Introduction and the Evolution of IBS
So hey everyone, Josh from SIBO survivor and today I’m very fortunate, I’m joined by Dr. William Chey. A little bio on Dr. Chey before we get into the discussion today. So Dr. Chey received his BA degree from the University of Pennsylvania and medical degree and training in internal medicine at Emory University School of Medicine. He went on to complete a fellowship in gastroenterology at the University of Michigan and since completing this fellowship Dr. Chey has remained at the University of Michigan where he is a professor of medicine, director of the GI physiology laboratory and co-director of the Michigan bowel control program. Dr. Chey runs a very active clinical research group which has received funding from federal and private sources. He’s authored more than 200 manuscripts, reviews and book chapters. He’s a co-editor in chief of the American Journal of Gastroenterology and so many other accomplishments. So very fortunate to be able to sit down and talk with Dr. Chey and kind of just discuss IBS and how SIBO is connected and kind of clear up some confusion that a lot of patients and people have about these, about IBS and how it’s related to these other conditions so awesome to have you Dr. Chey and I guess, one question before we dive into the interview, what’s your focus now are you mainly research or you spend half your time as a physician or so what’s your specialty now?
Dr. Chey (1:55)
Yeah, so first of all Josh, thanks for having me on and it’s wonderful to talk with your audience. Me, I spend about half my time doing clinical work. So I’m still a real doctor with an active clinical practice and I spend about half my time doing a variety of other things, so research, mentoring the people in my research group and also the administration, you know I run a couple different programs here including a multi-specialty group that takes care of patients with pelvic floor and pelvic floor disorders like fecal incontinence or chronic constipation and also the nutrition and lifestyle program here.
Gotcha. It’s awesome, so you kind of have your hands in a number of different gastroenterology functions. So I guess to start off in this interview I want to focus on you know the definition of IBS, kind of how that’s changed and where it’s going. So I guess first of all what is the definition of IBS and how has this definition kind of evolved over time and where do you see it heading?
Dr. Chey (3:08)
Yeah, so first and foremost I think it’s important for everybody to realize that that IBS is not a specific disease it’s really a symptom based diagnosis that is predicated upon the presence of abdominal pain and altered bowel habits and you’re right that definition has actually changed a bit over time. So, for example, the criteria that we use to diagnose IBS are the Rome criteria and the Rome criteria in its latest iteration has actually moved more towards abdominal pain and away a bit from abdominal discomfort. Now that may seem like a pretty subtle difference but the reason we did that was because in some cultures, in some parts of the world, there are either no words or it’s very difficult for people to articulate the concept of abdominal discomfort and abdominal pain is a more universal theme. But the fact that the clinical phenotype, that is the range of symptoms that IBS patients can present with is so diverse. Think about it, abdominal pain, diarrhea, constipation or a mixture of both constipation and diarrhea says a lot about the fact that the pathophysiology is also likely to be heterogeneous or diverse in other words the cause for symptoms in you, Josh may be very different than the cause of symptoms for another patient that has really identical symptoms.
Definitely, and as a patient and I know a lot of other patients out there I think that’s maybe one of the most frustrating things it’s so complicated right there can be numerous different causes and everyone has a different situation. So you’re saying it’s it’s gone away from abdominal pain or?
Dr. Chey (5:06)
No, no, we’re very much focused on abdominal pain and we’re less focused on abdominal discomfort but you know the good news is the vast majority people that have abdominal discomfort also have abdominal pain so as it turns out it doesn’t have that much of an impact. I think from a pragmatic standpoint for your audience IBS is abdominal pain recurring bouts of abdominal pain over an extended period of time six months at least in association with altered bowel habits so the main subgroups are actually defined by bowel habit so IBS with diarrhea, IBS with constipation or IBS with a mixture of constipation and diarrhea.
Gotcha, so how do you think this definition will change going forward as we learn more about the condition?
