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What Causes Irritable Bowel Syndrome

A syndrome is a collection of symptoms and signs that tend to occur and run together, producing a recognisable ailment. It may have a variety of causes or no definable cause. That’s how it is with the irritable bowel syndrome (IBS). Many different causes have been suggested, but none has fully explained the many features that constitute irritable bowel syndrome. As with other medical syndromes, it’s possible for different aetiologies (causes) to produce the same symptoms. Many diseases arise through a combination of genetic, environmental and sometimes psychological factors, and this is likely to be the case with irritable bowel syndrome.

Any theory that seeks to explain irritable bowel syndrome must explain its key features, and here we will outline some of the explanations that have been proposed for irritable bowel syndrome.


Up to half of people seen in hospital clinics with irritable bowel syndrome will have some form of psychological disturbance such as depression or anxiety. This may mean that psychological problems cause or exacerbate irritable bowel syndrome, but equally it could simply mean that severe irritable bowel syndrome causes or exacerbates psychological problems. Alternatively, the apparent association between psychological problems and irritable bowel syndrome seen in hospital clinics may just be a result of the type of person that family doctors refer.

Both irritable bowel syndrome and psychological problems are common. Understandably, the combination is more difficult to cope with, and people with irritable bowel syndrome who are also depressed or anxious are more likely to consult their family doctor. The family doctor probably refers only about half of his or her patients with irritable bowel syndrome to a hospital gastroenterologist. Not surprisingly, people with psychological problems in addition to irritable bowel syndrome may not respond as well to simple measures or reassurance, so are more likely to be referred for a specialist opinion. Consequently, a large proportion of people who have been referred will have a psychological problem, including depression, anxiety, obsession or even a history of sexual or physical abuse. There is therefore a widespread belief that irritable bowel syndrome has a psychological origin.

But when individuals with irritable bowel syndrome in the general population are examined, they probably have no more psychological problems than do the rest of the general population. It is perfectly understandable that people with psychological problems, stress or anxiety are more likely to seek medical attention. Moreover, stress will make any illness worse. So although irritable bowel syndrome is not primarily a psychological disorder, it does have psychological components, which should not be ignored and which can be treated so that individuals with irritable bowel syndrome can gain control over their condition.

So some people with irritable bowel syndrome have psychological problems. What does this mean for me?

The primary cause of irritable bowel syndrome may not be a psychological illness. Yet there is often an important psychological element that exacerbates and prolongs the problems and makes the symptoms more difficult to deal with. You should consider whether you have any problems or stresses that might be associated with your irritable bowel syndrome symptoms.



What is Candida?

There are three major groups of fungi: moulds, yeasts and mushrooms. Candida is a yeast that exists as a one-celled organism somewhat larger than a bacterium. Like other yeasts, Candidais able to ferment carbohydrates to alcohol – just like yeasts do in beer-making.

So am I likely to have Candida living in my body?

Candida can be cultured from the faeces in up to 80% of healthy adults. It is regarded as part of the normal flora (the bacteria usually present) of the skin, mouth, intestine and vagina.

DoesCandida cause disease?

The number of Candidaorganisms is usually controlled by competition with the bacteria already present. Following treatment with antibiotics, these bacteria decrease in number and the number of Candida organisms increases. This can show up as the condition called thrush.

Thrush appears as whitish, velvety plaques in the mouth and on the tongue, or in and around the vagina. Under this whitish material is red tissue that may bleed. The lesions can slowly increase in both number and size.Treatment that suppresses the immune system with corticosteroids can also be complicated by thrush. Treatment for Candida is usually straightforward, with nystatin or other anti fungal drugs.

A friend mentioned ‘Candida syndrome’ to me. What is this?

The idea of the Candida syndrome was suggested and popularised by William Crook in his book The Yeast Connection. It has excited much attention in the popular press but very little interest in academic circles. Other names given to this presumed condition include Candida-related complex, polysystemic candidiasis and chronic candidiasis.

The theory goes as follows. The components of our modern lifestyle, including antibiotics, oral contraceptives and diets rich in yeast-containing foods or readily utilisable carbohydrates, mean that when Candida colonises a person’s intestine, it starts to overgrow. This overgrowth results in a variety of symptoms, for example chronic fatigue, anxiety and depression, headaches and respiratory symptoms, as well as an irritable bowel.

