Dr John Wright



The pathophysiology of the irritable bowel syndrome

Dr John P Wright
Updated 15 April 2013

Irritable bowel syndrome (IBS) is one of the commonest diagnoses made by both primary care physicians and gastroenterologists. In order to treat successfully an understanding of the pathophysiology is essential. IBS is defined as chronic abdominal symptoms of bloating, altered bowel habit and cramping pain arising from the colon but with no underlying organic pathology. Recent research, reviewed below, has shown some abnormalities but these remain controversial and their significance uncertain. Intense research into patients with IBS has yielded a variety of findings which can be grouped into dysmotility, visceral hypersensitivity, mucosal inflammation, hereditary causes, enteric bacterial aberrations. dietary and psychosocial factors. These will be reviewed below.

Intestinal dysmotility

Given the nature of IBS symptoms it was to be expected that initial research efforts would concentrate on intestinal motility. Indeed early work revealed that whereas in normal subjects the basic underlying electrical waves traveled through the colon a rate of 6 contractions per minute, patients with irritable bowel had a rate of 3 contractions per minute (1). A complicating observation was that patients under stress with no gastrointestinal symptoms also demonstrated similar motility disturbances (2). It is interesting that patients suffering with anxiety often experience borborygmi more frequently than patients with IBS.

An important physiological abnormality in patients with IBS is impaired intestinal gas evacuation. Patients who complain of bloating and excess gas have been shown to have normal volumes of gas in their bowels but to have a reflex that causes there abdominal muscles to relax while the diaphragm descends to push the abdominal contents forwards giving the classical appearance of abdominal distension so characteristic of patients with IBS. This reflex is common to other mammals in response to intestinal distension (3,4).

Giant peristaltic waves and motility dysfunction have been shown to be associated with cramps in patients with IBS and these are set off with disproportionate ease by intra luminal lipids at physiological concentrations (5). This probably underlies the discomfort patients with IBS suffer after richer meals than normal particularly when eating out in restaurants. Excessive contractions in the recto-sigmoid area after meals have been demonstrated in patients with IBS as well as disturbances of hypersensitivity (6). In the final analysis motility studies in IBS have been plagued by inconsistency. No predominant pattern of motor activity has emerged as a marker for IBS. In spite of this lack of a hypothesis, studies have identified various molecules with symptom alleviating characteristics. Tegaserod (Zelnormâ), now withdrawn, activates 5-HT4 receptors located on neurons of the gastrointestinal tract. It increased gastrointestinal motility in patients with constipation-predominant irritable bowel syndrome (7). A herbal preparation, Iberogast, appears to have a similar useful role in patients with abdominal pain and constipation (8).

Intestinal hypersensitivity

Visceral hypersensitivity has been shown to be integral to a variety of chronic pain syndromes and can affect different sites in the gut (9). The perception of pain from the gastrointestinal tract results from stimulation of various chemoreceptors and mechanoreceptors in the gut wall which in turn transmit signals via afferent neural pathways to the dorsal horn of the spinal cord and on to the brain. These central effects may be blocked. In a fascinating study it was recently shown that oesophageal pain caused by acid perfusion could be blocked centrally with very low doses of Ketamine that did not have any other measurable effect.

A similar central interpretation of visceral pain is thought to apply to the colon (10). In patients with IBS increased rectal discomfort on balloon distension as compared to normal controls is well described (11). In contrast the threshold for somatic pain appears to be elevated. In a study using electrical stimulation IBS patients were again shown to have a higher threshold as compared to controls. Interestingly this hypoalgesia was even greater in patients with concomitant fibromyalgia, suggesting a commonality between these two symptom driven diagnoses (12,13).

Anticipatory factors may also play a part. In experiments where the sigmoid is repeatedly distended increased sensitivity is noticed (14). This is thought to be part of the explanation for symptoms of IBS after transient bowel infections separate from the inflammatory process set up which is discussed below. The Pavlovian dog was the initial example of this mechanism. It is now thought that even intrauterine foetal cramps could establish a pattern of pain recognition that lasts long after birth

A complicating factor in understanding intestinal hypersensitivity is that not all patients with IBS experience hypersensitivity. It appears only in those patients who seek medical attention as it was not found in community based patients (15). This observation suggests that patients seeking medical attention may be different from those who simply experience gastrointestinal symptoms without the need for further reassurance.

Mucosal inflammation

The clinical entity of post infectious IBS has spurred on examination of the mucosa in IBS patients. The reward has been significant increases in inflammatory cells such as neutrophils, lymphocytes and mast cells (16). The cytokines and other neurotransmitters released by these cells may have a local and central affect (17). Persistent irritable bowel symptoms have been noted in approximately 20 to 30 percent of patients after acute bacterial and viral infection. The symptoms experienced by these patients were looser stools with more urgent and frequent defecation and a suggestion of rectal irritability (18,19).

The increase in inflammatory cells following acute Campylobacter enteritis may last for more than a year (20). In a study of the use of prednisone in similar patients neither the cellular infiltrate nor the symptoms resolved on treatment (21). The whole relationship between infectious colitis, microscopic colitis, inflammatory bowel disease and IBS needs to be explored further.

Hereditary causes

It is a frequent clinical observation that the mother of the young woman with IBS also had IBS and often her mother before her. This familial incidence is supported by a study which found that concordance rates for IBS were twice as high in monozygotic compared to dizygotic twins. A confounding observation however was that having a parent with IBS was a greater independent predictor for IBS than having an affected twin (22). Some mothers would argue that IBS is inherited from their children.