Dr. Chey (6:02)
That’s a really interesting question because I think that you could certainly argue that we probably taken symptoms as far as they can take us in other words we’ve gone through several iterations now as far as the Rome process to arrive at the Rome foreign definition for IBS which is again based purely on symptoms now we use some diagnostic testing, but the diagnostic testing that doctors do in clinical practice is almost all aimed at excluding organic diseases that can masquerade or mimic IBS. So we do testing to exclude celiac disease or inflammatory bowel disease or colon cancer, a whole range of different organic diseases that can cause symptoms. Yes, I think moving forward where we’re gonna go is developing biomarkers that is diagnostic tests that help to rule in IBS. So symptoms aren’t going anywhere. Symptoms are always going to be the backbone that leads to the algorithm that defines IBS, but I think we’re going to be using symptoms plus biomarkers, biomarkers to exclude other diseases as we do right now but also bio-markers to rule in IBS and give us insight into the specific cause of symptoms in an individual patient. The reason that’s so important, I know we’re going to talk about this more a little bit later in the interview, it’s because when we do that when we have diagnostic tests to give us insight not only into the pathophysiology or cause of a patient symptoms we’ll have a much better chance of choosing the right treatment for the right patient.
Diagnostic Testing for IBS
Gotcha so that’s exciting as a patient. So, just to make sure I understand it correctly, so right now IBS is pretty much a diagnosis of exclusion, right? You’re excluding let’s say Crohn’s disease, celiac, making sure someone doesn’t have those other conditions that can kind of mimic the symptoms and then you’re saying moving forward we’re hopefully gonna head towards having specific diagnostic tests to actually help people show them what’s causing their IBS symptoms, correct?
Dr. Chey (8:26)
Exactly, and I think I think there’s a lot of the semantics like you know a lot of people say that IBS at the current time is a diagnosis of exclusion and to some extent that’s correct in the sense that the testing that we do is to exclude other organic diseases. That being said it’s important to realize though that not everybody needs exhaustive diagnostic testing, in fact, most patients that present with characteristic IBS symptoms and no warning signs or alarm features that is things like weight loss, bleeding, a family history of important organic diseases like celiac disease, colon cancer, inflammatory bowel disease. If you have characteristic symptoms and no warning signs or alarm features, it’s reasonable at a primary care level to conclude that a person has IBS and to try simple treatments. I would actually argue that it probably is worthwhile to do a blood count, some serology to exclude celiac disease and tests to exclude inflammatory bowel disease like a fecal calprotectin or a fecal lactoferrin, but really only limited tests. In other words, every patient doesn’t need a colonoscopy, every patient doesn’t need an upper endoscopy, every patient doesn’t need an ultrasound or CT scan. So when we say diagnosis of exclusion I just want to make sure that everybody understands that the exclusion part is quite limited to arrive at an accurate diagnosis of IBS, at least as a first step in treating patients.
The Connection Between IBS and SIBO
So next is can you explain the relationship between IBS and SIBO? Because a lot of you know Dr. Pimentel’s team and a lot of other researchers and doctors now are, SIBO has kind of become the hot term right and I really think it’s important for people to understand the connection and not to kind of confuse them, right?
Dr. Chey (10:40)
Yeah, yeah so this is obviously you know we used to say it back in the old days it’s a million dollar question now it’s the billion dollar question, right, I mean so this issue about the relationship between IBS and SIBO there is clearly a relationship there. Now, the nature of the relationship remains to be completely defined. I think it’s really important for people to understand that while there’s an association, it doesn’t necessarily prove cause and effect at the current time. So let me explain to you what I mean by that part of the confusion around SIBO and IBS. There’s no question that there’s a higher likelihood of IBS patients having SIBO on the basis of breath testing, for example, compared to the general population. But the next step of the question is is SIBO the chicken or the egg, in other words, is it that SIBO causes the IBS symptoms or is it that the underlying abnormalities in patients with IBS predisposed to the development of SIBO. The truth is, it’s probably a bit of both right? So it’s probably that patients with IBS may very well have abnormalities in motility and they have an immune system that predisposes them to developing SIBO and that SIBO leads to or exacerbates or worsens IBS symptoms. So it’s probably both. But it’s not as simple as people are making it out to be as I think is a key thing right now.
Yeah, definitely and it’s kind of tricky sometimes as a patient when you hear those two terms just because I, from my understanding, the way I kind of understand the research that’s been out there is that you know like you’re saying it could be the case right that food poisoning causes the nerve damage which then SIBO is an aftereffect, right, so it’s very tricky and I think people need to keep in mind that there are other issues going on and SIBO could just be a state in their gut that happens because of those other issues, right?
