Irritable bowel syndrome

Irritable bowel syndrome is a chronic, functional bowel disorder characterised by abdominal pain and altered bowel habits.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGID). It is characterised by chronic abdominal pain and altered bowel habits (e.g. diarrhoea and/or constipation).

The term ‘functional’ refers to a condition that is not associated with structural or biochemical abnormalities that are detectable with current routine diagnostic tests. Although the exact cause of FGIDs is unknown, it is thought to be due to dysregulation in communication between the gut and brain at multiple levels. This has led to the term 'disorders of the gut-brain interaction'.

IBS is very common and accounts for a significant number of referrals to gastroenterologists. It is estimated to affect 5-20% of the general population and can have a significant impact on quality of life (QOL).

These are disorders of the gut-brain interaction that do not have a detectable structural or biochemical abnormality.

Functional GI disorders (FGID) are extremely common and can affect most parts of the gastrointestinal tract. They are not associated with structural or biochemical abnormalities that are detectable with current routine diagnostic tests. They are thought to be the result of dysregulation between gut and brain. IBS is one of the most well recognised of these disorders.

Classification of functional disorders

Unfortunately, there is no single test for functional disorders and diagnosis relies on diagnostic criteria. Development of these criteria began in the 1980s based on expert opinion amongst different committees. The aim was to answer difficult questions about GI disorders with little scientific evidence.

In 1994, the book “The Functional Gastrointestinal Disorders: Diagnosis, Pathophysiology, and Treatment” was published, which is considered the Rome I criteria. Over the next three decades, several versions have been released, each using an increasing quantity of evidence to make decisions on diagnosis and management.

Rome IV criteria

Rome IV is the latest edition, which was published in 2016. This focuses more on the gut-brain interaction and gives recommendations on both diagnosis and treatment for all FGID that are divided by organ.

• Oesophagus (e.g. Functional heartburn, functional dysphagia)
• Gastroduodenal (e.g. Functional dyspepsia, belching disorders)
• Bowel (e.g. IBS, functional constipation, functional diarrhoea)
• Hepatobiliary (e.g. Functional biliary sphincter of Oddi disorder)
• Anorectal (e.g. Functional defecation disorders)

IBS is a common condition that is probably underestimated as many people do not seek medical attention.

The prevalence of IBS is variable depending on the study, diagnostic criteria and geographical location.

In the UK, the estimated prevalence in one population-based study was 5.5%, with a prevalence of 5-10% across most European countries. A study by Lovell et al showed prevalence is higher among females with an odds ratio of 1.67 (95% CI 1.53–1.82). It is more common in younger patients.

Risk factors

Numerous risk factors have been linked to the development of IBS, but some have much greater evidence behind them. Below we list some of the most well recognised, but this is not an exhaustive list.

• Female sex
• Younger age
• Stressful life events
• Anxiety and/or depression
• Gastrointestinal infection (post-infectious IBS)
• Somatic symptoms (e.g. joint pain, migraine)
• Endometriosis
• Family history of mental illness

Associated conditions

IBS is linked with numerous other functional gastrointestinal disorders (e.g. functional dyspepsia), functional non-gastrointestinal disorders and psychiatric conditions (e.g. depression, anxiety). Commonly associated functional non-gastrointestinal disorders include:

• Chronic pelvic pain syndrome
• Overactive bladder
• Premenstural syndrome
• Sexual dysfunction
• Fibromyalgia
• Chronic fatigue syndrome

The exact cause of IBS is unknown, but it is considered a disorder of gut-brain interaction.

Traditionally, IBS was considered a problem between altered gastric motility, visceral hypersensitivity, and psychosocial factors. Visceral hypersensitivity describes a heightened response to a perceived stimuli via internal organ pain receptors known as nociceptors.

There is now more emphasis on the interaction between the brain and gut. This includes the population of microorganisms that normally reside within the GI tract termed the microbiome. This has lead to the term ‘disorders of the gut-brain interaction’, which is quoted in Rome IV. Despite progress, there are still inconsistencies in IBS research and lack of a unifying concept.

