IBS affects persons regardless of age and biological sex but is most common in women and younger individuals. The worldwide prevalence of IBS among adults is between 4.1% (Rome IV criteria) and 10.1% (Rome III criteria) [213]. A population-based survey among 5,931 adults found that prevalence values (4.4% to 4.8%) of IBS (Rome IV criteria) are similar in the United States, Canada, and United Kingdom [214]. The estimated lifetime prevalence of IBS in adult North American and European populations is 10% to 20%, but only 5% to 7% have been diagnosed. IBS shows highest prevalence in South America (21%) and lowest prevalence in Southeast Asia (7%) [5,6].

IBS is among the most common diagnosed GI disorders, accounting for 41% of patients with functional GI symptoms [5,6,7]. Among clinical populations, IBS accounts for 12% of all patients seen in primary care and 28% in gastroenterology clinics [7]. In the United States, patients with IBS are evenly distributed among three common presenting clinical patterns: IBS with diarrhea (IBS-D), IBS with constipation (IBS-C), and mixed IBS (IBS-M); in Europe, most patients reportedly have either IBS-C or IBS-M [5,6].

Of all persons with IBS symptoms, only a minority seek primary care medical attention, estimated at 10% to 70% in European countries and around 30% in the United States. In a 2017 online survey of 1,924 participants with a history of gastrointestinal symptoms, 43% of individuals who met the criteria for IBS-D had not received a formal diagnosis of the disorder [9]. Patients with IBS-D tend to seek medical attention at higher rates than those with IBS-C or IBS-M. Those seeking medical care report greater levels of pain and anxiety and greater impact on quality of life. In contrast, GI symptom severity does not differ greatly between the two groups [4,8,10].

Patients with panic disorder may suffer from IBS as well; the prevalence of IBS symptom characteristics in patients with panic disorder is 25% to 44% [12]. A strong association is also found between IBS and generalized anxiety disorder, and patients with comorbid IBS and generalized anxiety disorder have greater functional impairment and depressive symptoms. Post-traumatic stress disorder (PTSD) is also prevalent, and as many as 36% of patients with IBS meet the criteria for lifetime diagnosis for PTSD. Major depressive disorder is the most frequent psychiatric comorbidity in IBS. Patients with major depressive disorder showed a 27% to 47% prevalence of IBS, although patients with major depressive disorder in remission did not differ from healthy controls in terms of IBS symptoms [12].

For most patients with IBS, the symptoms of IBS are intermittent and over time show considerable fluctuation in frequency and duration. In the first three months after diagnosis, patients experience an average of four distinct symptom episodes per month, with the longest episode averaging five days, and most patients experience symptoms more than 50% of the days. One year after initial diagnosis, 30% to 45% of patients report they now have prolonged symptom-free periods. In the second year of follow-up, some patients experience symptom resolution, while others develop new symptoms and rate of symptomatic IBS episodes remains stable. After 10 years, 50% to 70% of patients report persistent symptoms [33,34,35].

Bloating is perhaps the most bothersome IBS symptom to patients. Bloating often leads to seeking medical care and adversely affects energy level, food intake, and physical functioning [51]. A large population-based study in Japan found abdominal bloating to be the most bothersome symptom in patients with IBS-C. The levels of anxiety and distress in daily life were associated with severity of abdominal pain, discomfort, and bloating, and abdominal bloating was more likely to occur after a meal, at work/school, and during times of stress [52].

Functional GI disorders are idiopathic disorders of gut-brain interaction and, unlike organic disease and motility disorders, diagnosis involves identification of symptom clusters. These disorders may be further categorized as functional bowel, functional esophageal, IBS, noncardiac chest pain, functional gastroduodenal, and other disorders.

Early life trauma is associated with increased risk for IBS and other functional GI disorders, major psychiatric disorders, ischemic heart disease, diabetes, asthma, and other medical disorders in adulthood [60]. In general, patients with IBS report a high prevalence of adverse life events, including childhood physical punishment, emotional abuse, and sexual abuse. This psychosocial history is related to greater functional GI disorder severity and higher rates of psychological distress and impaired daily functioning. These effects increase health care seeking and explain the higher prevalence of abuse histories among patients with IBS seen in specialty clinics than in primary care; those with mild IBS symptoms and psychosocial histories may not seek medical care. A past history of childhood abuse is also common (approaching 50%) in patients with chronic functional somatic syndromes such as chronic pelvic pain, headaches, and fibromyalgia [61,62,63].

Functional GI disorder onset frequently coincides with experiencing a highly threatening event, such as the breakup of an intimate relationship. Stressful life events are associated with symptom exacerbation and frequent health care-seeking in adults with IBS. Chronic life stress is the greatest predictor of IBS symptom severity one to two years after diagnosis and negatively affects functional GI disorder treatment outcomes. Presence of a single stressor within 6 months of initiating IBS treatment predicts poor outcomes and higher symptom intensity at 16-month follow-up [55,64].