Psychosocial factors

It is a general perception that patients with IBS have increased anxiety, depression, phobias, and somatization. They are therefore viewed as neurotic. There is in fact increasing data that the brain-gut axis is real and integral to the condition.

Positron emission tomography imaging has shown that IBS patients light up regions associated with emotional arousal and endogenous pain modulation in response to rectal distension. Controls have greater stimulation of cognitive regions (23, 24).

These patients however do not have a major psychiatric diagnosis. These psychological abnormalities are only found in patients presenting in tertiary medical institutions. Those who do not seek medical attention are indistinguishable psychologically from healthy controls (15).

Intra Luminal Bacterial Happenings

Altered bowel ecology is the current vogue with the proliferation of probiotic products to return the bacterial population towards a perceived normality.

As the ultimate ecological interference, the increasing popular faecal transplant has been studied. A faecal transplant between patients with irritable bowel and mice results in mice with signs of IBS!! (25).

Dietary Factors

While conditions such as lactose intolerance may cause bloating and diarrhoea there is no evidence that they cause IBS. Food sensitivities and allergies appear to play a very small part in IBS(26). A very low carbohydrate diet improves patients with diarrhea predominant IBS although the possibility of underlying celiac disease or other pathology always needs to be considered in these patients (27).

Diet plays little role in the pathophysiology of IBS although it plays a central role in the attempt to normalize bowel function.


While the initiating cause of IBS is unknown, abnormalities of the intestinal physiology are well documented. Although an all-encompassing hypothesis is still lacking, one can deduce that IBS is not a psychological disease and nor is it a dietary disease.

Treatment needs to address the abnormal physiology and underlying anxiety. Diet is all important. A rough (IE nuts and seed) diet with adequate fibre and minimal chemical interference is needed.


  1. Snape WJ Jr; Carlson GM; Cohen S. Colonic myoelectric activity in the irritable bowel syndrome. Gastroenterology 1976 Mar;70(3):326-30.
  2. Latimer P; Sarna S; Campbell D et al. Colonic motor and myoelectrical activity: a comparative study of normal subjects, psychoneurotic patients, and patients with irritable bowel syndrome. Gastroenterology 1981 May;80(5:t 1) p893-901
  3. Lasser RB; Bond JH; Levitt MD. The role of intestinal gas in functional abdominal pain. N Engl J Med 1975 Sep 11;293(11):524-6.
  4. Serra J; Azpiroz F; Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut 2001 Jan;48(1):14-9.
  5. Serra J; Salvioli B; Azpiroz F; Malagelada JR. Lipid-induced intestinal gas retention in irritable bowel syndrome. Gastroenterology 2002 Sep;123(3):700-6.
  6. Jepsen JM; Skoubo-Kristensen E; Elsborg L Rectosigmoid motility response to sham feeding in irritable bowel syndrome. Evidence of a cephalic phase. Scand J Gastroenterol 1989 Jan;24(1):53-6.
  7. Prather CM; Camilleri M; Zinsmeister AR et al. Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology 2000 Mar;118(3):463-8.
  8. Melzer J, Rosch W, Reichling L et al Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther 2004 ;20:1279-87.
  9. Willert RP, Woolf CJ, Hobson AR et al. The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-D-aspartate receptor. Gastroenterology 2004;126:683-692.
  10. Trimble KC; Farouk R; Pryde A et al. Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. Dig Dis Sci 1995 Aug;40(8):1607-13.
  11. Bouin M; Plourde V; Boivin M et al. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology 2002;122:1771-7.
  12. Cook IJ; van Eeden A; Collins SM. Patients with irritable bowel syndrome have greater pain tolerance than normal subjects. Gastroenterology 1987;93:727-33.
  13. Iovino P, Tremolaterra F, Consalvo D et al Perception of electrocutaneous stimuli in irritable bowel syndrome. Am J Gastroenterol. 2006;101:596.
  14. Munakata J; Naliboff B; Harraf F et al. Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome. Gastroenterology 1997 Jan;112(1):55-63.
  15. Whitehead WE; Bosmajian L; Zonderman AB et al. Symptoms of psychologic distress associated with irritable bowel syndrome. Comparison of community and medical clinic samples. Gastroenterology 1988 Sep;95(3):709-14.
  16. Chadwick VS; Chen W; Shu D et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 2002 Jun;122(7):1778-83.
  17. 1Barbara G, Stanghellini V, de Giorgio R et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004;126:693-702.
  18. Neal KR; Hebden J; Spiller R. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients. BMJ 1997 Mar 15;314(7083):779-82.
  19. Zanini B, Ricci C, Bandera F et al Incidence of post-infectious irritable bowel syndrome and functional intestinal disorders following a water-borne viral gastroenteritis outbreak. Am J Gastroenterol. 2012;107:891.
  20. Spiller RC; Jenkins D; Thornley JP 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;47:804-11.
  21. Dunlop SP; Jenkins D; Neal KR et al. Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome. Aliment Pharmacol Ther 2003 Jul 1;18(1):77-84.
  22. Levy RL; Jones KR; Whitehead WE et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology 2001 Oct;121(4):799-804.
  23. Mertz H, Morgan V, Tanner G et al Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention Gastroenterology. 2000;118:842.
  24. Tillisch K, Mayer EA, Labus JS Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology. 2011;140:91-100.
  25. Gecse K, Róka R, Ferrier L et al Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity. Gut. 2008;57:591.
  26. Zwetchkenbaum J, Burakoff R The irritable bowel syndrome and food hypersensitivity.Ann Allergy. 1988;61:47.
  27. Austin GL, Dalton CB, Hu Y et al A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2009;7:706.