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causes of ibs - part one

There are a number of different theories regarding the cause of IBS, and I have outlined the main theories below. Although I've separated them out into different categories for easy reading, in reality there may well be intrinsic links between the theories. I've included information from a number of clinical studies on this page. Whenever a clinical study is mentioned, it's presented as a bullet point, and in each case I give the title of the study, the names of the researchers, the name of the journal that published the study, and a link to a Pubmed summary of the study.

Brain-gut dysfunction

Although the understanding of what causes IBS is still in its infancy, one of the things that most experts agree on is that IBS patients suffer from something called 'visceral sensitivity'. This is basically a fancy term for the fact that IBS sufferers have more sensitive intestines than healthy people, and so contractions of the intestines that wouldn't bother most people are felt by IBS patients as painful - and contractions that are particularly severe, involving diarrhea for example, can be agonizing.

This heightened sensitivity is an accepted part of IBS theory because it has been shown in several clinical studies that IBS sufferers actually process gut stimuli in a different way to non-sufferers, leaving us with a lower threshold for pain.

This is categorically not an invitation for lots of people to start beating IBS sufferers over the head with a big stick saying 'Yes, I knew you were all just wimps. Get a grip'. We don't, of course, have any control over our pain thresholds, and indeed the studies which show that we process gut stimuli in a different way are proof of this - I don't know about you but I don't have much conscious control over my anterior cingulate cortex.

• Regional Cerebral Activity in Normal and Pathological Perception of Visceral Pain Gastroenterology 1997
  
  The researchers looked at the correlation between rectal pressure, cerebral blood flow, and the perception of intestinal pain. Twelve subjects were studied, six of whom suffered from IBS.
  
  In healthy subjects, perception of pain was associated with activity with the anterior cingulate cortex or ACC, but the ACC did not respond to non-painful stimuli. However, in IBS patients, the ACC failed to respond to the same types of stimuli, but they did show a response within the left prefrontal cortex.
  
  Conclusion: Patients with IBS show an aberrant brain activation pattern both during noxious rectal distention and during the anticipation of rectal pain. Pubmed article: Silverman DH, Munakata JA, Ennes H, Mandelkern MA, Hoh CK, Mayer EA

What this aberrant brain activation shows is that we IBS people are processing our gut stimuli in a different way to non-sufferers. This is pretty interesting stuff, but what it doesn't tell us is what is causing the heightened sensitivity. So, researchers have started to investigate what is called the 'brain-gut dysfunction', and indeed some of the possible causes of IBS listed below are being examined for the effect they could have on the brain-gut axis.

Here's a paper which sums up the possible role of the brain-gut axis in IBS (the word 'pathogenesis' just means the origination of a disorder, ie: the cause).

• Brain Research in Functional Gastrointestinal Disorders (A Review) Journal of Clinical Gastroenterology 2002
  
  The current understanding is that functional gastrointestinal disorders result from dysregulation of the bidirectional communication between the gut and the brain (ie: the brain-gut axis), modulated by various psychosocial and environmental factors.
  
  Studies have shown that visceral/gut sensation involves activation of several brain regions that are associated with various brain functions, including sensation, cognition, and affect. Brain research suggests that patients with irritable bowel syndrome differ from healthy subjects in the way that their brain responds to visceral (eg: rectal) distention.
  
  Conclusion: These studies suggest that alteration in brain processes involving perception and affective responses might be key factors in the pathogenesis of functional gastrointestinal symptoms. Pubmed article: Ringel Y

Low-grade inflammation

One of the reasons why IBS has been considered a rather mysterious disorder in the past is because tests such as colonoscopies and blood tests would always come back negative, and no visible sign of a problem could be found. This was in direct contrast with other disorders such as inflammatory bowel disease, where the inflammation of the intestines could be seen during a colonoscopy.

Recently, however, studies have begun to find that although there is no inflammation present that is visible to the naked eye, IBS patients may display low-grade inflammation which can be detected through biopsies and microscopic studies.

• Activation of the mucosal immune system in irritable bowel syndrome Gastroenterology 2002
  
  This study examined biopsies from 77 IBS sufferers and 28 non-sufferers.
  
  Conclusion: It was found that 31 of the IBS patients showed some non-specific microscopic inflammation and also had increased numbers of white blood cells and mast cells. Pubmed article: Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, Wilson I


• Post-infectious Irritable Bowel Syndrome (A Review) Current Opinion in Gastroenterology 2006
  
  Recent studies have overthrown the dogma that irritable bowel syndrome is characterized by no abnormality of structure by demonstrating low-grade lymphocytic infiltration in the gut mucosa, increased permeability and increases in other inflammatory components including enterochromaffin and mast cells.
  
  Furthermore, increased inflammatory cytokines in both mucosa and blood have been demonstrated in irritable bowel syndrome. While steroid treatment has proved ineffective, preliminary studies with probiotics exerting an anti-inflammatory effect have shown benefit.
  
  Conclusion: The study of post-infectious irritable bowel syndrome has revealed the importance of low-grade inflammation in causing irritable bowel syndrome symptoms. It has suggested novel approaches to irritable bowel syndrome including studies of serotonin and histamine metabolism which may be relevant to other subtypes of the disease. Pubmed article: Robin Spiller; Eugene Campbell

Mast cells

Mast cells are another area where physical differences have been found between IBS sufferers and healthy people. Mast cells have a number of roles within the body, including influencing smooth muscle function - and so mast cells could be implicated in the visceral sensitivity which characterizes IBS.

• Increased Mast Cells in the Irritable Bowel Syndrome Neurogastroenterology Motility 2000
  
  Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls.'
  