Can Candida syndrome be treated?

Yes. Treatment involves long-term therapy with antifungal agents at increasing doses until the symptoms resolve. Oral (by mouth) as well as vaginal nystatin is recommended. Other potent antifungal medicines such as ketoconazole have also been used. Modifying the diet, including restricting sugar and other simple carbohydrates, is used to limit the nutrients that the Candidaneeds.

But is there any evidence that Candida syndrome actually exists?

There are a number of small scientific trials of treatment for Candida that show an improvement in symptoms such as diarrhoea and flatulence, but these are difficult to interpret as they did not include any controls. (Because some conditions get better without specific treatment, and because people sometimes get better simply because they ‘believe’ in the treatment they are getting, any treatment must be compared against another treatment, usually a placebo – an inert substance given as a medicine for its suggestive effect – to know whether it really works. In scientific studies, the ‘other’ treatment is called the control. Studies without controls are of limited value because we cannot know whether the person’s condition has improved because of the treatment, because it was going to improve anyway, or because the person believed it was going to improve.)

In one trial, nystatin was used to treat women with recurring vaginal thrush and many other symptoms consistent with Candida syndrome. The treatment cured the thrush but had no effect on the other symptoms, implying that these ‘other’ symptoms had nothing to do with the Candidainfection. Similarly, a study published in the prestigious New England Journal of Medicine concluded that when women presumed to have candidiasis hypersensitivity syndrome took nystatin, their bodily and psychological symptoms did not improve significantly more than they did with a placebo (a dummy treatment). Treatment with nystatin therefore appears to be unwarranted and ineffective for irritable bowel syndrome or chronic fatigue-type symptoms.

Should I try nystatin anyway? What have I got to lose?

Nystatin is relatively inexpensive and safe. It can cause gastrointestinal side effects such as nausea, vomiting and diarrhoea, and occasional allergic reactions. More potent antifungal drugs such as fluconazole are much more expensive and more likely to have side effects. Moreover, most ‘Candida therapists’ also recommend a diet low in sugar and simple carbohydrates to reduce the proliferation of Candidain the gut, along with the nystatin; they tend too to suggest various supplements and probiotics to enhance the growth of the natural bacteria in the gut.

The more you look into it, the more complicated and expensive the treatment for this so-called syndrome becomes. The proponents of these treatments employ an evangelist approach, and if you believe them you may well benefit from a ‘placebo response’. As the placebo response can last for 3 months, this may be worthwhile for you, but I suggest you direct your energy instead towards treatments that have a more scientific basis.

Why are doctors so sceptical of the Candida syndrome as a cause of irritable bowel syndrome?

Both hospital doctors and family doctors see Candida infections fairly frequently, but we don’t associate them with irritable bowel syndrome. Nor do we notice any improvement in pre-existing irritable bowel syndrome if an incidental Candida infection is treated.

Overgrowth of Candida occurs in the mouth or the vagina of perfectly healthy people. It is unpleasant but easily treated. More serious infections with Candida affecting the lungs, oesophagus, liver, blood and other organs are not unusual in people with a weak immune system. Some of these patients will have irritable bowel syndrome – because it is a common condition. In my experience, however, they do not complain of new or more severe irritable bowel syndrome symptoms in association with an obvious overgrowth of Candida. Moreover, although powerful antifungal treatment usually resolves their Candida overgrowth, the irritable bowel syndrome remains.



What is small bowel bacterial overgrowth?

This is a syndrome in which excessive numbers of bacteria in the small bowel interfere with the digestion and absorption of the food, causing diarrhoea. There may also be bloating, wind and weight loss.

The small bowel, where most of our digestion and absorption takes place, is normally almost sterile. It harbours very few bacteria. By contrast, the large bowel is full of bacteria, so that half the content of the stool is made up of bacteria!

There are a number of mechanisms that keep the small bowel free of bacteria. Acid in the stomach kills most of the bacteria that we ingest with our food. The continuous, rapid movement through the small bowel prevents stagnant pools of nutrients where bacteria could breed, and clears away any bacteria that have migrated up from the large bowel. There is also a valve between the small bowel and the large bowel – the ileocaecal valve – that limits backflow.

