A source for healthcare professionals to access the latest data and information on the diagnosis, treatment and management of patients with gut related disorders

Video series

A series of video presentations exploring information relevant to gastroenterologists, including summaries from key conferences.

Irritable bowel syndrome (IBS) is a disorder of exclusion: An extensive diagnostic work-up is necessary
Professor David S. Sanders 

Professor Sanders highlights that many patients presenting with irritable bowel syndrome (IBS) have underlying diseases. He explores why patients do not always benefit from having treatments that are well recognised for IBS and notes that some patients may in fact have another diagnosis, disease or disorder.

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Hello, my name is David Sanders and I am the Professor of Gastroenterology at the Royal Hallamshire Hospital and the University of Sheffield. My research interests encompass Coeliac disease, IBS-type symptoms and bile acid diarrhoea. And so this brings me what I’d like to talk about, which is I’d like to share with you my own personal experience and the data in this field.

What I’m going to talk to you about today is about IBS and I want to make you think about it perhaps differently over the course of this talk.

If you are fans of cinema, as I am, then you will have watched ‘The Matrix’ and you will know that Morpheus very famously offers Keanu Reeves a choice, a choice between the ‘blue pill’ and the ‘red pill’ and if you take the blue pill then your concepts or your structures in medicine perhaps don’t change, but if you take the red pill, I would like to suggest to you that maybe you will open your eyes in a different way.

So with that in mind, let’s think about the Rome IV criteria for irritable bowel syndrome. Now as you know the IBS criteria have a long history and they have been carefully designed and the purpose of these criteria is to make a positive diagnosis. In other words, patients should have few tests and by using these symptom-based criteria, you should be able to come up with a diagnosis in your patients of irritable bowel syndrome.

But I have always struggled with this, and the reason is this: If you look at the next slide that I’ve put up then you can see that I’ve created different pathophysiological mechanisms for IBS, which I think we would all agree are entirely valid and that there is a strong publication literature base behind them. But the question I have to ask is: Why is it that our treatments for IBS have a high placebo response and often don’t work? And why is it that our practice and investigations do not always yield the findings we would hope for?

Let me make sense of this. Here in this study published in JAMA, you can see that the investigators have spent some time looking at the yield of diagnostic tests in IBS and of course things like colonoscopy that we undertake and the baseline biochemical and haematological profiles have a very low diagnostic yield. Yet everybody would agree that this is standard practice. So what you are then left with is a patient that’s had a series of likely normal tests and maybe they will be reassured by that, but their symptoms are persisting, and I’ve made a joke about this in this slide really suggesting that at the end of this process, your patient is far from happy. Yes, they may come for reassurance, but they would also like resolution of their symptoms.

So my question to you is: What if your patient doesn’t actually have IBS? Now I want to be very clear about this because I have a distinction in my mind about IBS-type symptoms and irritable bowel syndrome itself. Some may say that I’m a heretic, that I have a different view, something quite different from the current perspective of thinking, so let’s go and look at the next few slides and see if we can make sense or assess this perspective.

Here we have a systematic review and a number of studies published, looking at the diagnostic yield of coeliac serology when testing individuals with IBS-type symptoms. In the United Kingdom, 40% of our outpatient workload, or there abouts, equates to patients presenting in this way and most of them are given a diagnosis of IBS at the end of this process. This slide is very dear to me because it also puts forward some of the early work, done here in Sheffield and published in the Lancet.

We were the first investigators to describe the association between IBS-type symptoms and Coeliac disease, and I can tell you that at the time it was widely viewed that this was a stand-alone study and that this should not change practice. But it took a decade and numerous other investigators and international studies publishing in this field, to finally clarify that indeed patients with undiagnosed Coeliac disease could present with IBS-type symptoms and in the United Kingdom, NICE (the National Institute for Clinical Effectiveness) now says it is mandatory to test individuals who present in this way with IBS-type symptoms and exclude Coeliac disease.

That journey took 10 to 15 years and it shows you that maybe there are patients lurking in your practice who actually have other diagnoses. Now, if you are relatively new to the field of gastroenterology you will already be undertaking these tests as part of your normal practice, but the story dates back to the late 90’s and gives you a reflection of how medicine changes and how sometimes it can be very slow.

Let’s now turn our attention to small bowel bacterial overgrowth. The main author in this field has been an American by the name of Mark Pimentel and initially when he established an association between small intestinal bacterial overgrowth (or SIBO) and individuals presenting with IBS-type symptoms this was widely refuted.  At the beginning he used lactulose hydrogen breath tests and it was felt that perhaps this wasn’t the relevant test. He then went on to show the benefit of antibiotic therapy in these individuals and again the same methodological limitations were pointed out. Pimentel then published in the New England Journal of Medicine, a multicentre North American and Canadian study.

Now, he dispatched with the breath tests acknowledging their limitations but in this study, he took individuals with IBS-type symptoms (and we’re talking about 1,260 patients here) and he gave them rifaximin and he demonstrated there was a response at 4 weeks. It was a fairly high placebo response as well but at the end of the day a 40% response for your patients.

Other investigators in the IBS-type field said, Well, how can we be sure that this is SIBO when we haven’t tested for bacterial overgrowth? and although that I acknowledge that is true, nevertheless he has shown symptomatic benefit in his patients in a huge, very well powered study. It may well be that the antibiotic is treating bacteria elsewhere, perhaps colonic bacteria but there is a story there and I think this gives us a further opportunity to treat individuals who present with IBS-type symptoms.