The prevalence of IBS is increased six- to seven-fold in persons who have experienced a prior infectious gastroenteritis or enterocolitis, and postinfectious IBS accounts for 5% to 25% of all cases of IBS [80]. IBS develops in 3% to 30% of patients following acute gastroenteritis, illustrating an acute pathogen and host interaction that predisposes to development of chronic IBS [5,81]. Factors with the greatest risk for postinfectious IBS are elongating toxin and longer duration of the initial illness [82,83]. Other predisposing factors include:

Gut dysbiosis is defined as an imbalanced or maladapted, but stable, gut ecosystem that has potential for reducing homeostasis and increasing the risk of disease pathogenesis [88]. Gut dysbiosis may influence the natural history of psychiatric disorders, cognitive disorders, and chronic visceral pain (due to brain-gut mediation). The intestinal flora of patients with IBS differs from healthy persons, and intestinal flora profiles also differ among IBS subtypes [89]. Deficiency in Bifidobacterium has been associated with greater abdominal pain and bloating. As such, treatment with probiotics has shown some promise in alleviating symptoms in IBS. In one study, probiotic administration was found to alter central processing of emotional stimuli and resting brain connectivity in sensory and affective brain circuits. The hypothesis of a microbiome gut-brain axis is emerging, and there is a possibility that gut microbiota will represent a therapeutic target in the treatment of IBS [55,90,91].

Many patients report that certain foods trigger IBS symptoms. The contribution of true food allergies is small, but food intolerances are common in patients with IBS. Gluten (present in wheat products) is increasingly recognized as an important symptom trigger in patients with IBS and inducer of IBS-like symptoms in persons without IBS diagnosis. Non-celiac gluten sensitivity is an emerging syndrome provoked by gluten ingestion in patients in whom celiac disease and wheat allergy are ruled out. Other triggers of non-celiac gluten sensitivity pathogenesis include wheat proteins (i.e., amylase and trypsin inhibitors) and FODMAPs (fermentable oligo-, di-, monosaccharides, and polyols) [94,95]. Emerging evidence supports gluten-free and low-FODMAPs diets for patients with IBS. FODMAPs are poorly absorbed carbohydrates that can induce osmotic effects, result in increased fermentation in the small bowel or colon, and trigger symptom exacerbation in patients with IBS with abnormal gut function or sensitivity [5,94].

Visceral hypersensitivity (also referred to as sensitization) describes lowered thresholds for visceral pain and occurs in the majority of patients with IBS. In these patients, lower pain thresholds are reflected by an exaggerated pain response to normally modest GI discomfort and/or painful response to stimuli that are not normally pain- or discomfort-inducing (e.g., normal bowel function). Visceral sensitivity is amplified in patients with IBS [15].

Female patients with IBS have shown increased cortical thickness in the somatosensory cortex and decreased cortical thickness in pain processing regions, including the insula and anterior cingulate cortex. IBS symptom severity is negatively correlated with cingulate thickness, suggesting a role for loss of neural density in symptom generation [106,110,111].

Patients with IBS have also shown decreased gray matter volumes in widespread regions, with early life trauma contributing to these decreases [106]. Decreased gray matter density in prefrontal and posterior parietal cortex areas is consistent with the close relationship between IBS and mood disorders. Pain catastrophizing negatively correlates with the degree of cortical thickness in the prefrontal cortex [112,113,114].

Descriptions of pain associated with IBS often change, but the pain is typically described as cramping discomfort that is diffuse or variable in location, without radiation. The most common site of pain is the lower abdomen, specifically the left lower quadrant. Many patients experience periodic exacerbations that vary in intensity from mild to severe; others describe acute episodes of sharp pain, often superimposed on a more constant dull ache. Meals may precipitate or aggravate the pain. Some patients report that pain is worsened by defecation, others that the pain is relieved by defecation. On occasion, the combination of enhanced colonic peristalsis and trapped gas in the splenic flexure may produce severe left upper quadrant abdominal pain or referred pain to the chest that mimics that of cardiac ischemia. Termed splenic flexure syndrome, balloon inflation in the splenic flexure will provoke this pain and should be considered in selected patients in order to differentiate it from more serious causes of chest or left upper quadrant abdominal pain [118].

In 2016, the Rome IV guidelines were published to address these criticisms and improve guidance to healthcare providers based on latest scientific and clinical evidence. Important changes in Rome IV IBS diagnostic criteria include [2,3]:

The Bristol Stool Form Scale (BSFS) illustrates and describes the appearance of seven different stool types that correspond to intestinal transit time ranging from severe constipation (Types 1 and 2) to diarrhea (Type 7). Patients can use the BSFS to record frequency and subtype of their stools [124]:

The diagnosis of IBS relies on a thorough patient history, physical examination, and limited laboratory testing. While not necessary for diagnosis, a brief psychosocial assessment should be performed in all patients. In most patients who fulfill Rome IV diagnostic criteria and for whom alarm features are absent, the need for diagnostic testing should be minimal; performing a battery of tests in all patients suspected of IBS is not warranted. However, focused diagnostic testing may be required to differentiate IBS from several conditions with mimicking symptoms when ambiguity is present. IBS mimics include inflammatory bowel disease, celiac disease, lactose and fructose intolerance, and microscopic colitis [3].