But these mechanisms may fail, allowing bacteria to enter and multiply within the small bowel. Surprisingly, the bacteria do not actually invade the body from the small bowel, so there are no symptoms of infection. People with small bowel bacterial overgrowth do not usually feel unwell and do not have a fever.They usually come to the doctor with diarrhoea, which can be watery or fatty, and they may just feel that they have an irritable bowel.

Who gets small bowel bacterial overgrowth?

Anyone can get this disorder, but some people are more likely to. Older people produce less acid to sterilise their food, their immune system may be weaker and the movement in their small bowel may not be as co-ordinated. In those who have diabetes, those who have had surgery on their small bowel and those who have nerve damage, the movement of the small bowel may be abnormal, leading to stagnation, which allows bacteria to multiply.

Is small bowel bacterial overgrowth likely to have caused my irritable bowel syndrome?

The symptoms of small bowel bacterial overgrowth can be identical to those of irritable bowel syndrome, particularly diarrhoea-predominant irritable bowel syndrome. Bloating and diarrhoea are prominent in both syndromes.

One American study of 111 patients with irritable bowel syndrome found evidence of small bowel bacterial overgrowth in 93 (84%) of the patients. Half the patients were treated with an antibiotic and half with a placebo (a dummy medicine). About a third (35%) of the patients receiving the antibiotic improved, compared with 11% of those who had received the placebo. Although this study has not been repeated, it does suggest that at least a proportion of patients with irritable bowel syndrome have small bowel bacterial overgrowth and will respond to treatment with antibiotics.

Does this theory have any limitations as an explanation for irritable bowel syndrome?

It is difficult to understand how small bowel bacterial overgrowth can cause constipation as well as diarrhoea. It has been suggested that some patients have bacteria that produce methane gas, and that the methane may slow the bowel down. Evidence for this effect of methane is sparse at present, so the explanation is unconvincing. Moreover, most people with irritable bowel syndrome have pain as a significant component of their symptoms, whereas most patients with small bowel bacterial overgrowth do not have pain, or if they do, it is not a major feature. Furthermore, small bowel bacterial overgrowth affects men and women equally, whereas irritable bowel syndrome is probably far more common in women.

It is unlikely therefore that this condition explains irritable bowel syndrome. But it may be part of the problem in people with irritable bowel syndrome who have predominant diarrhoea. I frequently treat patients with otherwise unexplained diarrhoea and bloating with antibiotics. In elderly patients, those with diabetes or those who have had surgery on their bowel or stomach, this is often the first therapeutic approach. And a proportion of patients do show a benefit, making the treatment worthwhile.

What does small bowel bacterial overgrowth mean for me? Should I ask my doctor for an antibiotic?

If your main problem is diarrhoea, and if it cannot be easily controlled by low doses of loperamide or similar medications that slow the bowel down, then small bowel bacterial overgrowth is possible. It is particularly common in those with diabetes, people who have had abdominal surgery and the elderly. In such circumstances, it is reasonable to ask your doctor for a course of an antibiotic such as metronidazole.



Is it possible to eliminate the symptoms of irritable bowel syndrome by avoiding specific foods?

A large proportion of people with irritable bowel syndrome believe their symptoms are an adverse reaction to food and might like to try this approach.

It is undeniable that eating certain foods increases the severity of symptoms for many people. What is not clear is whether the food causes the symptoms or just exacerbates them. Does food allergy and intolerance cause irritable bowel syndrome, or are these different problems with exactly the same symptoms? Is it possible to eliminate the symptoms of irritable bowel syndrome simply by avoiding certain foods? – the question remains controversial.

Reactions that are classed as allergic are caused by a response of the immune system to a specific foreign (that is, something that is not part of the body) protein. Intolerance, however, does not happen through the immune system. The mechanisms of intolerance to some foods, such as lactose, are well worked out. For other foods, such as wheat, they are not. I expect too that other intolerances are still waiting to be discovered.

Although some people with irritable bowel syndrome symptoms can gain enormous benefit from avoiding certain foods such as dairy or wheat products, others struggle with food diaries and different diets without any results. They discover after much effort that their response to differrent foods is too inconsistent to draw any conclusions.