Now, let’s look at faecal pancreatic elastase. Again, this is a stool test which looks at pancreatic enzymes and tries to look for a deficiency in the production of these enzymes. Individuals who have exocrine pancreatic insufficiency, and are not producing enough pancreatic enzymes, frequently have maldigestive or gastrointestinal symptoms.

What we have shown, in a cohort of 300 patients with IBS-type symptoms, is that a percentage of them will in fact have undiagnosed or unrecognised exocrine insufficiency. Furthermore, by giving these individuals pancreatic supplements their symptoms improved.

We went on then to take a more global approach and look at all patients presenting to outpatient clinics, irrespective of their gastrointestinal symptoms and once again showed a high diagnostic yield for exocrine insufficiency and other workers as you can see from this slide have validated the results that we have described. So I’m putting this question to you that here is another diagnosis frequently not considered or not tested for which may be lurking within the patients you see with IBS-type symptoms.

Now, I would like to look at bile acid diarrhoea. This particular slide reflects a systematic review of the diagnostic yield of SeHCAT in patients as it’s described as chronic diarrhoea or IBS-type symptoms. So I entirely accept that this is a very mixed, or heterogenous group of patients. Nevertheless, as you can see, by highlighting in red as I've done, there is a signal there and the prevalence is something like 25–32%, but I appreciate the limitations of this study.

Since that time a number of investigators have published their retrospective studies looking at the yield of SeHCAT in patients with IBS-type symptoms and once again the range seems to be coming out at about 25% and I’ve put up three separate studies, including Sheffield data.

Many investigators said, Well, it’s retrospective so perhaps there is a clear ascertainment bias. Maybe those patients you selected to send for SeHCAT were ones with whom you had a suspicion because there were other features involved, and I completely appreciate this criticism, it’s valid.

So, we went on to take this a little further and in this unique multicentre study or dual centre study where the two cities of Leeds and Sheffield 40 miles apart, with different investigators in different hospitals, set out to prospectively recruit more than 100 individuals who presented to our clinic, referred by GP’s, in an unselected way with IBS-type symptoms, and what did we find, well the headline was: 23.7% of them had previously undetected bile acid diarrhoea.

So, imagine, these are two centres running the same study but not actually using the same investigators but recruiting in an identical manor. So, I think this is very strong data that suggests that maybe a quarter of your patients who you are seeing with IBS-type symptoms have unrecognised bile acid diarrhoea and for me it’s a practice changing paper.

We are not the only ones to have made this observation. Magnus Simren and his group in Sweden in Gothenburg, have now published a very similar data set, again showing the diagnostic yield and symptomatic response when bile salt replacement therapy was given. So this is emerging work and practice changing work.

Finally, I’d like to consider microscopic colitis. If this is not a condition that you have come across before it is specifically a diagnosis made by taking biopsies at the time of colonoscopy.

When you look at the bowel with the naked eye it may well look normal and the slide that I have put up here, has tried to see what the diagnostic yield is when you take this approach in your IBS-type patients and it suggests that maybe it accounts for 7% of that group.

So, ladies and gentlemen, what I would suggest to you comes back to what I said at the beginning: Would you like the blue pill, or would you like the red pill? If you opt for the red pill, then please consider changing your practice. Think of the patients who come to you, to see you in clinic, as individuals who have IBS-type symptoms, not as patients who have IBS. There is a difference, and when you have put them through an investigation triage, looking for Coeliac disease, looking for bile acid malabsorption, looking for exocrine insufficiency, looking for bacterial overgrowth and microscopic colitis, the size of your patient group will become smaller. You will have recognised different disorders and diseases that you can treat for and those patients will benefit from that intervention. You will then be left with a smaller group of patients, who yes, I acknowledge do have IBS but I am very hopeful that when you are left with that group, the treatments you then institute will be beneficial to them. So, it’s a choice, The blue pill or the red pill? Thank you very much.

Job number: JB57410GBa Date of Preparation: August 2019

Let's talk about irritable bowel syndrome (IBS)
Professor David S. Sanders 

Professor Sanders highlights that many patients presenting with irritable bowel syndrome (IBS) have underlying diseases. He explores why  patients do not always benefit from having treatments that are well recognised for IBS and notes that some patients may in fact have another diagnosis, disease or disorder.

Read More


Mechanism of bile acid diarrhoea
Professor Julian R.F. Walters

Professor Walters explores the classification of different causes of bile acid diarrhoea (BAD). Professor Walters describes the normal entrohepatic circulation of bile salts and what occurs when the system does not function correctly. 

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How common is bile acid diarrhoea (BAD)?
Professor David S. Sanders 

Professor Sanders argues that many patients presenting with irritable bowel syndrome (IBS) have underlying diseases. He explores a series of studies that suggest approximately 25% of patients presenting with IBS symptoms have BAD as the underlying cause. 

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Bile acid diarrhoea: who should I test 
Professor David S. Sanders

Professor Sanders discusses which clinical scenarios might warrant investigation for bile acid diarrhoea (BAD) and how this could improve treatment for these patients.

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Pathophysiology of bile acid diarrhoea
Professor Julian R.F. Walters

Professor Julian Walters discusses the pathophysiology of bile acid diarrhoea with regards to ileal disease and ileal resection; he also discusses primary idiopathic bile acid malabsorption diarrhoea.

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