IBS is heterogeneous disoder characterised by a multiple disrupted mechanisms:

• Motility problems
• Visceral hypersensitivity
• Altered mucosal and immune function
• Gut microbiome alteration
• Food sensitivity
• Psychosocial factors

Gastrointestinal motility

Motility refers to how fast digested food is transported through the intestines. Various motility disorders have been observed in IBS including increased frequency of contractions, irregularity of contractions and prolonged transit through the bowel. The brain, via the autonomic nervous system, can significantly impact intestinal motility.

Visceral hypersensitivity

This describes a heightened response to a perceived stimuli via nociceptors within the bowel. These receptors transmit signals to the brain for processing, but it is unclear whether the hypersensitivity is predominantly mediated by the enteric nervous system (i.e. local GI nerves), through central brain processing, or a combination of both.

Patients with IBS are more sensitive to distention of the bowel and there is evidence for higher activation of visceral and somatic pain pathways. It is postulated these affects are mediated by mast cells and enteroendocrine cells through release of histamine and serotonin, respectively.

Altered mucosal and immune function

The epithelial lining of the GI tract is a large surface area that is constantly in contact with the environment and billions of bacteria that make up the gut microbiome. This causes a constant challenge to the intestinal immune system. Altered mucosal and immune function has been identified in some patients of IBS, particularly those with diarrhoea predominant symptoms. Two key factors are intestinal permeability and immune activation.

• Increased intestinal permeablity: been identified in patients with IBS. Causes low-grade immune cell infiltration, diarrhoea, and increased pain severity.
• Immune system activation: increased activation of immune cells (e.g. mast cells), increased lymphocyte infiltration and elevated inflammatory cytokines in a subset of IBS patients. Up to 10% of patients develop IBS following an episode of gastroenteritis.

Gut microbiome alteration

The gut microbiome refers to the diverse population of microorganisms that inhabit the GI tract and have a systemic influence of health. The microbiome is complex and has a large diversity between individuals. There is growing evidence surrounding the relative contributions of different populations of bacteria to development of IBS. Among IBS patients, some bacterial populations are increased and others decreased.

Food sensitivity

This is a complex area and many patients report a worsening of IBS symptoms with different foods (e.g. carbohydrate, gluten). These are generally related to food intolerances that describe a physiological reaction to food allergens that is not associated with an immune response (e.g. classic IgE-mediated allergy).

One area with growing interest is carbohydrate malabsorption. It is suggested that fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) enter the distal small bowl and colon where they are fermented and converted into small chain fatty acids (SCFAs). This leads to increased symptoms, intestinal permeability and possibly inflammation. This theory has lead to the recommendation of low FODMAP diets in both IBS and inflammatory bowel disease (IBD) patients.

Psychosocial factors

It is well recognised that patients with IBS have more lifetime and daily stressful events, increased mental heath illness including anxiety, depression and phobias, and an association with previous abuse. The link between these factors and IBS has been hypothesised to relate to corticotropin releasing factor.

IBS is characterised by chronic abdominal pain and altered bowel habits.

Abdominal pain

• Site: commonly lower abdomen, but variable and may be diffuse
• Origin: chronic pain, at least 1 day per week, but often more frequent
• Character: typically cramping, acute episodes of sharp pain may occur
• Associated factors: pain is frequently related to defecation. May improve or worsen
• Exacerbating factors: food and stress may worsen symptoms

Altered bowel habits

• Diarrhoea: frequent, loose stools. Up to 50% report mucous discharge. Generally occurs in waking hours. Tenesmus may be present (sensation of incomplete bowel emptying)
• Constipation: infrequent, hard stools. Often described as pellets

Other GI features

• Bloating/Distention
• Belching
• Nausea
• Others: IBS may overlap with other functional GI disorders

Red flags

These refer to features that warrant investigation for an alternative cause (e.g. colorectal cancer, IBD). Despite their presence, most patients will ultimately have negative tests.

• Onset of symptoms > 50 years
• Rectal bleeding or melaena
• Unexplained weight loss (> 10% in 3 months)
• Palpable abdominal mass
• Nocturnal diarrhoea
• Significant family history (e.g. colorectal cancer, inflammatory bowel disease or coeliac disease)
• Anaemia or raised inflammatory markers

The Bristol stool chart is a way of describing the shape and type of faeces.