To guide individuals on which foods to avoid, a more recent approach has involved identifying a particular type of antibody, called IgG antibody, to specific foods. These IgG antibodies circulate in the blood and help to protect us against bacterial and viral infections. They represent an immune reaction to a current or previous invading organism. The assumption is that if an IgG antibody to a food exists in someone’s blood, the person may be allergic to that food. A diet avoiding all the foods to which a person has IgG anti-bodies would logically, therefore, eliminate any symptoms arising from food allergies.

But this is a controversial theory because it is IgEantibodies that mediate allergy, and the presence of IgG antibodies to food has not previously been thought of as significant. Moreover, people can have IgG antibodies to many different foods, and a diet designed to eliminate all these foods is likely to be difficult to follow and may not be nutritionally balanced. Despite that, a recent study showed that, of the people who managed to stick to such individualised diets, 50% experienced a significant improvement in their symptoms.

What are the limitations of food allergy and intolerance as an explanation for irritable bowel syndrome?

Most allergic or intolerant reactions are associated with diarrhoea rather than constipation, and at least a third of people with irritable bowel syndrome have predominant constipation. Food allergy does not address the variability in symptoms either between people or in the same person over time. Nor does it address the psychological aspects of irritable bowel syndrome and its relationship to stress.

So what does it mean for me? Is it worth avoiding certain foods?

A dietary approach will work for some people, some of the time, to a certain extent. Certainly, if you discover specific foods that consistently cause you problems, you can avoid them, or decide to eat them despite the symptoms. But you need to be aware that some people are drawn into investing a lot of time and effort in trying a dietary approach to irritable bowel syndrome. They can become a little obsessed with avoiding food that might have a detrimental effect on their health in general and on their personal relationships.

There are dietary approaches that are worth trying, but if they fail to produce significant benefit, it is better to accept that the symptoms reflect the reaction of the gut to foods in general rather than specific items in the diet. We should probably agree with the American author Mark Twain: ‘Eat what you like, and let the food fight it out inside.’



I’ve got irritable bowel syndrome. Does this mean that my bowel is inflamed?

Pathologists examining samples of tissue (biopsy specimens) taken from the bowel are unable to differentiate between biopsies from people with and without irritable bowel syndrome. Even the ‘healthy’ bowel is in a constant state of mild inflammation as the immune system battles to control the organisms that normally live in the gut. There may be no obvious extra gut inflammation in those who have irritable bowel syndrome, but this does not rule out an increase, too small to be seen under the microscope, in inflammatory cells that may start or contribute to the problem.

Do anti-inflammatory treatments work in irritable bowel syndrome? Should I try aspirin, ibuprofen or even steroids?

The treatments that we use to control excess inflammation in inflammatory bowel disease (ulcerative colitis and Crohn’s disease) do not improve irritable bowel syndrome. Corticosteroids can initially cause a feeling of well-being in anyone who takes them, but other than that they are no help in irritable bowel syndrome. Preparations of a medicine called mesalazine (brand names, for example, Asacol, Salofalk and Pentasa) which is used for inflammatory bowel disease are completely ineffective in irritable bowel syndrome. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and diclofenac are very effective at controlling pain in the joints and inflamed soft tissues but are useless for irritable bowel syndrome.

My irritable bowel syndrome started after an infection. Does this make a difference?

About 10% of patients with irritable bowel syndrome date the start of their problem to a bout of infective gastroenteritis. Infection with an organism called Campylobacteris particularly associated with subsequent irritable bowel syndrome, usually diarrhoea predominant. In these people, there has been shown to be an excess of a type of white blood cell called a T-lymphocyte in the gut wall, which indicates persisting inflammation. This inflammation is likely to be associated with the production of chemical messengers such as prostaglandins and serotonin, which will increase intestinal secretions and muscular contraction; this then leads to diarrhoea. They may also increase the sensitivity of the bowel to stretching, causing pain.

Is it possible for a previous, unidentified infection to have caused my irritable bowel syndrome?

It is possible for a previous, unidentified infection to change the character of the immune system in the gut. Our current methods may not be sensitive enough to detect changes in the immune system that might contribute to irritable bowel syndrome symptoms. So the statement that only 10% of irritable bowel syndrome arises after an infection may be an under estimate.

Could a change in the type of bacteria that inhabit the bowel result in symptoms of irritable bowel syndrome?

