YEAR IN REVIEW IBS IN 2014

Developments in pathophysiology, diagnosis and management Peter J. Whorwell

IBS affects up to 15% of the population and continues to provide the medical profession with diagnostic and therapeutic challenges. The pathophysiology is complex and until it is better understood management strategies will necessarily remain rather empirical. Whorwell, P. J. Nat. Rev. Gastroenterol. Hepatol. advance online publication 23 December 2014; doi:10.1038/nrgastro.2014.225

The quality of life of patients with IBS seen in secondary care is worse than that experienced by individuals with end-stage renal disease, diabetes or depression.1 In addition, the burden of the disorder is made worse by the fact that ~50% of these patients report faecal incontinence, which is even experienced by those with the constipation subtype.2 2014 has seen some important advances in understanding the pathophysio­ logy, diagnosis and m ­ anagement of this ­difficult condition.

‘‘

…IBS is at last beginning to receive the attention it deserves…

’’

One of the most plausible pathophysiological models is that patients with IBS have a genetic predisposition to gastro­ intestinal hyper-reactivity, which remains largely asymptomatic until a triggering factor(s) is encountered. A genetic component is possible as evidence suggests that many patients with IBS have an affected relative. However, studies on twins indicate that inheritance accounts for some, but not all, of the observed familial clustering, suggesting that patients might learn abnormal attitudes towards gastrointestinal symptoms from those around them, particularly during childhood.3 Alternatively, IBS has been suggested to represent the final common symptom pathway of a number of distinct entities and that once all these entities have been identified the condition will no longer exist. For instance, bile acid malabsorption is known to cause diarrhoea and its importance in IBS has been emphasized

by a study in 2014 showing its adverse effects on colonic function.4 Interestingly, patients with IBS and bile acid malabsorption had higher BMIs than patients without IBS, raising the possibility that increased bile acid synthesis in response to being overweight leads to saturation of ileal reabsorption. However, whether treating bile acid diarrhoea leads to a complete resolution of symptoms or whether an underlying ‘instability’ of the gut already exists and bile acid is merely acting as an exacerbating factor in IBS remains to be determined. A whole variety of triggering factors for IBS have been described, with one of these being an episode of gastroenteritis of either bacterial or viral origin. Such an event might lead to dysbiosis of the gut microbiota, which is now the focus of much attention both in IBS and other gastrointestinal diseases. There has been much speculation, particularly in the lay press, that infection with parasites such as Blastocystis might also have a role in the pathogenesis of IBS. Consequently, it is timely that in a 2014 study comparing the prevalence of parasitic infection in 124 patients with IBS and 204 healthy controls, parasites— including Blastocystis—were actually more common in the control group.5 However, before dismissing the role of Blastocystis completely, one must remember that in the field of peptic ulceration, far more patients harbour Helicobacter pylori than develop an ulcer; this finding highlights the fact that cofactors are sometimes necessary for disease expression and, for example in IBS, the state of the existing microbiota or genetic make-up might make Blastocystis more pathogenic. IBS is notorious for imposing a huge economic burden on health-care systems,6

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Key advances ■■ The importance of considering bile-acid diarrhoea in the management of IBS is becoming increasingly recognised4 ■■ Gastrointestinal infections seem to be a triggering factor in some cases of IBS but the role of parasites is less certain5 ■■ Faecal calprotectin levels show considerable promise in reducing the need for colonoscopy in the assessment of patients with probable IBS7 ■■ Changes in the circadian rhythm can affect functional gastrointestinal disorders and might also lead to changes in the gut microbiota8 ■■ Fermentable carbohydrates in the diet can exacerbate the symptoms of IBS and influence the composition of the gut microbiota10

which is partly due to the limited number of available treatment options but also because of the lack of a diagnostic test for the condition. As a result, patients are subjected to a large number of investigations to exclude other possible explanations for their symptoms and these are often repeated, especially if the patient fails to make any progress. In particular, the majority of colonoscopies performed on young people are undertaken to exclude IBD, with the result usually being negative. This wasteful practice could be transformed by the introduction of testing the faeces for calprotectin—a protein contained in neutrophils that reflects inflammation in the gut. In the past few years an increasing number of reports have confirmed the utility of this test and this year has been no exception.7 So far, the test looks extremely promising for distinguishing IBS from IBD, especially when it is ‘negative’. However, more clarity is needed around what constitutes a ‘positive’ test and whether false-positives can occur, especially as some drugs (such as PPIs and NSAIDs) can cause a modest increase in faecal calprotectin levels. In addition, it should be emphasized that this test has no role in the diagnosis or exclusion of colon cancer and is therefore more a­ppropriately applied to young patients. The management of IBS is not easy but an important component is education and advice on lifestyle such as ensuring some degree of exercise, coupled with regular meals and sleep. Consequently, it is possibly ADVANCE ONLINE PUBLICATION  |  1