Dr. Chey (13:06)
That’s right, it’s a complicated issue for some patients. Clearly, identification of and treatment of SIBO is incredibly beneficial. Obviously, there are many patients with IBS that don’t have evidence of SIBO at least on the basis of breath testing or even quantitative culture and there are also patients that have evidence of SIBO where you treat it and their symptoms don’t get better. So I think the key thing just for everybody to recognize is it is a potential solution it’s worth going after particularly in the diarrhea-predominant or bloating predominant patients, but it’s not the solution for everybody. Not all IBS is SIBO.
IBS Causes and Conditions
Yeah gotcha and so I guess one question coming off of that is let’s say someone in my audience has tried antibacterial treatments or things to kind of treat SIBO right and they’re not getting better, right, it’s recurrent and does that mean they should really kind of talk with their doctor or realize that maybe just treating SIBO is probably not the best solution for them?
Dr. Chey (14:26)
Yes, absolutely and you know in the day and age of FDA approval for non-absorbable antibiotics like Rifaximin, so in other words people using it much more ubiquitously in clinical practice. The patients that I’m seeing more and more are exactly like the ones you’re describing. See, it used to be you know five or seven years ago that the patient’s I would see had not been tested and not been treated with antibiotics strategies and a lot of them got better. But now the patients that I’m seeing have almost all gotten antibiotics and they have persistent symptoms and so the question is, why is that the case is it persistent SIBO, or is it that it’s not SIBO related and it’s some other mechanism that’s responsible for symptoms that we would characterize as consistent with IBS, and you know many times it’s the latter that’s the case.
Yeah and that’s very interesting and very good for my audience to understand because you know if you’re dealing with a chronic issue and you’re trying like one thing right it’s just it’s recurring and you’re treating it like that you know it’s probably a smart thing to focus on, okay IBS what are the underlying causes besides this and what can we do to kind of improve that, So I guess the next thing to talk about here is what are the main underlying issues you see in IBS patients maybe where SIBO isn’t an issue and then the patient’s where maybe you suspect that SIBO actually is an issue?
Dr. Chey (16:10)
Yeah, that’s a really great and important question that’s really hard to answer, in the sense that I think that we as doctors as a medical community because it’s just literally every time I speak about this nationally and actually this question comes up and it would be great if we had a really defined answer. I can tell you that the large phase three studies that were conducted with Rifaximin for example, we’ve tried to find clinical features a phenotype that identifies patients that are more likely to get better with Rifaximin for example. We’ve also done that in our diet studies and you know what I can tell you is for Rifaximin patients that present with, most questions would say, experienced clinicians would say focus on the patients that have a lot of bloating flatulence and diarrhea, but there are many patients that don’t necessarily have that phenotype that also will get better with that strategy. I think for diet interestingly you know we found that pain and bloating are the symptoms that are most likely to improve with, like for example the low fodmap diet, so you know it’s pain and bloating are sort of the big ones that we tend to think about it and go after, but they’re not universal truths.
Gotcha, so I guess, do you see that motility is an issue for a lot of IBS patients or is there anything else that you see where you know it could be kind of setting them up for this bloating and pain, any other underlying issues?
Dr. Chey (19:02)
Yeah, you know if you think about, so back in the 1990’s when I was in GI fellow at Michigan I was taught that IBS was a condition that was really largely attributed to abnormalities of motility or the contractile activity of the GI tract. Visceral hypersensitivity, so this concept that IBS patients are hardwired differently so that they’re more sensitive to a variety of different kinds of stimuli whether you’re talking about food or stress, medications, where they’re more likely to develop symptoms with the same level of stimulation that an otherwise healthy person would receive and experience no symptoms and then on brain-gut interactions, so this idea about the communication between the brain and the GI tract and you know which is why stress is such an important factor for many IBS patients. I think as time has gone on we’ve talked about many other things, alterations of permeability, activation of the immune system, dysbiosis or alterations in the microbiome which is obviously relevant to bacterial overgrowth. By the way, when you think about the microbiome you could be talking about the location of where the bacterial contamination is occurring, so bacterial overgrowth is a great example of that where you have contamination of the proximal small bowel that leads to premature fermentation and all the consequences of that. But also remember that the other factors may also be relevant although this is less well understood and that is the composition of the communities so not just the location but what bacteria is there and also the quantity of bacteria that’s in there. So there’s a lot of variables to really put into the equation that we don’t really have a great understanding of at the current time. I do think that a lot of the pathways, even these new pathways permeability, immune activation, dysbiosis can impact upon motility which can lead to the development of symptoms, particularly in an individual with visceral hypersensitivity. So what I would just really emphasize is, all of these potential factors that we have implicated as potentially important in the pathogenesis of IBS are likely intertwined. They’re not independent variables, they’re codependent variables that interact to different degrees and different patients. And that’s what makes it so complex.