Some supporters of the inflammation theory of irritable bowel syndrome suggest that a change in the gut flora (the bacteria that inhabit the bowel), arising after infection or after treatment with antibiotics, may be important. More harmful bacteria may increase in number, and the immune response to this may lead to symptoms. Indeed, some irritable bowel syndrome patients associate the start of their problem to treatment with anti biotics.

Is this where probiotics come in?

Probiotics are preparations of living organisms that are thought to be beneficial to health. They are bacteria such as Lactobacillus and bifidobacteria; when ingested in sufficient numbers, these manage to survive the upper gut to populate the large bowel. They may be beneficial by producing substances that increase the acidity of the large bowel so that it becomes a less appealing environment for more harmful bacteria. Moreover, they may help to stop harmful bacteria getting into the gut wall simply by their physical presence. Treatment with probiotics is in its early days. A few studies have shown some benefit in irritable bowel syndrome. Probiotics are commercially available in health food stores, and the idea of treating irritable bowel syndrome with probiotics is attractive and generates great interest. However, there isn’t yet enough clinical evidence to enable clear guidelines to be written. Large, well-designed, controlled clinical trials using specific probiotics are warranted.

How does gut inflammation fail to explain the features of irritable bowel syndrome?

The inflammatory disorders of the intestine that we know about, such as ulcerative colitis and infections such as Campylobacter enteritis, almost always cause diarrhoea. But constipation is fre quently a feature of irritable bowel syndrome, and even people with diarrhoea-predominant irritable bowel syndrome may have periods of constipation. Moreover, most inflammatory disorders respond to corticosteroids – often dramatically – whereas irritable bowel syndrome does not. Gut infections are usually self-limiting and do not recur without a repeated exposure. By contrast, irritable bowel syndrome will wax and wane in severity and goes on and on, or recurs for no apparent reason. Finally, in inflammatory disorders in general, the severity of the symptoms is closely related to the severity of inflammation that we find in the affected organ. In irritable bowel syndrome, however, we can see severe symptoms with minimal, if any, inflammation.

So is the gut inflamed in irritable bowel syndrome or not? What are the implications for me?

We are not yet sure. The gut immune system may be altered in subtle ways that we cannot currently detect with any reliability. The current anti-inflammatory treatments that we use to suppress the immune system do not work for irritable bowel syndrome. It may be that, as our understanding of the role of the immune system in irritable bowel syndrome increases, new treatments will emerge. Probiotics might be the precursors of these treatments.



Visceral hypersensitivity is a feature in most patients with irritable bowel syndrome.

What is meant by ‘visceral hypersensitivity’?

The word ‘visceral’ refers to the internal organs of the body, especially the intestine, as opposed to the skin, muscles and bone. ‘Hypersensitivity’ means an abnormally excessive response to normal stimuli. The concept of visceral hypersensitivity evolved in the 1980s to explain how people can get gastrointestinal symptoms without any apparent abnormality in the structure or function of their intestine.

We have sensory organs monitoring every part of our body, and most of these never generate any conscious perceptions. Most of the sensory signals play a role in the automatic regulation of digestion, and usually the only signals that are perceived consciously are those which require a response, for example a desire to defecate. The brain has mechanisms that prevent the vast majority of signals from our internal organs from reaching consciousness. It seems, however, that this mechanism may not work quite as well in some people. The result is visceral hypersensitivity.

This means that people with irritable bowel syndrome are more sensitive than usual to events occurring within their intestine. These ‘events’ may simply be the normal contraction and relaxation of the bowel wall, or the normal exposure or reaction to food.

Does this problem only affect the organs inside the body?

It is not unusual to have odd sensations from various parts of the body.You may feel that your hand or your face is swollen or hot, or just different. You will then examine the offending part, feel it, look in the mirror and so on …. If this examination is entirely unremarkable, you will be reassured and most likely forget about the odd sensation. Unfortunately, when we get odd sensations from the inside, we cannot check them out as easily, so they are more difficult to ignore. The anxiety we then feel may make us even more aware of sensations arising internally, which amplifies them still further.

So if I’ve got irritable bowel syndrome, am I likely to have visceral hypersensitivity?

Visceral hypersensitivity is one of the most consistent findings in research studies on irritable bowel syndrome.These studies mostly involve inflating a balloon in the rectum or lower bowel to determine the pressure or volume at which discomfort or pain is felt. Most people with irritable bowel syndrome report discomfort or pain at significantly lower pressures or volumes, indicating that the bowel is more sensitive to stretching and pressure in irritable bowel syndrome.