  The researchers used biopsies to test the intestines of 14 IBS patients, and found that the density of mast cells was significantly higher in the cecum of IBS patients than in healthy control patients, but levels of mast cells in other tested areas such as the ascending colon, descending colon and rectum were similar between test and control groups.
  
  Conclusion: 'The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS. Pubmed article: O'Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, O'Morain CA


• Mast Cells: A Possible Link Between Psychological Stress, Enteric Infection, Food Allergy and Gut Hypersensitivity in the Irritable Bowel Syndrome, Journal of Gastroenterology and Hepatology 1998
  
  'Intestinal mast cell activation (degranulation), which results from previous enteric infection and/or intestinal allergy, may play a central role in the gut hypersensitivity in both motor response and visceral perception in the irritable bowel syndrome.This occurs through various mediators acting on enteric neurons and smooth muscle cells.
  
  Conclusion: Psychological stress may trigger this sensitive alarm system via the brain-gut axis. Pubmed article: Gui XY


• Functional gastrointestinal disorders and mast cells: implications for therapy Neurogastroenterology Motility 2006
  
  Mast cells (MCs) are immunocytes widely distributed throughout the gastrointestinal tract. Several stimuli (eg: allergens, neuropeptides and stress) lead to MC activation with consequent mediator release (e.g. histamine, tryptase and prostanoids). The MC mediators interact with nerves supplying the gut leading to altered gut physiology and increased sensory perception.
  
  The intestinal mucosa of irritable bowel syndrome patients contains on average an increased number of MCs. These cells release an increased amount of mediators in close vicinity to mucosal innervation. The MC activation and their close proximity to nerve fibers is correlated with the severity of perceived abdominal painful sensations.
  
  Conclusion: These data provide a strong basis for considering mast cells as important participants in visceral hypersensitivity and pain perception in irritable bowel syndrome. Inhibition of MC function may ameliorate irritable bowel symptoms. Pubmed article: Barbara G, Stanghellini V, De Giorgio R, Corinaldesi R

Bacterial causes

There are many IBS sufferers who can trace the onset of their symptoms back to the use of antibiotics or a stomach upset, and one bacterial theory of IBS suggests that the symptoms are the results of an imbalance between the 'good' and 'bad' bacteria within the gut. This theory is supported by studies that have shown the strong negative influence that antibiotics can have on bowel symptoms, as well as the positive influence that probiotics can have.

• Antibiotic use, childhood affluence and irritable bowel syndrome European Journal of Gastroenterology and Hepatology
  
  This study looked at a possible link between antibiotic use and the development of IBS. The researchers interviewed 421 subjects who were attending a general health screening, and they found 48 people with symptoms of IBS. They found that antibiotic use was strongly related to the presence of IBS.
  
  Conclusion: Antibiotic use is associated with IBS.Pubmed article: Mendall MA, Kumar D



• Antibiotics increase functional abdominal symptoms American Journal of Gastroenterology 2002
  
  The researchers looked at patients who had visited their doctor with heath complaints that were not gastrointestinal, but who had been prescribed antibiotics. These patients were monitored over a four-month period, and compared against a control group who had not received antibiotics.
  
  The researchers found that 48% of patients who had taken the antibiotics developed one or more bowel symptoms, compared to 22% of the patients who did not receive antibiotics. They also found that 24% of the patients who had taken antibiotics developed two or more bowel symptoms, compared to only 6% of the control patients.
  
  Conclusion: Subjects who are given a course of antibiotics are more than three times as likely to report more bowel symptoms four months later than controls. Pubmed article: Maxwell PR, Rink E, Kumar D, Mendall MA



• Use of diet and probiotic therapy in the irritable bowel syndrome: analysis of the literature Journal of Clinical Gastroenterology 2005
  
  This was a review of six previous studies of irritable bowel and the use of probiotics.
  
  Conclusion: Studies generally showed decreased IBS symptoms when probiotics are used, although more research was necessary to fully evaluate probiotics. Pubmed article: Floch MH

Another bacterial theory suggests that IBS is not caused by an imbalance between good and bad bacteria, but by an overgrowth of bacteria in the wrong place within the gut. Dr Mark Pimentel of Cedars-Sinai Medical Center has pioneered the theory of Small Intestinal Bacterial Overgrowth (SIBO), which states that IBS symptoms are caused by gas-producing bacteria within the small intestine. By testing patients for the presence of bacteria with a simple breath test, and then treating these bacteria with antibiotics and diet therapy, the IBS symptoms can be eliminated.

Clinical trials have already shown good results for patients who follow this approach. One of the most interesting aspects of this theory is that it offers a possible explanation for fact that some IBS sufferers are diarrhea-predominant, and some are constipation-predominant (various types of bacteria emit different gases and therefore cause different symptoms).

• Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study American Journal of Gastroenterology 2003
  
  A study published in the examined whether antibiotics could reduce IBS symptoms after an abnormal SIBO test. A total of 111 IBS patients took part in the study, and of these, 84% produced an abnormal breath test, compared with 20% in healthy controls.
  
  Patients in the test group were treated with the antibiotic neomycin, and reported a 35% improvement in symptoms, compared to 11.4% improvement in the placebo group. Patients who had received neomycin also reported a bowel normalization of 35.3% compared to 13.9% for the placebo group. If the neomycin was successful in normalizing the results of the breath test there was a 75% improvement in symptoms.
  
  Conclusion: Normalization of the Lactulose breath test with neomycin leads to a significant reduction in IBS symptoms. Pubmed article: Pimentel M, Chow EJ, Lin HC

Go to Causes of IBS (Part Two)

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