Irritable Bowel Syndrome

Etiology

The exact cause of IBS remains unknown; however, the following factors have been identified as contributing to its pathophysiology (see Image. Causes of IBS):

• Disordered gut-brain axis: Disorders of gut-brain interaction (DGBIs) primarily involve disruption of the gut-brain axis, which relies on complex signaling between the central (CNS) and enteric nervous systems (ENS) via neuronal, endocrine, immune, and metabolic pathways and is influenced by several factors, eg, genetics, diet, stress, and social factors.[3][4]

• Visceral hypersensitivity: Patients with IBS often exhibit heightened visceral sensitivity due to increased signaling from intestinal receptors to the central nervous system (CNS) in response to stimuli, eg, gas distension.[5][6]

• Gastrointestinal dysmotility: Patients with IBS may exhibit irregular contractions or transit delays, as seen in IBS with predominant constipation (IBS-C), or exaggerated motility, as seen in IBS with predominant diarrhea (IBS-D).

• Gut microbiota dysbiosis: Distinct alterations in microbiota have been linked to IBS subtypes.[7][8]

• Food intolerances: Food intolerances have been reported in 20% to 65% of patients with IBS; however, objective evidence to suggest causation is often lacking, and various other factors may contribute.[9]

• Low-grade mucosal inflammation: Lymphocyte infiltration and eosinophilia are commonly observed on histological examination, particularly in postinfectious and diarrhea-predominant cases.[10][11]

• Altered intestinal permeability: Increased intestinal permeability, particularly in IBS-D, has been linked to diet, microbiome shifts, and mediators such as serotonin and proteases.[12]

• Psychosocial factors: Psychological factors, eg, stress, can impact intestinal sensitivity, motility, and microbiota, thereby worsening IBS symptoms.[13]

Epidemiology

In the United States, the prevalence of IBS ranges from 7% to 16%.[14] An international meta-analysis estimated a pooled global prevalence of 11%, though significant variation exists depending on geographic region.[15] Socioeconomic status does not consistently correlate with the occurrence of IBS, although familial aggregation has been observed, indicating potential contributions from both genetic predisposition and sociocultural factors. IBS tends to be diagnosed more frequently in women within Western populations.[16] The condition occurs more commonly in younger adults, with a noticeable decline in prevalence after the age of 50.[17]

History and Physical

Conducting a thorough history remains essential for identifying patients who meet the Rome IV criteria for IBS. Detailed history-taking helps determine the specific IBS subtype, differentiate IBS from other conditions with overlapping symptoms, and assess for the presence of alarm features that may indicate underlying organic disease. Physical examination is typically normal in patients with IBS; however, some patients may experience tenderness upon palpation. 

According to the Rome IV criteria, a diagnosis of IBS requires recurrent abdominal pain occurring, on average, at least 1 day per week over the past 3 months. This pain must be associated with at least 2 of the following: defecation, a change in stool frequency, or a change in stool form (appearance). These criteria must have been fulfilled within the last 3 months, with symptom onset occurring at least 6 months before diagnosis. This structured approach supports timely and accurate diagnosis, allowing for appropriate management and minimizing unnecessary investigations.[18]

Diagnostic Criteria for IBS Subtypes

The following IBS subtypes are classified by predominant bowel habits based on stool form on days with at least 1 abnormal bowel movement:

• IBS with predominant constipation (IBS-C): >25% of bowel movements with Bristol Stool Form Scale (BSFS) types 1 or 2 and <25% with BSFS types 6 or 7
• IBS with predominant diarrhea (IBS-D): >25% of bowel movements with BSFS types 6 or 7 and <25% with BSFS types 1 or 2
• IBS with mixed bowel habits (IBS-M): >25% of bowel movements with BSFS types 1 or 2 and >25% with BSFS types 6 or 7
• IBS Unclassified (IBS-U): an unclassified subcategory that meets the criteria for IBS, but bowel movements cannot accurately be categorized into 1 of the 3 subgroups

Differentiating IBS from other gastrointestinal conditions that mimic IBS symptoms, eg, inflammatory bowel disease (IBD) and celiac disease, is essential in patients with diarrhea-predominant IBS. Similarly, in patients with constipation-predominant IBS, a history of straining during stool passage and the need for manual disimpaction could suggest a rectal evacuation disorder.