Do people with irritable bowel syndrome have a lower pain threshold? Are they just more sensitive to pain?

No, people with irritable bowel syndrome are not oversensitive. Pain thresholds are measured with graded electric shocks to the skin and are quite normal in people with irritable bowel syndrome, even though they can be shown to have visceral sensitivity affecting the large bowel, the small bowel and even the oesophagus.

How and why, then, does visceral hypersensitivity happen?

There are sensors that respond to stretching, pressure or various chemicals located throughout the body, and report back to the brain. Most of the signals that these sensors generate never reach consciousness. The strength of the signal generated from a stimulus, such as increased pressure in a particular part of bowel, depends on a number of factors. Clearly, the stronger the stimulus, the greater the signal, but the strength of the signal also depends on the number of active sensors and their sensitivity to the stimulus. Once the signal has been generated, it travels to the spinal cord, where it is altered. It may be either amplified or de-amplified. Nerve pathways from the brain also descend to the spinal cord and alter sensory transmission still further. Once the signal has reached the brain, it is changed yet again by nerve pathways from the brain‘s emotional centres. Thus, the increased pain signal that indicates visceral hypersensitivity can occur as a consequence of changes at several locations – the gut itself, the spinal cord or the brain – or indeed at all three sites.

What increases the pain signal from the gut?

Experiments have been performed on animals, mainly rats, to try to answer this question. They show that inflammation increases the sensitivity of the sensory nerves in the gut. The chemical signals that carry out the inflammatory response, such as prostaglandins, histamine and serotonin, also interact with the sensory mechanisms, increasing their sensitivity.This means that, for any stimulus, such as an increased pressure within a part of the bowel, a stronger signal is generated. The signal remains higher for up to 6 weeks after the inflammation has ended and healing has taken place. People probably respond similarly to animals. It is common for an inflamed organ to be more sensitive, and to remain more sensitive for some time after healing. This is presumably an adaptive response to reduce the risk of re-injury. But it is unclear whether the increased sensitivity of the gut sensory mechanism persists for more than a few weeks in people, and to what extent it is responsible for the hypersensitivity of irritable bowel syndrome. It is interesting that tricyclic antidepressants such as amitriptyline can directly affect nerve cells in animals to reduce their sensitivity, as in humans amitriptyline is one of the most successful drugs used to control irritable bowel syndrome pain.

How is the pain signal modified in the spinal cord?

Nerves from our internal organs carrying pain signals initially go to the spinal cord. Here, the signal competes with other signals entering the cord before being transmitted upwards to the brain. Sensory signals will therefore compete with pain signals to reduce the transmission of the pain signal. This is the basis of the TENS (transcutaneous electrical nerve stimulation) machines in which electrical stimulation of the skin reduces back pain or labour pain, for example. The pain signal can also be increased or decreased by nerve pathways that originate in the brain and descend down the spinal cord.

So is the transmission and modification of pain signals in the spinal cord abnormal in people with irritable bowel syndrome?

A study from France has elegantly demonstrated this. How the spinal cord modifies signals can be seen by studying reflexes, which only need to travel through the spinal cord and are not affected by the brain. One such reflex, called the RIII reflex, involves stimulating a small nerve in the foot with an electric current. The signal from this nerve, travelling up the spinal cord, elicits a small reflex contraction in the biceps muscle of the upper arm. This contraction can be measured with electrodes placed over the muscle, and the strength of the contraction is proportional to the painful electric current stimulus applied to the nerve in the foot. The researchers measured the intensity of this reflex while at the same time inflating a balloon in the subject’s rectum. They found that distending the rectum in volunteers without irritable bowel syndrome inhibited this reflex by about 50%. This is to be expected as the pain signal from the rectum will compete with the pain signal from the foot. But when the experiment was repeated in 14 people with irritable bowel syndrome, the RIII reflex was not inhibited at all but actually increased by about 30%. This clearly shows an unconscious modification of pain signals in the spinal cord and of an effect in people with irritable bowel syndrome that would result in a stronger pain signal reaching the brain.

What happens in the brain?