Ask patients for specific information regarding bowel habits and stool characteristics, as this informs subtyping of their IBS. A diagnosis of unclassified IBS (IBS-U) is reserved for patients meeting IBS diagnostic criteria whose bowel habits cannot be accurately grouped into one of the three main subtypes; this group is uncommon. Difficulty in accurate subtyping can result from frequent changes in diet or medications or an inability to stop medications that affect GI transit. Subtyping should be based on the patient's reported predominant bowel habit on days with abnormal bowel movements. As noted, the BSFS should be used to record stool consistency [124].

Common non-specific symptoms in IBS include abnormal stool frequency, abnormal stool form (BSFS types 1/2 or 6/7), excessive straining during defecation, urgency to defecate, feelings of incomplete evacuation, and mucus with bowel movements. Abdominal bloating is present in most patients with IBS and abdominal distention may be reported, but neither is required for an IBS diagnosis [3].

Serologic tests for celiac disease should be performed in patients with IBS-D or IBS-M who fail empiric therapy. Upper GI endoscopy with duodenal biopsies should be performed if serologic tests for celiac disease are positive or clinical suspicion is high; duodenal biopsies can also identify tropical sprue, another mimic of IBS.

A small subgroup of patients with suspected IBS-D have microscopic colitis. Risk factors for microscopic colitis include age older than 50 years, nocturnal stools, weight loss, shorter duration of diarrhea, recent introduction of new medications, and comorbid autoimmune disease. When colonoscopy is performed in patients with suspected IBS-D, random colon biopsies should be obtained to rule out microscopic colitis [5,126].

Colonoscopy is indicated in the presence of alarm symptoms, family history of colorectal cancer, or persistent diarrhea that has failed empiric therapy. Biopsies of different segments of the colon may be required in patients with chronic diarrhea to rule out microscopic colitis. Colorectal cancer screening colonoscopy is indicated in patients 50 years of age or older (or 45 years of age or older in African Americans) in the absence of warning signs based on national recommendations.

Alarm criteria requiring further testing to rule out organicity include [3,44]:

In addition to consideration of best-available therapeutic options, the following measures can facilitate patient engagement and adherence [44]:

Limited data suggest that IBS symptoms may be improved by lifestyle modifications that include exercise, stress reduction, and good sleep habits [3]. Greater evidence supports dietary interventions.

Increased physical activity in patients with IBS has been found to improve GI symptoms and help protect against symptom deterioration [137]. In one study, exercise for 12 weeks significantly improved symptoms and extra-intestinal manifestations of IBS in 102 patients, while another 12-week exercise trial significantly improved constipation but not other IBS symptoms [137,138]. In adolescent patients with IBS, one hour of yoga daily for four weeks significantly improved symptoms [139].

Other recommendations that may improve IBS symptoms include [118]:

The most common sources of FODMAPs in the western diet are wheat, onions, fruit in which fructose exceeds glucose (e.g., apples, pears), and processed food. Dairy products are important in those with lactose malabsorption.

Self-monitoring is the ongoing, real-time recording of problem behaviors. In IBS, the focus of self-monitoring is internal and external triggers and the thoughts, somatic sensations, and feelings that usually accompany flare-ups. Self-monitoring provides clinically relevant information with which to structure treatment and serves as a useful therapeutic strategy by increasing patient awareness of triggers and contributing factors [55].

In general, TCAs are the first antidepressant choice for pain in non-constipated patients with IBS due to their dual mechanism of action (serotonin and norepinephrine reuptake inhibition). Nortriptyline or desipramine is better tolerated than amitriptyline or imipramine due to fewer anti-histaminergic and anti-cholinergic effects. The usual starting dose is 25–50 mg at night and can be titrated up as needed up to about 150 mg/day, while carefully monitoring side effects and/or blood levels. Typically, lower doses than the full antidepressant dose are effective for visceral pain if no psychiatric comorbidity is present [55].

In 2015, rifaximin was approved by the FDA for the treatment of IBS-D in adults [93]. Clinical trials have demonstrated that rifaximin improved IBS-associated symptoms of bloating, flatulence, stool consistency, and abdominal pain. The drug showed a side-effect profile similar to placebo. Some patients experience relief of IBS symptoms after a course of rifaximin, while others require retreatment at the same dosage [184,186]. Improvement in symptoms relative to placebo showed a gradual reduction over time, but significant improvement persisted for 10 weeks after the treatment course [3]. The usual dosage is 550 mg three times per day for 14 days [93].

Antispasmodic drugs with anticholinergic or calcium-channel blocking mechanisms are used for relieving diarrheal symptoms, abdominal pain and distension, and spasms in all IBS subtypes. However, anticholinergic agents may be better tolerated in patients with IBS-D [5,183]. Otilonium and hyoscine have the best evidence of efficacy, and otilonium bromide is the most effective agent in preventing IBS symptom recurrence. Some patients with IBS have an exaggerated gastrocolic reflex that is in part cholinergic-mediated, and spasmolytics may be best suited for postprandial abdominal cramping and loose stools in these patients [5].