That’s what I was gonna say, that’s why it’s such a complicated condition because you’re saying there are all these co-variables or one thing could have shifted the other and then they kind of domino effect.
Dr. Chey (21:05)
And that’s why I think you know by the way Josh, that we really need to move towards (if we can, it’s not gonna be easy to do this by the way it sounds sort of conceptually very simple but it’s practically going to be very hard.) But we need to move towards a model where we develop biomarkers that help us understand how these different things are inter-playing and which of these factors are most important in an individual patient, so we can choose the right therapy for the right patient.
The Microbiome and IBS
Gotcha, I guess on the microbiome topic, what, as what you’ve seen you know the testing available now and the research that’s going on what, what do you see that you know we need to get a better picture of , you know, bacterial flora because we’re missing a lot right now, is that correct?
Dr. Chey (21:03)
Well yeah because I think that again, for example, a lot of the commercial tests that are out there and obviously you know there are a lot of commercial test that are out there now that claim to be able to provide a detailed microbiome analysis and not just a microbiome analysis, but interpret what that means. I’m skeptical about that at the moment given where the science is at the current time. I’m hopeful that we will be able to get to that point but simply quantifying certain species, strains, families and bacteria probably isn’t detailed enough to really give us insight into how they interact. In other words, the communities may be important, may be just as important as the individual constituents because the interaction you know between the individuals that live in the neighborhood may very well play a really important role to the degree of harmony that exists within the community, right? I mean think about it just in terms of your own neighborhood. You may understand the individuals but it’s not necessarily how you know the individuals as much as how they interact within the community that they live. So right now the testing does not do that. The science is really not at a point where we’re able to do that, but it’s a very important factor that people need to take into consideration, as people are trying to tell them that they can interpret the results of a microbiome analysis that simply tells them how much of each strain is present in their stool. The other thing is to remember that the stool microbiome you know which is what we can measure right now may or may not be the business end of where the microbiome is interacting with the host and leading to beneficial or detrimental things people have been talking more and more about. For example, the mucosal microbiome compartment you know the microbiome in your stool just represents the stuff that’s in the lumen and a lot of it is dead. There’s a whole different microbiome that’s living on the lining of the GI tract that is actually directly interacting with the immune system and affecting things like permeability, neurotransmitters that are responsible for the function and sensation in the GI tract and that you know we know very little about. That we can’t really measure that at the current time.
Very, very interesting and it’s really good for people to understand. So, I mean basically right now the microbiome tests are kind of just, you know, there’s no clinical relevance right now for those tests, right?
Dr. Chey (24:55)
I agree I think, put it this way, I think that it’s really important for people to not try to over-interpret those results. I think you know you may very well be able to get some general information, you know like for example in regards to diversity, you know you can get some very general ideas about the health of your microbiome, but in terms of making specific recommendations and for example recommending that you need to increase this or decrease that. Boy, I think you’re not on solid ground in terms of the science at the current time.
Yeah, it makes sense it’s just fascinating to me to kind of think about what you were saying the analogy of a community in your neighborhood and even how complex that is with different people and different you know the way they live their lives. One guy’s a doctor, one guy builds homes, and it’s very complicated the way the interaction works and you know it potentially could be something similar in your body. We don’t know yet.
Dr. Chey (25:56)
I agree and you know take extending this a little bit and just thinking about the next step, it may very well be that the metabolomics are more important than the actual microbiome analysis. Like, in other words, the metabolomics the metabolic consequences of the interactions between the constituents of the microbiome may very well represent again that business end in terms of what’s happening in the GI tract. People are just starting to look at at metabolomics, things like volatile organic compounds these these things are very promising, very interesting, still very preliminary.