Our understanding of how signals from the body are processed in the brain has progressed in recent years with the development of ‘functional’ brain scanning. These scans provide measures of activity in various parts of the brain in response to stimuli applied to other parts of the body. In positron emission tomography (PET) scanning, for example, slightly radioactive glucose is injected into the bloodstream. As the glucose is used up (metabolised), gamma radiation is emitted and detected by the scanner. The more radiation emitted by an area of brain, the greater the metabolic activity in that area, and metabolic activity is thought to represent nerves that are busy working. In functional magnetic resonance imaging (MRI), blood flow or oxygen use provides a measure of activity. We can combine knowledge gained from these scans with our existing knowledge of the function of different parts of the brain, which has come from anatomical studies and from studies of the results of injury. Nerve pathways from the body carrying pain signals ascend through the spinal cord to reach various centres in the brain that serve different functions. For example, spatial localisation (identifying which part of the body is sending a signal) is performed by the somatosensory cortex, while pain intensity is defined mainly in an area called the insula, and emotion is added by the anterior cingulate cortex. The signal from these areas is combined and, if strong enough, is consciously perceived.

Are there any differences between pain arising in the gastrointestinal organs and pain arising in the more external parts of the body such as the skin, muscle and bone?

There are two important differences. First, signals from the visceral (internal) organs such as the intestine are very poorly localised. A painful stimulation of a limb will show on a PET scan as an increase in activity in just the part of the somatosensory cortex that deals with that limb. By contrast, painful distension of part of the intestine will lead to a diffuse, more widespread, increase in activity within the somatosensory cortex on both sides of the brain. This is not that surprising as we already know that people can tell very accurately which part of the outside of their body is hurting but find it very difficult to localise pain from their internal organs. The second difference between gastrointestinal pain and pain from elsewhere in the body is that gastrointestinal pain evokes more intense activity in the anterior cingulate cortex. This is the part of the brain that mediates the emotional element of pain. It is well known that gastrointestinal pain evokes strong emotional responses. It is a more difficult pain to control and is frequently associated with depression. This may be part of the explanation for the difficulty in controlling irritable bowel syndrome pain, and the association of irritable bowel syndrome with psychological distress.

If irritable bowel syndrome is more common in women, does this mean there is a difference in how gastrointestinal sensations are processed in the female brain?

Brain imaging studies have been inconsistent, but it is beginning to look as though women have a greater activation of the anterior cingulate cortex than men in response to gastrointestinal pain. This is the part of the brain that mediates the emotional element of pain. The implication is that women have an enhanced emotional input to the pain signal.

And are there any differences in how the brain processes gastrointestinal sensations in people with irritable bowel syndrome?

Several studies have compared brain activity using PET and functional MRI scans in people with irritable bowel syndrome and people without irritable bowel syndrome (controls – an earlier answer explains why these are needed). Such studies can be difficult to interpret though. They can involve lying in a noisy claustrophobic MRI scanner waiting for a large balloon that has been inserted into the rectum to be painfully distended. Consequently, they are likely to be affected by the stress this causes in the volunteer. Even so, these studies have tended to show increased activity in the anterior cingulate cortex in people with irritable bowel syndrome, implying an increased emotional input to the pain signal. Interestingly, a recent study of women with irritable bowel syndrome has shown that treatment with low-dose amitriptyline reduced activity in the anterior cingulate cortex in response to rectal distension. Amitriptyline is an antidepressant frequently used in low doses to help the pain of irritable bowel syndrome.

Can you summarise how visceral hypersensitivity might explain irritable bowel syndrome?

The suggestion is that something happens in the intestine – an infection, infestation, inflammation of some sort, an allergic response or even just a change in the normal bacterial flora (the bacteria that live in the gut) following antibiotic use. The chemicals that bring about the inflammation and the hormones secreted as part of the inflammatory response then increase the sensitivity of the sensory mechanisms within the gut. Therefore, the usual functioning of the gut will generate a stronger signal.

Signals from the gut are more capable of initiating an emotional response than signals from other parts of the body. It is reasonable too to suppose that in people who are stressed, anxious or depressed for any reason, this emotional response will be greater. The emotional response integrates with the sensory signal, amplifying it. This amplification can occurs in the brain itself, as well as in the spinal cord, where the nerves are influenced by pathways descending from the brain.

