of these species relative to one another, differences in the overall number of bacteria, and how bacteria are distributed throughout the digestive tract.
Amy: Exactly. And these alterations in the gut microbiome can occur due to common natural and environmental factors. The bacteria in your gut are relatively stable and for the most part resistant to disruptions. But changes in the gut microbiome can still occur due to several factors—for example, a person’s diet or GI infections.
Although we need additional studies to further clarify the role of the gut microbiota in IBS, changes in gut bacteria are thought to be associated with the pathophysiology of IBS-D symptoms in a couple of ways. First, changes in the way bacteria break down nondigestible dietary components can contribute to the accumulation of excessive intestinal gas, which may potentially lead to abdominal pain and bloating. Secondly, increased production of short-chain fatty acids and release of serotonin can be associated with colonic contraction as well as increased motility and transit, and may potentially lead to diarrhea. Finally, activation of the intestinal immune system related to altered gut-immune signaling can result in impaired barrier function and increased intestinal permeability, possibly resulting in abdominal pain and diarrhea. So, there are really a number of ways that changes to bacteria in the gut may be associated with the pathophysiology of IBS-D.
[Based on in vitro and in vivo studies in animals and humans.]
Christina: What I think is so important about this is that as we learn more about the role that gut microbiota may play in our health, it’s really opening a lot of doors for us in terms of how we think about disease. Now, this is all pretty deep-dive biology so I’m curious if you ever share this kind of information with patients.
When I talk to patients about their symptoms, one of the major points I discuss is how chronic stress can contribute to flare-ups. Everyone gets it when you talk about stress…dysbiosis is a little bit of a different story. You don’t want to overwhelm them with information, especially if it’s a new diagnosis and they’re just wrapping their head around everything. But, if we’re talking about postinfectious IBS or discussing any past history of a viral gastroenteritis, or that patient who says they got really sick on a cruise 2 years ago. I think bringing up dysbiosis can be really important if we believe that these problems may have caused the patient to develop IBS-D.
Amy: I think you’re right, Christina. This information can be really valuable to our patients, but we obviously need to explain it in a way that makes sense to them and has meaning for them. And I’ll look for the same things as you—I’ll ask them, “Do you recall traveling or eating something that didn’t settle well and caused an episode of infectious gastroenteritis in the past? Did the symptoms seem to start sometime after that?” There is a subset of patients that I see where it’s like a lightbulb goes off when you ask them those questions, and they can recall an event.
Christina: Yes, I see the same thing. And the gut microbiome is certainly a topic that the general public is becoming more aware of. My patients definitely receive and accept education on the gut microbiome.
Amy: Exactly! I make sure that I allocate time to spend educating my patients, and I really try to focus on patient-friendly language. Metaphors can be useful to help explain what’s going on. For example, I’ll say “Just like a city needs different types of people, like clinicians, plumbers, and sanitation workers, it’s generally believed that the gut needs the right number of different species of bacteria to help keep everything running smoothly.”
Christina: That’s such a great point, Amy. And you know, some of these patients have seen multiple clinicians and have been dealing with this for a long time. Just letting them know “It’s not all in your head! There are real, biological causes for this” is really important.
Amy: Definitely, and not just seeing lots of clinicians, but, like you said, some of them have been dealing with this for a long time and sometimes that means they have been dealing with it on their own. A lot of my patients come in and have already tried a variety of different diets. Some diets can be very restrictive, and patients may not always find adequate relief with diet therapies. And you know, as a dietician, I’m not going to discourage trying diet modifications but if they’re not getting adequate relief, then it may be time for another approach.
A lot of my patients have also already tried over-the-counter therapies. Many initially think, “I don’t want to be on medications. I want to do this naturally,” you know, try different probiotics they have heard about or stress reduction techniques, yet sometimes their symptoms persist.
And I think a lot of this comes from the desire to avoid being dependent on a medication long-term and trying to find alternative options, since it is what we consider a chronic relapsing condition. So, I can definitely understand that concern.