Red Flag Clinical Features

The presence of red flags or alarm symptoms in the patient's history should raise suspicion of an underlying organic disorder that warrants further diagnostic evaluation, including:

• New symptom onset at the age of 50 or older
• Blood in the stools (red blood or black, tarry stool)
• Fever, shaking chills, or night sweats
• Nighttime symptoms that wake you up
• Unintentional weight loss
• Change in your typical IBS symptoms (eg, new and different pain)
• Recent use of antibiotics
• Family history of other GI diseases, eg, cancer, inflammatory bowel disease, or celiac disease

Evaluation

Current guidelines recommend a limited diagnostic evaluation to rule out other disorders that present with symptoms similar to those of IBS. This approach helps avoid unnecessary testing and supports the timely initiation of appropriate therapy.[19]

For patients with diarrhea-predominant IBS (IBS-D), recommended testing includes celiac serologies, fecal calprotectin or lactoferrin, and C-reactive protein (CRP) to exclude inflammatory bowel disease. Additional testing for bile acid diarrhea may be appropriate when clinically suspected. In regions where Giardia is endemic, a Giardia stool antigen test is also advised. Routine testing for food allergies or sensitivities, general stool analyses, or hydrogen breath testing for small intestinal bacterial overgrowth (SIBO) should be reserved for cases where clinical suspicion specifically supports those diagnoses.

In patients with constipation-predominant IBS (IBS-C), recommended evaluations include celiac serologies and anorectal physiology testing to assess for pelvic floor dysfunction. In the absence of alarm symptoms, routine colonoscopy is not advised for patients younger than 45 years.

Adopting a positive diagnostic strategy—focused on confirming IBS rather than excluding other conditions—enhances cost-effectiveness and enables prompt initiation of targeted treatment.[19] This method reinforces the importance of clinical criteria in guiding both diagnosis and management.

Treatment / Management

The treatment involves a multifactorial approach that integrates dietary changes, lifestyle modifications, pharmacologic therapy, and psychological interventions. Each component targets different aspects of the disorder’s pathophysiology and symptomatology, with individualized treatment plans tailored to the IBS subtype and patient preferences.

Patient-Clinician Alliance

A strong therapeutic alliance and shared decision-making 

A strong patient-clinician relationship and shared decision-making form the foundation of effective care for individuals with IBS. This therapeutic alliance enhances motivation, interpersonal support, and the patient’s expectation of symptom improvement.[20] Trust, mutual goal setting, patient education, reassurance, and the consideration of psychological factors all contribute to a successful partnership. Establishing this connection enables patients to actively engage in their care and adhere to treatment recommendations more consistently.(B2)

Lifestyle Modifications

Lifestyle modifications can improve overall IBS symptom control. Regular physical activity and improved sleep hygiene have been shown to have benefits in some studies, particularly in reducing global symptoms, eg, abdominal pain, cramping, and bloating. These simple, non-pharmacologic strategies often serve as first-line interventions and support long-term well-being.[21][22](A1)

Dietary Modifications

Dietary interventions play a central role in IBS management, as many patients report symptom exacerbation following certain foods. Referral to a registered dietitian nutritionist remains essential for patients willing to modify their diet. The American Gastroenterological Association (AGA) identifies the low-FODMAP (fermentable oligo-, di-, and monosaccharides and polyols) diet as the most evidence-based dietary intervention for IBS. This approach consists of the following 3 phases:

• A 4- to 6-week restriction period, systematic
• Reintroduction of FODMAP foods
• Individualized personalization based on symptom response [23]

The AGA and American College of Gastroenterology (ACG) also strongly support the use of soluble fiber for improving global IBS symptoms.[19][23][24] While other diets, eg, the gluten-free diet (GFD), have shown promise in observational studies, randomized controlled trials have not confirmed their efficacy. Long-term restrictive diets that lack clinical benefit should be discontinued due to the potential for nutritional deficiencies.[23] If dietary and lifestyle modifications fail to control symptoms adequately, pharmacologic therapy should be initiated based on IBS subtype and symptom severity (eg, abdominal pain).(A1)

Constipation-Predominant IBS

In constipation-predominant IBS (IBS-C), the AGA recommends osmotic laxatives like polyethylene glycol (PEG) as first-line treatment.[25] Although PEG effectively relieves constipation, it offers limited benefit for bloating or abdominal pain. Second-line agents include secretagogues such as linaclotide, lubiprostone, and tenapanor, which enhance intestinal secretion and motility. Tegaserod, a 5-HT4 receptor agonist, serves as a third-line option approved for use in women younger than 65 who have no history of cardiovascular ischemic events.