Everyday events within the bowel can now generate sensory signals that, when overamplified, manifest as pain. It is reasonable to suppose that these overamplified signals themselves generate reflex responses that lead to disordered function, diarrhoea, constipation and bloating. The disordered function will generate still stronger sensory signals, which sets up a vicious circle. At times of stress, the symptoms are likely to be worse because the emotional input to the pain signal will be greater. It is also probable that the effects of any food intolerances or allergies will be magnified.

Visceral hypersensitivity, together with the fact that the brain processes signals from the gut in a different manner, is the leading hypothesis in irritable bowel syndrome. It covers many of the other theories and features of irritable bowel syndrome, and can provide the basis and rationale for further research and treatment.

What are the limitations of visceral hypersensitivity to explain irritable bowel syndrome?

There is evidence to back up several aspects of the visceral hypersensitivity story. We know that inflammation can sensitise sensory mechanisms, and we can demonstrate excess sensitivity to distension of the intestine. How closely this mimics irritable bowel syndrome is, however, unknown as pain is frequently thought to arise from strong contractions rather than excessive distension.

Furthermore, the concept of hypersensitivity has itself been questioned. When a volunteer in an experiment has a balloon inflated in her rectum, she knows that it might cause pain. If she has irritable bowel syndrome, she may have an even greater expectation of pain. The apparent hypersensitivity may thus be just a heightened expectation of pain. This bias can be avoided by doing a large inflation, a small inflation and a sham inflation (no inflation at all) in a random order so the volunteer cannot guess what is coming next. In such experiments, people with irritable bowel syndrome do not feel the balloon at lower volumes than normal, as would be expected from the hypersensitivity theory. Instead, they report any sensation as unpleasant or painful, suggesting that they get pain because they expect it.

It is also unclear just how sensory hypersensitivity results in disordered function. Indeed, there are people with irritable bowel syndrome in whom pain is a relatively minor feature compared with the disordered bowel habit or bloating. So why do the symptoms vary so much between different people, and why do they change with time? Finally, why does the hypersensitivity persist? Much remains mysterious.

What are the implications of the ‘visceral hypersensitivity’ theory for me?

The theory explains how people with symptoms can have completely normal medical tests. This is something that often worries people with irritable bowel syndrome. Moreover, it explains how a person’s emotional state can affect the severity of the symptoms. Finally, a better understanding of how the gut and the brain interact will allow us to develop new treatments. Some new drugs are already becoming available.

Could I have more than one cause for my irritable bowel syndrome?

It seems likely that irritable bowel syndrome is the culmination of many factors. For example, a simple infection may lead to visceral hypersensitivity, exacerbated by stress. Or a mild food intolerance may combine with small bowel bacterial overgrowth to produce profound diarrhoea. A multiplicity of factors combining to cause irritable bowel syndrome may explain why there is no simple solution and why the symptoms vary between people and over time.



■ There is a psychological element to irritable bowel syndrome in many people. It may not be the cause of the irritable bowel syndrome, but it can prolong and exacerbate the symptoms.
■ Small bowel bacterial overgrowth – an excess of bacteria in the normally sterile small bowel – may be part of the aetiology of irritable bowel syndrome. It should be particularly considered in those with diabetes, people who have had abdominal surgery and the elderly. It may cause diarrhoea-predominant irritable bowel syndrome. It is treated by antibiotics.
■ Food intolerance or allergy can produce the symptoms of irritable bowel syndrome, but whether it causes irritable bowel syndrome or is something separate is unknown. A dietary approach will work for some people, some of the time, to a certain extent.
■ Subtle inflammation in the bowel wall may be part of the aetiology of irritable bowel syndrome, but current anti-inflammatory medication does not work for irritable bowel syndrome.
■ Visceral hypersensitivity is the concept of enhanced perception, or enhanced responsiveness within the gut – even to everyday events.
■ Nerve signals from the gut are more capable of initiating an emotional response than are signals from other parts of the body.
■ The emotional response integrates with the sensory signal, amplifying it. This amplification can occur in the brain itself, as well as in the spinal cord, where the nerves are influenced by nerve pathways descending from the brain.
■ Our increasing understanding of how the gut and the brain are linked will lead to new treatments in the future.
■ irritable bowel syndrome may have more than one cause.