Christina: So, this is actually a great time to move on to how we may be able to help treat our adult patients with IBS-D, so let’s take some time to talk about XIFAXAN. I want to focus on XIFAXAN particularly because it’s believed to affect a potential underlying factor of IBS-D we’ve been talking about.
XIFAXAN 550 mg tablets are indicated for the treatment of irritable bowel syndrome with diarrhea in adults and contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
As we discussed earlier, there are studies that show that many IBS-D patients have an imbalance in gut bacteria. I want to highlight one study in particular, which was a substudy of a US clinical trial. In this study, the majority of IBS-D patients had an abnormal composition of bacteria in the gut. (Data from 62/93 patients from a prospective sub-study of the TARGET 3 clinical trial.)
Although additional studies are needed to further understand the role of gut microbiota in IBS, XIFAXAN is believed to affect a potential underlying factor of IBS-D by directly attacking bacteria in the gut that may be linked to IBS-D symptoms. In fact, XIFAXAN is the only FDA-approved IBS-D treatment that alters the microbiome. It’s an oral, nonsystemic antibiotic–less than 1% is absorbed into the bloodstream–and it inhibits the growth of bacteria in the gut by inhibiting bacterial protein synthesis. It’s important to note that the mechanism of action of XIFAXAN is unknown and does not imply clinical efficacy.
I also want to point out that Clostridium difficile-associated diarrhea, or CDAD, has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. diff may need to be discontinued.
Additionally, although XIFAXAN is minimally absorbed from the gastrointestinal tract, it is important to note that there is an increased systemic exposure in patients with severe hepatic impairment and caution should be exercised when administering XIFAXAN to these patients.
So, when I’m talking to my adult patients about XIFAXAN for IBS-D treatment, I do think they are pleased to hear that even though XIFAXAN is an antibiotic, it’s nonsystemic. Like I mentioned a minute ago, less than 1% is absorbed from the gut. That’s an important point for me. When you’re talking to a patient for the first time about XIFAXAN as an IBS-D treatment option, Amy, how do you explain what XIFAXAN is and how it’s thought to work?
Amy: I always counsel patients on the fact that XIFAXAN is a nonsystemic antibiotic and explain what that means. But I always describe it as different than a systemic antibiotic you would take for an infection.
And, if my patients voice concerns about taking long-term therapies, I talk with them about XIFAXAN as a great opportunity to help treat their IBS-D because the recommended dosing is one tablet three times a day for two weeks. And patients who experience recurrence can be retreated up to two times.
Christina: I see the same thing in my practice. Patients like these may want to know more, so we talk a little bit about how XIFAXAN is thought to work. Like you mentioned earlier, analogies can be helpful, so I’ll say something like “Your gut is like a flowerbed with many kinds of flowers, but for some people with IBS-D, parts of their garden can become overgrown and other parts may not grow that well. XIFAXAN is like your gardener that can help you tend to your flowers.”
Amy: Yeah, I think for both types of patients—those who think a prescription medication isn’t right for them and those who are looking for something other than over-the-counter—it’s important to tell them about how XIFAXAN is just a 2-week treatment and that patients who experience recurrence can be retreated up to two times. I also mention that XIFAXAN has a well-established safety profile. In IBS-D clinical trials, the most common adverse reactions with XIFAXAN were nausea at 3% for XIFAXAN versus 2% for placebo and alanine aminotransferase increased at 2% for XIFAXAN and 1% for placebo. (Based on clinical trials in patients with IBS-D, individual response to treatment with XIFAXAN may vary.) Finally, I explain that XIFAXAN is a nonsystemic antibiotic. I really try to counsel patients on that, and that—while individuals’ responses may vary—this medication may help. I position it as “Think about what it would be like if we were able to find a medication that might help treat your IBS-D.”
I offer that perspective of, “Do you want to continue to just make do with your IBS-D? Or would you like to try a therapy that may help treat your disorder?”
Christina: That’s really what it all comes down to, right? Well, it’s been so great speaking with you today, Amy!
Amy: My pleasure!
Christina: Thank you so much for taking the time to share some of your insights around IBS-D. Now let’s provide an overview of the indication and full important safety information for XIFAXAN for those tuning in.