Aetiology and pathogenesis

  1. Aetiology and pathogenesis

It is unlikely that there is one underlying factor that explains the pathogensis of IBS, and more likely that it is the outcome of the complex interplay between a number of factors involving the gut and the central nervous system [1].

Post infectious IBS

Between 3.7-36% of patients who have suffered bacterial or viral gastroenteritis will go on to develop IBS [2,3], a recent meta-analysis of published trials reported a sevenfold increased risk of developing IBS after an episode of infectious gastroenteritis [4].
 

Gut bacteria

There are over 1000 species of human gut bacteria and each individual is populated by at least 160 different species, including a core of 18 species present in all humans. The role of these gut bacteria in the pathogenesis of IBS is being increasingly recognised. Research has shown that there are alterations in the bacteria in patients with IBS with lower levels of Lactobacilli and Bifidobacteria [5] and that gut bacteria can be adversely affected by gut infections and gastroenteritis [6].
 

Gut permeability

The lining of the intestine and the mucus that it secretes protect the body from absorbing unwanted molecules as they pass along the gut. However, studies into IBS show that the gut lining in some patients is damaged resulting in unwanted molecules crossing the gut wall into the body and potentially activating the body’s immune system [7,8]. This defect is principally seen in diarrhoea dominant IBS patients and interestingly is most notable in non-post infectious IBS [7].
 

Immune activation

Increased activity of the innate immune system is seen in subgroups of IBS patients [6]. There is some suggestion of immune mast cell involvement, particularly in those with diarrhoea dominant IBS, where allergic type responses may result in the release of inflammatory chemicals in the gut [9,10]. Increased mast cell infiltration has been observed in close proximity to nerve fibres in the colon in IBS patients, which could explain increased levels of pain in these subjects [11]. Some studies speculate as to whether there are subgroups of IBS patients for whom food allergy is responsible for this immune activation [12]. It is also well recognised that patients with food allergy can be incorrectly diagnosed with IBS and it is possible that those with mast cell involvement fall into this category.  However, adult allergy, which predominantly affects the gut, is often non-IgE in nature and therefore will not show up on allergy tests making it difficult to confirm [15]. The adaptive immune system has also been implicated in IBS with raised numbers of T cells being noted in the gut of some IBS patients [13]. However, research is conflicting and more work is needed to look into immune involvement in IBS symptoms.

Stress Factors

Corticotrophin-releasing hormone (CRH) mediates the stress response and has been shown to increase gut motility. It has also been shown to promote inflammation by increasing intestinal permeability in IBS patients. CRH can also alter gut bacteria, gut secretions, sensitivity of the gut wall and the blood flow to the intestine [1]. These effects may go part of the way to explaining why some people find that their symptoms deteriorate during periods of stress. What we don’t yet fully understand however is how significant stress and the body chemicals associated with stress are in the development of IBS as a condition.
 

Food ingestion

Half of IBS patients report deterioration in gut symptoms after eating [1]. Research has shown that patients predominantly seek advice on diet and the role of food in their condition and an inability to refer on for appropriate dietetic input may lead to over restrictive diets and reinforce a vicious cycle of health worry with increased GP visits and demands for more testing and prescriptions (Halpert et al.2007) The 2008 NICE guidance on IBS suggested diet and lifestyle as a first line treatment for IBS. It suggested that if diet was considered a major factor in the symptoms then the patient should be referred to a registered dietitian. In 2015 the NICE guidelines for IBS were updated to include mention of the low FODMAP diet as a form of treatment [19]. 

 

Role of FODMAPs in IBS symptoms

There is increasing evidence that many IBS patients exhibit an intolerance to poorly absorbed carboydrates such as frucose, lactose, polyols, fructans and galacto-oligosaccharides, known commonly as ‘FODMAPs’ [16-18]. These foods can cause fermentation in the gut resulting in gas, wind and bloating in sensitive individuals, while also increasing water delivery into the bowel resulting in loose stools. The low FODMAP diet removes these foods for an 8 week period and then reintroduces them to tolerance. The diet is now widely used within the UK and is recommended by both the UK NICE Guidelines [19] and the British Dietetic Association IBS Guidelines [20].