Stool chart

• Type 1 - Separate hard lumps, like pellets
• Type 2 - Sausage-shaped but lumpy
• Type 3 - Like a sausage but cracks on surface
• Type 4 - Like a sausage, smooth and soft
• Type 5 - Soft blobs, clear-cut edges
• Type 6 - Mushy stool. Fluffy pieces with ragged edges
• Type 7 - Watery, no solid pieces

The diagnosis of IBS is based on the Rome IV criteria.

IBS should be a positive clinical diagnosis based on symptoms fulfilling the Rome IV criteria. This should be in conjunction with normal results on a limited numbers of investigations needed to rule out alternative diagnoses with reasonable certainty.

Rome IV criteria

IBS is defined as recurrent abdominal pain that has occurred, on average, at least one day per week over the last three months and symptoms begin at least six months ago. In addition, pain is associated with ≥2 of the following criteria:

• Related to defecation
• Associated with change in stool frequency
• Associated with change in stool form (appearance)

Once the diagnosis is made, patients should be classified into a subtype (see classification).

Differential diagnosis

Several other gastrointestinal disorders may present similarly to IBS. These require exclusion, particularly when red flag or alarm features are present within the clinical assessment.

• IBD
• Colorectal cancer
• Microscopic colitis
• Diverticular disease
• Small intestinal bacterial overgrowth
• Coeliac disease
• Chronic pancreatitis
• Neurological disorders (e.g. Parkinson’s)
• Medications

IBS is classified into different subtypes.

After meeting the diagnostic criteria, IBS can be differentiated into a subtype based on the predominant abnormal bowel habit.

• IBS with predominant constipation (IBS-C): > 25% of bowel motions are usually constipation (Bristol stool type 1/2)
• IBS with predominant diarrhoea (IBS-D): > 25% of bowel motions are usually diarrhoea (Bristol stool type 6/7)
• IBS with mixed bowel habits (IBS-M): > 25% of bowel motions are constipation (Bristol stool type 1/2) and > 25% of bowel motions are diarrhoea (Bristol stool type 6/7)
• IBS unclassified (IBS-U): cannot accurately classify into one of the three subtypes

This is a sensitive biomarkers of intestinal inflammation.

Faecal calprotectin (FCP) is a sensitive and specific biomarker for intestinal inflammation. It can be used to aid differentiation between IBS and IBD.

Due to its high negative predictive value (i.e. a negative test means it is highly likely you don’t have the disease), it can be used as a screening tool in primary care among young patients with chronic diarrhoea to differentiate between IBS and IBD. Assays are variable but generally a value < 100 mcg/g is considered negative and local guidelines should be followed.

• FCP < 100 mcg/g: negative
• FCP 100-250 mcg/g: grey area (consider gastroenterology opinion)
• FCP > 250 mcg/g: positive (warrants endoscopic assessment)

Only a limited number of investigations needed to rule out alternative diagnoses with reasonable certainty should be completed.

Investigations may be used to exclude alternative diagnoses as part of the initial work-up depending on the likelihood of a suspected organic disease. Basic investigations in the absence of reg flags include:

• Full blood count
• C-reactive protein
• Faecal calprotectin
• Coeliac testing

The next level of investigations include imaging and endoscopy.

A variety of treatment options may be offered to patients depending on these severity of IBS.

When managing IBS, it is important to obtain a good patient relationship, make a positive diagnosis, explain the chronic nature of the condition and establish realistic expectations. There are no treatments that cure IBS, but many are available to alleviate symptoms and improve QOL.

There are three key aspects to management:

• Nutrition
• Drug therapy
• Psychological therapies

Several dietary modifications can be discussed with patients with IBS.

A variety of dietary modifications can be trialed to help alleviate symptoms. These depend on the impact that food has on patients symptoms. Information should be coordinated by a trained dietitian to avoid overly restrictive dietary changes that may impact on nutrition (e.g. malnutrition, vitamin deficiencies).

Dietary modifications can include:

• Exclusion of gas-producing foods: these are food that increase flatulence and bloating (e.g. beans, onion, carrots, bananas, caffeine, alcohol, wheat germ)
• Lactose avoidance: some patients with IBS may have co-existent lactose intolerance leading to worsening of symptoms
• Low FODMAP diet: these dietary modifications have been confirmed in randomised trials. This includes reducing various quantities of oligosaccharides (e.g. wheat, rye, various fruits), disaccharides (e.g. milk, yoghurt), monosaccharides (e.g. fructose containing food), and polyols (e.g. low calorie sweeteners). Advice of a dietitian should be followed
• Gluten avoidance: Non-coeliac gluten sensitivity has been suggested to influence symptoms. Although this may be related to the fructan (carbohydrate) contained within gluten products

Medications are generally reserved for patients with moderate to severe IBS symptoms that impair QOL.

