Irritable Bowel Syndrome

Dr John McLaughlin PhD MRCP, GI Sciences, University of Manchester

Powerpoint File

Honorary Consultant Gastroenterologist, Salford Royal Hospitals Trust

Irritable bowel syndrome (IBS) clusters a consistent group of gastrointestinal symptoms such as pain or bloating, necessarily associated with defaecatory abnormalities, and occuring in the absence of recognised organic disease1.

Some 70% of an unselected population will report at least one gut-centred symptom, while about 3-20% satisfy agreed IBS criteria Almost 50% of patients referred to medical gastroenterologists have no organic disease to account for their symptoms, and many of these are given a diagnostic label of IBS. It is important not to be misled into believing that a syndrome of symptoms can be equated to a singular disease entity simply by experts giving it a consensus name. The Rome II criteria2 are currently most widely used for IBS: these are a handy tool for streamlining recruitment of similar patients into multi-centre clinical trials, but are of little real utility in clinical practice. For example, a patient passing 5 urgent watery stools daily cannot have the same pathophysiology as a patient forcing hard pellety stool twice a week, yet both can satisfy the criteria for ‘IBS’. There is an association with co-existent functional dyspepsia, chronic fatigue, fibromyalgia, bladder and gynaecological symptoms, and back pain. Attempts to define pathophysiological abnormalities have been disappointing3 eg no consistent abnormalities have been identified in gut motility studies.

Indeed it is not yet clear whether the problem is truly enteric, or lies in aberrant processing within the central nervous system. Herein lies the role of psychological factors, clearly prominent in driving worried individuals to seek secondary care yet not necessarily causative of the symptoms themselves1. The model currently advanced is of neurogastroenterological dysfunction, potentially originating in several loci within the brain-gut axis3. The two major possibilities are (peripheral) visceral hypersensitivity or (central) hypervigilance. These concepts may help unify IBS with the other ‘functional’ symptom complexes listed above, centred both within and outside the gut.
Peripherally, there is growing evidence for molecular/cellular abnormalities and enhanced responsiveness in neural, immune and enteroendocrine circuits4-7. Post-inflammatory IBS of defined onset eg Campylobacter may be a useful study model4, and we have demonstrated that similar epithelial changes can be induced in animal models of infection8. Disordered barrier function has also been implicated by inference from permeability studies3,4.

Given the lack of a singular cause, it is therefore unsurprising that the evidence for benefit of current therapies is weak or absent. Recent market-driven Pharma interest has focused on serotoninergic pathways, endogenous opioids, and regulatory peptides such as CCK and corticotrophin releasing hormone1,9. More objective isolated outcome measures such as bowel frequency can be demonstrably shifted in subgroup analyses from drug trials: however, these outcomes may poorly correspond to key symptoms such as pain or bloating. The usual standard trials against placebo are less apt than the generally missing trials eg against simple laxatives. Understanding the causative factors and pathobiology of these common unexplained symptoms, leading to more accurate biological and psychological subclassification of patients, will be necessary before currently blind pharmacotherapy can be significantly advanced.

1. McLaughlin, JT. Irritable Bowel Syndrome. Medicine 2003; 31:88-89
2. Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead
WE, eds. ROME II. The functional gastrointestinal disorders.
Diagnosis, pathophysiology and treatment: a multinational consensus.
2nd ed. McLean, VA: Degnon Associates, 2000.
3. Mayer EA, Collins, SM. Evolving Pathophysiologic Models of Functional Gastrointestinal Disorders Gastroenterology 2002;122:2032–2048
4. Spiller RC et al Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut. 2000 Dec;47(6):804-11.
5. Stanghellini BG et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004; 126:693-702
6. Chadwick VS et al. Activation of the mucosal immune system in IBS. Gastroenterology 2002; 122:1778-1783
7. Tornblom H et al Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology. 2002;123:1972-9.
8. Leslie, FC, McDermott, J, Kazmi, S, Grencis, RK, Thompson, DG, McLaughlin, J. Small intestinal inflammation is associated with increased EEC numbers and hypophagia.Gut 2003; 52(S1):A15
9. Spiller, RC. Treatment of IBS. Curr Treat Options Gastroenterol. 2003;6:329-337

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