Visceral Hypersensitivity and Motility
Gotcha, so back IBS a little bit here, so I’m curious about this, if any research you’ve done or anything that’s been studied. So is there any reason why the abnormal sensation or visceral hypersensitivity and the motility, what is kind of the research shown that why IBS patients have those things?
Dr. Chey (27:05)
So there’s a there’s a lot of theories. I think that a couple ones that are pretty well established at this point are early life trauma, so that can either be physical abuse, verbal abuse, sexual abuse that leads to alterations and hard-wiring of the nervous system that while the nervous system is still developing during childhood that seems to predispose to the development of IBS. Genetics, people have talked about a lot I must say that there’s been a lot more smoke there than fire but increasingly there are descriptions of polymorphisms in the genome that predispose the development of IBS so that may very well be an inherited predisposition towards IBS based upon our genetics. And then the alterations in the microbiome I think are quite fascinating. You know you alluded to the group of patients, the well-defined group of patients, with post-infectious IBS. This population of individuals that get an acute gastritis and by the way, it’s I think a really important observation, interesting observation, is the fact that it doesn’t have to be bacterial gastritis. It actually can be either a viral or parasitic gastritis. Anything that revs up the immune system in the GI tract can lead to an increased likelihood of developing IBS. And so the idea there is that the infection activates the immune system, changes motility and visceral sensation and when the infection is gone those things are supposed to go back to normal, but in seven to fifteen percent of individuals who develop a severe acute bacterial gastritis that it doesn’t go back to normal it continues to be abnormal with development of abnormalities of motor function, contractile activity and visceral sensation, predisposing the development of IBS symptoms.
Post-Infectious IBS and SIBO Treatments
Very interesting. So I’ve heard a lot of percentages thrown around about how many patients are suspected to develop IBS from that. What, I mean, what would you say the percentage of post infectious IBS and that can also be considered SIBO, correct? That’s kind of what most doctors are considering it and like what percentage-wise what you say of the IBS population?
Dr. Chey (29:50)
Yeah, well first want to clarify. So it may or may not be SIBO. Certainly patients with post-infectious IBS are likely to be predisposed to developing SIBO for all the reasons we’ve already discussed, but there are many patients in which they have a clear history of infection. You do a detailed diagnostic evaluation, including an evaluation for SIBO and you don’t find any evidence of SIBO. So my suspicion is that you are correct that there’s probably an even higher likelihood of SIBO among individuals that have a post infection etiology but it’s not a universal theme among those individuals. That’s the first thing just to recognize. I don’t want people to think that if they have a clear history of gastritis that preceded the illness that they need to retreat over and over again with antibiotics for example. They may or may not, so and I worry that that happens sometimes and I also worry that may be creating more problems than its solving, because another interesting observation is that particularly kids that get repeated courses of antibiotics are more likely to go on to develop IBS. So antibiotics are the solution for some, may be the problem for others and it’s just very important for people to understand that.
Yeah, it really is because I think that’s so important that point because just in general the term SIBO has kind of taken off and a lot of people and even doctors that I’ve heard are focusing a lot on just antimicrobials and I think it’s so important to remember that there are other causes. There’s people you know like you’re saying it’s not the case that everyone just needs to take antibiotics.
Dr. Chey (31:51)
I agree and I think another really important theme again has to do with remembering that the evidence is for the non-absorbable antibiotic Rifaximin. Now that doesn’t mean that other antibiotics aren’t going to work. In fact, we know that for some patients other antibiotics work and in fact there are studies, for example, from India with Norfloxacin, but a really important thing just to remember is that Rifaximin is not absorbable so it does not get into your bloodstream and will not affect bacteria in other parts of your body. That’s important because of course what we’re talking about is bacterial overgrowth or alterations in the microbiome within the GI tract. And you know obviously the lack of exposure of other bacteria in the body to the antibiotic is a good thing because A we’re not trying to alter those bacteria and B we’re not predisposing to the development of microbial resistance down the road you know when we’re talking about using systemically absorbed antibiotics like Amoxicillin, Ciprofloxacin, Metronidazole, etc you know there’s a very different type of concern there, because you know those antibiotics get into the bloodstream, will affect bacteria all over the body and are predisposing to the development of antimicrobial resistant bacteria that could cause pneumonia or skin infections, you know all sorts of different other issues. So in my mind the best treatment and the most evidence-based treatment right now for SIBO and for IBS is Rifaximin. And people should be careful particularly about being treated recurrently with systemic antibiotics. Sometimes that’s the only option related to cost but you know where it is an option to use Rifaximin and I think we’re probably best off doing that at least until we learn more.