The choice of medication to treat IBS depends on the predominant symptom (e.g. constipation, diarrhoea and/or pain)

Constipation

The use of laxatives are the principle treatment in IBS-C.

• First line: bulk-forming laxative (e.g. ispaghula husk)
• Second line: osmotic laxatives (e.g. movicol). Lactulose is not recommended in IBS-C.
• Third line: consider newer laxative classes such as Chloride channel activators (e.g. Lubiprostone), Guanylate cyclase agonists (e.g. Linaclotide) or 5-hydroxytryptamine 4 receptor agonists (e.g. Prucalopride).

Third-line agents may be considered for patients with IBS-C or chronic constipation that have not responded to maximal tolerated doses of conventional laxatives. There are different prescribing indications for these drugs and important safety considerations (e.g. ischaemic colitis and prucalopride).

Diarrhoea

The use of anti-diarrhoeal agents are the principle treatment in IBC-D.

• First line: loperamide is the principle anti-diarrhoeal agent, which is an opioid receptor agonist that slows bowel transit. The initial dose is 2 mg 45 minutes before a meal. Its use should be limited in IBD-M.
• Second line: bile acid sequestrants (e.g. cholestyramine, colesevelam) may be used due to the high prevalence of bile acid malabsorption. Where possible, the diagnosis of bile acid malabsorption should be confirmed with SeHCAT testing before embarking on therapy.
• Other options: serotonin antagonists (e.g. ondansetron) may be prescribed. Ondansetron is a commonly prescribed anti-emetic of which constipation is a common side-effect.

Abdominal pain

Anti-spasmodics and anti-depressants can be used to treat abdominal pain in IBS.

• Anti-spasmodics: Buscopan (Hyoscine butylbromide) and mebeverine are commonly prescribed on an 'as-needed' basis. These provide short-term relief of pain by relaxing smooth muscle. Buscopan is an antimuscarinic whereas mebeverine works directly on gastrointestinal smooth muscle.
• Anti-depressants: low dose tricyclic antidepressants are commonly prescribed as neuromodulators in many functional gastrointestinal disorders like IBS. They have analgesic properties independent of their effect on mood and have additional benefit in IBD-D by slowing transit time. Selective serotonin reuptake inhibitors may be used if depression is a cofactor.
• Other options: a trial of antibiotics may be offered to patients with IBS without constipation who have ongoing pain/bloating despite dietary modifications, anti-spasmodics and antidepressants. Rifaximin is often used.

Psychological therapies may be used as the primary treatment or as an adjunct in IBS.

There are several psychological therapies with an evidence-base that can be used in IBS.

• Cognitive–behavioural therapy (CBT): this has the best evidence in the treatment of IBS. CBT is based on the assumption that IBS symptoms are a response to stressful life events and maladaptive behaviour. CBT attempts to modify this.
• Psychodynamic (interpersonal) therapy: this looks at symptoms as a consequence of difficult relationships or conflicts.
• Gut-directed hypnosis: this type of therapy addresses the miscommunication between gut and brain.
• Mindfulness-based therapy: this is a type of meditation that focuses on strategies for coping with IBS symptoms.

IBS is a chronic gastrointestinal disorder in which symptoms may fluctuate over many years.

There is limited information on the long-term outcome in patients with IBS. Only a small proportion of patients are diagnosed with an alternative GI disorder on follow-up following initial negative tests.

It is important to recognise IBS as a chronic GI disorder with fluctuation in symptoms over years. The fluctuation in symptoms was addressed in one systemic review over a median follow-up of two years. They looked at the proportion of patients with worsening, unchanged or improved symptoms:

• Worsening symptoms (2-18%)
• Unchanged symptoms (30-50%)
• Improved symptoms (12-38%)

In patients with post-infectious IBS that represents a unique cohort of patients, symptoms resolve in up to 50% within 6-8 years.

Last updated: July 2021