Both coeliac disease and the more recently recognised condition - non coeliac gluten sensitivity, can exhibit IBS-type symptoms. Benefits of gluten restriction on IBS-type symptoms have been reported [21], however wheat contains high levels of  ‘fructans’  which are a FODMAP.  Therefore  it is plausible that the improvement in symptoms, at least for some individuals, may simply be related to the reduction/exclusion of fructans and not associated with the removal from the diet of the gluten protein.

 

 

References

  1. Hayes PA. Irritable Bowel Syndrome: The Role of Food in Pathogenesis and Management. Gastroenterology & Hepatology  2014;10(3):164-74.
  2. Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology. 2009;136(6):1979-88.
  3. Marshall JK, Thabane M, Garg AX, Clark WF, Moayyedi P, Collins SM. Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery. Gut. 2010;59(5):605-11.
  4. Halvorson HA, Schlett CD, Riddle MS. Postinfectious irritable bowel syndrome--a meta-analysis. Am J Gastroenterol. 2006;101(8):1894-9; quiz 942.
  5. Whelan K. Probiotics and prebiotics in the management of irritable bowel syndrome: a review of recent clinical trials and systematic reviews. Current opinion in clinical nutrition and metabolic care. 2011;14(6):581-7.
  6. Ohman L, Simren M. Intestinal microbiota and its role in irritable bowel syndrome (IBS). Curr Gastroenterol Rep. 2013;15(5):323.
  7. Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol. 2006;101(6):1288-94.
  8. Marshall JK, Thabane M, Garg AX, Clark W, Meddings J, Collins SM, et al. Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Alimentary pharmacology & therapeutics. 2004;20(11-12):1317-22.
  9. Guilarte M, Santos J, de Torres I, Alonso C, Vicario M, Ramos L, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007;56(2):203-9.
  10. Walker MM, Talley NJ, Prabhakar M, Pennaneac'h CJ, Aro P, Ronkainen J, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Alimentary pharmacology & therapeutics. 2009;29(7):765-73.
  11. Ohman L, Simren M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 2010;7(3):163-73.
  12. Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Rocken C, Brasch J, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014;147(5):1012-20 e4.
  13. Ohman L, et al. A controlled study of colonic immune activity and B7 blood T lymphocytes in patients with irritable bowel syndrome. Clinical Gastroenterology & Hepatology. 2005;3:980-6.
  14. Carroccio A, Brusca I, Mansueto P, D'Alcamo A, Barrale M, Soresi M, et al. A comparison between two different in vitro basophil activation tests for gluten- and cow's milk protein sensitivity in irritable bowel syndrome (IBS)-like patients. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2013;51(6):1257-63.
  15. Holgate ST CM, Broide DH, Martinez FD,. Allergy. 4th Edition ed: Elsevier Saunders; 2012.
  16. Staudacher HM, Irving PM, Lomer MC, Whelan K. Mechanisms and efficacy of dietary FODMAP restriction in IBS. Nat Rev Gastroenterol Hepatol. 2014.
  17. Staudacher HM, Lomer MC, Anderson JL, Barrett JS, Muir JG, Irving PM, et al. Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. The Journal of nutrition. 2012;142(8):1510-8.
  18. Shepherd SJ, Lomer MC, Gibson PR. Short-chain carbohydrates and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108(5):707-17.
  19. National Institute for Health and Care Excellence. Irritable bowel syndrome in adults: diagnosis and management of irritable bowel syndrome in primary care. London: NICE; 2015.
  20. McKenzie YA, Alder A, Anderson W, Wills A, Goddard L, Gulia P, et al. British Dietetic Association evidence-based guidelines for the dietary management of irritable bowel syndrome in adults. J Hum Nutr Diet. 2012;25(3):260-74.
  21. Verdu EF, Armstrong D, Murray JA. Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity. Am J Gastroenterol. 2009;104(6):1587-94.