Yeah. So would you say the bottom line is that really if you’re going to be using antibiotics, be careful because we don’t know about the risks that come with them and how they really affect our overall microbiome, right?
Dr. Chey (34:15)
I couldn’t have said it better. I think that’s really sound advice. I think it’s really important for people to understand that we’re really at the start of this whole journey, not at the end. The data that’s shown that the microbiome plays an important role for some patients is that using things like probiotics, prebiotics, antibiotics, diet, which all affect microbiome reinforces this concept that for some IBS patients the microbiome is a key player in terms of pathogenesis and symptom experience, but it’s not the only solution. And we don’t have the level of precision that I think we should all feel reassured by. So think about it if you’re talking about probiotics antibiotics or diet, the therapeutic rate over SIBO is around 10 optimistically 15 percent. Yeah, that’s a statistically significant difference but realize that’s pretty close to and maybe only a little bit better than around half of the patients getting better, which means around half the patients aren’t getting better. So again going back to that whole part you know the discussion we had at the very beginning, right? We need to come up with better diagnostic tests not better treatments, better diagnostic tests so we can choose the right treatment for the right patient.
Yeah and that way we know if someone would actually benefit from the antibiotic treatment, right?
Dr. Chey (35:50)
Right, so I guess just off of that point, so right now in IBS, as far as treatments go, what are kind of the categories that you treat? So there’s the microbiome that some people may find helpful, those treatments that we kind of just talked about, what else do you do right now to help IBS patients?
Dr. Chey (36:16)
Well, I think the big thing in my mind that’s really changed in terms of IBS therapy, so there’s some very effective medications which target specific pathways, opioid pathways. serotonin pathways, cholinergic pathways, brain-gut interactions, like antidepressants, but I think the key thing for patients to understand is particularly those with moderate to severe symptoms is that we’re moving towards more of a holistic integrated model. So not just medications, but also taking into consideration diet and lifestyle. So for example you know obviously there’s been a lot written and talked about with diet therapy so the one that’s received the most attention right now is low fodmap, but also behavioral therapies are really coming to light as incredibly effective for many patients. By the way not only patients who are you know clearly depressed and anxious, but also patients in which stress is an important exacerbate or trigger for symptoms, helping patients to recognize that helping patients to have strategies to manage that can be life-changing. So it’s not uncommon at all for me in my practice now in my group we have specific GI dietitians, we have specific GI behavioral therapists, in addition to the medical doctors as well as physician’s assistants and we work as a team to come up with the right solution for an individual patient. Sometimes that’ll be more diet focus, sometimes they’ll be more behavior focused, sometimes I’ll be more medication focus, sometimes it’ll be all of the above. But when you have moderate to severe symptoms that aren’t getting better with over-the-counter remedies, maybe the standard prescription medications, you really should be thinking about being seen in a center or a practice where they’re taking a more holistic, integrative approach.
Yeah, definitely, just because kind of like we talked about IBS is so complex, right, and all those things we talked about and I as an IBS patient I’ve experienced the brain symptoms. It kind of all goes hand-in-hand and it really is important for people out there people watching this that if you’re not getting better, you’re having recurrent issues need to kind of work like Dr. Chey is saying more towards the holistic approach and kind of integrating all these different factors to find relief. Is that fair to say?
Dr. Chey (39:00)
Yeah, I think that’s totally fair to say and a good place to end.
Yes. Well thanks so much Dr. Chey for joining us and good luck in your research and your practice and I’m excited about the future of IBS treatment as well.
Dr. Chey (39:18)
Me too and I hope your patients are taking away a hopeful message because I think the future for IBS patients is going to look a lot different than the past for IBS patients.
Yeah, I’m excited about the diagnostic testing too, right, getting more specific about why someone’s having those issues and kind of dialing that in, so thanks so much for joining me.
Dr. Chey (39:40)
Take care Josh we’ll see you.