Irritable bowel syndrome (IBS) has no single known cause. Several risk factors raise the chance of developing it, and several interacting mechanisms — none proven sufficient on its own — are proposed to explain its symptoms.
Risk factors
The best-accepted risk factor is prior infectious gastroenteritis. After a gut infection the risk of IBS rises several-fold, and the likelihood depends on the organism: it is highest after a protozoal infection, lower after a bacterial one and lowest after a viral one. Within that, a longer or more severe initial infection raises the risk further, as do female sex, younger age, and pre-existing anxiety or depression.
Other factors associated with IBS include pre-existing psychological disorders such as anxiety and depression, a history of physical, sexual or emotional abuse, an affluent childhood environment, food intolerance, a low quality of life and previous antibiotic use.
Pathophysiology
For a long time there was no biochemical, physiological or anatomical change to account for the functional symptoms of IBS. It is now understood as a disorder of the interaction between the gut and the brain, in which several mechanisms act together; each one is a proposed contributor rather than a confirmed cause on its own.
Altered motility
Bowel transit is disturbed in IBS, in opposite directions depending on the subtype: transit is decreased in IBS-C (constipation-predominant) and increased in IBS-D (diarrhoea-predominant). The reflex response to a meal or to distension of the ileum is abnormal too: after infusion of cholecystokinin (CCK), or after distension of the ileum, bowel movement is stimulated much more strongly in healthy controls than in patients with IBS. The pattern of control also differs by subtype: IBS-C is associated with vagal (parasympathetic) dysfunction, and IBS-D with sympathetic dysfunction of the gastrointestinal tract.
Visceral hypersensitivity
Visceral hypersensitivity means the gut senses ordinary events as painful. When a balloon is inflated inside the bowel, more than 60% of patients with IBS report pain, which indicates that they are more aware of gas or food distending the bowel than healthy people are.
Brain–gut interaction and psychological factors
IBS is increasingly understood as a disorder of the gut–brain axis, the two-way signalling between the gut and the central nervous system. Psychological disorders such as anxiety and depression are reported more often in patients with IBS than in healthy people, and a history of sexual, physical or emotional abuse is also more common. The direction of the relationship matters: in more than 50% of patients with a psychological disorder, the gastrointestinal symptoms come first and the psychological changes develop later. The same loop runs through immune signalling — for example, increased inflammation and increased tumour necrosis factor α (TNF-α) can drive anxiety, because TNF has effects in the brain as well as in the immune system.
Low-grade inflammation, immune activation and increased permeability
The healthy gut keeps a controlled, low-grade inflammation where commensal bacteria meet the epithelial immune barrier. In IBS this background is amplified: levels of inflammatory markers such as cytokines, and numbers of inflammatory cells such as mast cells, are higher than in healthy people. The increased mast-cell activity is the main reason the finding matters — it widens the gaps between the intestinal epithelial cells and raises gut permeability.
The intestinal microbiota and SIBO
The composition of the stool and mucosal microbiota differs between healthy people and patients with IBS, and the disturbance is most prominent after an infection. Small intestinal bacterial overgrowth (SIBO) has been proposed as one explanation for IBS symptoms, but its prevalence and importance are uncertain, and breath testing for it is not routinely recommended. Reported shifts include a reduction of lactobacilli with a relative increase in Bacteroides.
Bile acids
Bile salts in the stool can deviate from the normal range in IBS, and the direction follows the subtype: they are usually higher in IBS-D, which speeds colonic transit, and lower in IBS-C.
Gas handling and abdominal accommodation
When gas is infused into the bowel, patients with IBS reach their pain threshold at a lower volume. They also respond abnormally to distension of the abdomen, relaxing the abdominal wall muscles while the diaphragm is contracted against the distended contents — a pattern called abdominal accommodation.
Serotonin (5-HT)
Serotonin (5-HT) is a neurotransmitter stored in the enterochromaffin cells of the gut lining. When it is released, it increases gut motility and stimulates sensory neurons; it is then taken back up by the enterocytes through the serotonin transporter, which stops its action. Both ends of this cycle are reported to be disturbed in IBS: reuptake is reduced in IBS-D, while release is impaired in IBS-C.
Food intolerance and FODMAPs
Food is one of the most commonly reported triggers of symptoms. FODMAPs — fermentable oligosaccharides, disaccharides, monosaccharides and polyols — are short-chain carbohydrates that are poorly absorbed in the small bowel. Because they are osmotically active they draw water into the small intestine, and in the colon they are rapidly fermented by bacteria, producing gas; together these effects distend the bowel and provoke pain and bloating. The gut normally handles a large fluid load — about 10 litres of secretions, from saliva to pancreatic juice, pass through the intestine each day — and most of it is reabsorbed, so the disturbance in IBS appears to lie in how the water and gas are sensed rather than in a failure to absorb them. Insoluble fibre, such as bran, is a recognised trigger that tends to worsen symptoms, whereas soluble fibre is usually tolerated better.