YEAR IN REVIEW not surprising that a common clinical observation is that patients with IBS do not seem to tolerate working irregular hours, and functional gastrointestinal disorders have been shown to be more common in shift workers. This observation has now been taken a step further by a study this year in nurses that suggests that there is an interaction between psychosocial distress and rotating shift work in relation to the development of IBS or functional dyspepsia. 8 Evidence exists that changes in the circadian rhythm, such as those imposed by shift work, can result in changes in the microbiota9 and this finding offers one possible mechanism by which working irregular hours might ex­acerbate the symptoms of IBS. Many patients with IBS are frequently advised to increase the amount of fibre they consume, but good evidence now indicates that fibre, especially of the insoluble variety, can actually make their symptoms worse. Furthermore, some patients claim that they feel better on a gluten-free diet despite the fact that a diagnosis of coeliac disease has been excluded. This assertion is often dismissed but perhaps it needs to be re-considere­d in the light of a series of publications on the concept of non-coeliac gluten sensitivity. There has been an explosion of interest in the so-called FODMAP diet (Fermentable Oligo­ saccharides, Disaccharides, Monosaccharides And Polyols), which involves the exclusion of these carbohydrates that are widely

distributed, especially in fruit and vegetables (Figure 1). Polyols, such as sorbitol and xylitol, are also now widely used by the food and drink industries as sweeteners. Excluding FODMAPs from the diet no doubt benefits a substantial proportion of patients, and this approach is now being widely adopted. However, the great enthusiasm for this diet specifically, raises the possibility that other dietary manipulations, such as fibre reduction, might be ignored, which is likely to limit the full potential of the dietary approach to managing IBS. Importantly, a large number of patients with IBS are starting themselves on a FODMAP diet on the basis of information derived from the internet, which might not always be accurate. It is, therefore, advisable that health-care professionals who are involved with the management of IBS familiarize themselves with this intervention. A 2014 study has shown that reducing FODMAP intake increases faecal pH and leads to greater faecal diversity as well as reducing total bacterial abundance compared to a normal diet.10 It remains to be determined whether there any long-term consequences of this change in the gut microbiota, particularly as some patients only seem to have improvement of symptoms for as long as they adhere to the diet. The steady stream of research observed in 2014 confirms that IBS is at last beginning to receive the attention it deserves, especially as it is such a common and intrusive disorder.

Figure 1 | Some FODMAP-containing fruit and vegetables. Abbreviation: FODMAP; Fermentable Nature Reviews | Gastroenterology & Hepatology Oligosaccharides, Disaccharides, Monosaccharides And Polyols.

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Education and Research Centre, University Hospital of South Manchester, Southmoor Road, Manchester M23 9LT, UK. [email protected] Competing interests P.J.W has acted as a consultant for, or received research grant support from, the following pharmaceutical companies: Abbott, Almirall Pharma, Boehringer–Ingelheim, Chr. Hansen, Danone Research, Ironwood Pharmaceuticals, Norgine, Proctor & Gamble, Shire UK and Sucampo Pharmaceuticals. 1.

Gralnek, I. M., Hays, R. D., Kilbourne, A., Naliboff, B. & Mayer, E. A. The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology 119, 654–660 (2000). 2. Atarodi, S., Rafieian, S. & Whorwell, P J. Faecal incontinence—the hidden scourge of irritable syndrome: a cross sectional study. BMJ Open Gastro. 1, e000002 (2014). 3. Levy, R. L. et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology 121, 799–804 (2001). 4. Bajor, A., Tornblom, H., Rudling, M., Ung, K. A. & Simren, M. Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS. Gut http://dx.doi.org/ 10.1136/gutjnl-2013-305965. 5. Krogsgaard, L. R., Engsbro, A. L., Stensvold, C. R., Nielsen, H. V. & Bytzer, P. The prevalence of intestinal parasites is not greater among individuals with irritable bowel syndrome: a population-based case–control study. Clin. Gastroenterol. Hepatol. http:// dx.doi.org/10.1016/j.cgh.2014.07.065. 6. Spiegel, B. M. The burden of IBS: looking at metrics. Curr. Gastroenterol. Rep. 11, 265–269 (2009). 7. Chang, M. H. et al. Faecal calprotectin as a novel biomarker for differentiating between inflammatory bowel disease and irritable bowel syndrome. Mol. Med. Rep. 10, 522–526 (2014). 8. Koh, S. J. et al. Psychosocial stress in nurses with shift work schedule is associated with functional gastrointestinal disorders. J. Neurogastroenterol. Motil. 20, 516–522 (2014). 9. Thaiss, C. A. et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostas. Cell 159, 1–16 (2014). 10. Halmos, E. P. et al. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut http://dx.doi.org/ 10.1136/gutjnl-2014-307264.

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IBS in 2014: Developments in pathophysiology, diagnosis and management.

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