Diarrhea-Predominant IBS

For diarrhea-predominant IBS (IBS-D), first-line therapies include loperamide, a synthetic mu-opioid receptor agonist, and bile acid sequestrants, which may benefit patients with bile acid malabsorption, a condition present in up to 50% of those with IBS-D.[26] Several second-line treatment options are available. Rifaximin, a nonabsorbable antibiotic, is recommended by both AGA and ACG for moderate to severe IBS-D and may be used for retreatment in cases of symptom relapse.[27] (A1)

Additional gut-specific pharmacotherapy options include eluxadoline, a mixed mu- and kappa-opioid receptor agonist, which is contraindicated in patients with gallbladder disease or high alcohol intake (>3 alcoholic beverages/day). Alosetron, a 5-HT3 receptor antagonist, may be used as a third-line agent in women with severe IBS-D but carries a black box warning for the risk of ischemic colitis.

Treatment of Global IBS Symptoms

For global IBS symptoms such as abdominal pain, cramping, and bloating, antispasmodics—including peppermint oil and anticholinergic medications like hyoscine or dicyclomine—are frequently used in clinical practice.[28][29] These agents reduce smooth muscle contraction and may diminish visceral hypersensitivity.[30] Tricyclic antidepressants (TCAs), eg, amitriptyline, nortriptyline, imipramine, and desipramine, act as neuromodulators that target norepinephrine and dopamine receptors.[31] Their anticholinergic properties and ability to slow gastric transit also contribute to symptom relief, particularly in patients with IBS-D.(A1)

Gut-Directed Psychotherapy

Gut-directed psychotherapy offers another valuable treatment option, particularly for patients with IBS linked to psychological stress or mood disorders. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy have demonstrated effectiveness in reducing the frequency and severity of symptoms, primarily in patients with mood-directed IBS symptoms. These interventions address the disrupted gut-brain axis believed to underlie IBS. Current guidelines do not recommend selective serotonin reuptake inhibitors (SSRIs) or fecal microbiota transplants for IBS management, given insufficient evidence supporting their use in this context.[32][33][34](A1)

Differential Diagnosis

The differential diagnosis of IBS is broad. A limited diagnostic evaluation is recommended if the patient meets the criteria for diagnosis of IBS. Depending on the predominant symptoms, several differential diagnoses should be considered, including:

• IBS-D 
  • Celiac disease
  • Inflammatory bowel disease (IBD)
  • Microscopic colitis
  • Bile acid diarrhea
  • Small intestinal bacterial overgrowth (SIBO)
  • Chronic infections (eg, giardiasis)
  • Food intolerance (lactose, fructose)
  • Medications
  • Malignancy
• IBS-C 
  • Slow colonic transit
  • Dyssynergic defecation
  • Endocrine abnormalities (hypothyroidism, hypercalcemia)
  • Medications
  • Malignancy

Prognosis

IBS is a chronic condition characterized by recurrent symptoms of varying severity. However, life expectancy in individuals with IBS is comparable to that of the general population. The diagnosis typically remains stable during follow-up. The use of ambulatory health services by IBS patients can be reduced when a positive relationship and strong rapport are established between the patient and clinician.[35]

Complications

IBS generally remains a manageable condition, with complications occurring infrequently. However, certain patients may experience adverse effects related to the condition and its management.

Physical complications, eg, hemorrhoids, anal fissures, and fecal impaction may develop, particularly in those with constipation-predominant IBS. Additionally, patients who follow overly restrictive diets in an attempt to control their symptoms face an increased risk of nutritional deficiencies due to inadequate intake of essential nutrients.

Chronic symptoms and lifestyle disruptions associated with IBS often contribute to the development or worsening of mental health issues, including depression, anxiety, and mood disorders. These psychological effects may stem from the persistent discomfort and unpredictability of symptoms. Additionally, IBS can also significantly impair quality of life. Frequent abdominal pain, altered bowel habits, and bloating may interfere with work performance, academic responsibilities, social engagements, and personal relationships. Many patients report sleep disturbances as well, further compounding physical and emotional stress.