Irritable bowel syndrome (IBS) is defined as chronic or recurrent abdominal pain, altered bowel habits, and bloating, with the absence of structural or biochemical abnormalities to explain these symptoms. Irritable bowel syndrome is part of a broader group of disorders known as functional GI disorders. It is the most common GI diagnosis among gastroenterology practices in the United States and is one of the top 10 reasons for visits to primary care physicians. Irritable bowel syndrome is recognized in children, and many patients trace the onset of their symptoms to childhood. Children who have a history of recurrent abdominal pain are at increased risk of irritable bowel syndrome during adolescence and young adulthood.
Irritable bowel syndrome has no identifiable cause, and laboratory testing is unrevealing. Over the last 5 decades, the understanding of irritable bowel syndrome has evolved from a disorder of motor activities in the upper and lower GI tracts to a more integrated understanding of visceral hypersensitivity and brain-gut interaction.
GI motility abnormalities
Studies evaluating the motor response of the colon to meals, pain, and stress suggest a difference between control subjects and patients with irritable bowel syndrome. Pretreatment with anticholinergic medication in irritable bowel syndrome was demonstrated to reduce meal-stimulated pain and diarrhea. The finding of an abnormal, 3-cycle-per-minute, slow-wave activity in the colon of patients with irritable bowel syndrome was not confirmed by other studies and was noted in some individuals without irritable bowel syndrome.
Abnormal small-bowel motility has also been reported by some investigators. Intestinal transit has been demonstrated to be delayed in patients with constipation-predominant irritable bowel syndrome. In contrast, the transit was accelerated in patients with diarrhea-predominant irritable bowel syndrome. Clustered contractions in the duodenum and jejunum and prolonged propagated contractions in the ileum were noted more frequently in patients with irritable bowel syndrome. Small-bowel motility studies have demonstrated more abnormal findings in patients with irritable bowel syndrome in conscious states than during sleep, suggesting that the condition may result in part from CNS input.
Non-GI smooth-muscle abnormalities
Bladder dysfunction was identified in 50% of patients with irritable bowel syndrome and in only 13% of control subjects. One study found patients with irritable bowel syndrome to have a higher incidence of orthostatic hypotension. A clinical study demonstrated a greater reduction of forced expiratory volumes in 1 second (FEV1) induced by methacholine in patients with irritable bowel syndrome than in control subjects.
Most patients with functional disorders appear to have inappropriate perception of physiologic events and altered reflex responses in different gut regions. Patients with irritable bowel syndrome undergoing balloon distension studies of the colorectum demonstrated awareness of distension and pain at pressures and volumes that were significantly lower than in control subjects. The development of chronic hyperalgesia within the GI tract can be explained by the development of hyperexcitability of neurons in the dorsal horn in response to peripheral tissue irritation or to descending influences from the brain stem. Multiple factors are proposed to alter neuroreceptors and afferent spinal neuron functions. These factors include genetic, inflammatory, local nerve mechanical irritation, motility, and psychological factors.
The brain-gut axis is a bidirectional pathway that links higher cortical centers with visceral afferent sensation and intestinal motor function. Regulation of these connections occurs via numerous neurotransmitters found in the brain and gut, including cholecystokinin, vasoactive intestinal peptide, substance P, serotonin (5-hydroxytryptamine [5-HT]), and many others. These transmitters act at different sites in the brain and gut and lead to varied effects on gastrointestinal motility, pain control, emotional behavior, and immunity.
Serotonin plays a critical role in the regulation of GI motility, secretion, and sensation. In the GI tract, 5-HT is synthesized by the enterochromaffin cells (EC) located within the mucosa of the intestine. 5-HT released by EC cells initiates peristaltic and secretory reflexes by acting on its receptors. Several subclasses of 5-HT receptors are differentiated on the basis of structure, molecular mechanism, and function. Excess serotonin is removed by the serotonin transporter (SERT) expressed by intestinal epithelial cells. Studies have shown that irritable bowel syndrome symptoms may be related to imbalance in mucosal 5-HT availability caused by defects in 5-HT production, serotonin receptors, or SERT.
Dysregulation of the brain-gut system is becoming an acceptable theory to explain the functional GI disorders. Furthermore, several studies have hypothesized that specific 5-HT receptor antagonists may be beneficial in irritable bowel syndrome. Numerous newer noninvasive imaging techniques (eg, positron emission tomography, functional MRI) have been applied to assess brain-gut interactions in healthy patients and in those with irritable bowel syndrome.
Several studies suggest that irritable bowel syndrome may have a genetic basis. The genetic theory is based on twin studies as well as familial aggregation of irritable bowel syndrome. Several twin studies have shown a higher concordance rate for irritable bowel syndrome in monozygotic twins than in dizygotic twins. [1, 2, 3, 4] Studies on familial aggregation have found that patients with irritable bowel syndrome are more likely than controls to present positive family history. [5, 6, 7] However, familial and twin aggregation studies cannot exclude the influence of environmental and social learning in the development of irritable bowel syndrome.
In a twin study conducted by Levy et al, the proportion of dizygotic twins with irritable bowel syndrome who have mothers with irritable bowel syndrome was greater than the proportion of dizygotic twins with irritable bowel syndrome who have co-twins with irritable bowel syndrome. The data also revealed that having a mother or a father with irritable bowel syndrome are independent predictors of irritable bowel syndrome status and both are stronger predictors than having a twin with irritable bowel syndrome. 
Several investigators have proposed that irritable bowel syndrome may be associated with select gene polymorphisms, including SERT, alpha-adrenergic receptors, interleukin-10, transforming growth factor, tumor necrosis factor-alpha, and sodium channel. However, the data are limited, and studies have failed to identify a specific irritable bowel syndrome gene. [8, 9, 10]
Psychosocial factors in irritable bowel syndrome
Numerous studies have found an increased prevalence of abnormal psychiatric disorders, including anxiety, major depression, personality disorders, and hysteria, in adult patients with irritable bowel syndrome, especially patients referred to medical facilities. These psychological disturbances are not believed to cause or induce the symptoms of irritable bowel syndrome but are thought to influence the patient's perception of the symptoms and affect the clinical outcome. Stressful events are known to affect GI functions and may lead to exacerbation of symptoms in patients with irritable bowel syndrome.
In addition, antidepressant or antipsychotic therapy is helpful in some patients with irritable bowel syndrome. A meta-analysis has confirmed the relative efficacy of antidepressant medications in irritable bowel syndrome, particularly in predominantly diarrheic patients experiencing severe pain.  Studies have reported an increased frequency of prior sexual or physical abuse in patients with irritable bowel syndrome and other functional GI disorders.
Some studies have proposed that carbohydrate intolerance may produce significant symptoms in patients with irritable bowel syndrome. Ingestion of lactose, sorbitol, or fructose is associated with increased GI symptoms. Likewise, a food allergy may play a minor role in triggering or exacerbating symptoms in some patients with irritable bowel syndrome. A study by Atkinson et al has shown that immunoglobulin (Ig)G food antibodies may have a role in irritable bowel syndrome and food elimination based on IgG antibodies may be effective in reducing irritable bowel syndrome symptoms. 
GI infection and irritable bowel syndrome
Some investigations found a correlation between the development of irritable bowel syndrome and a prior severe GI infection, especially in patients with higher scores for anxiety.  Symptoms compatible with irritable bowel syndrome affect 10-15% of adult patients after acute infectious gastroenteritis. Factors that increase risk to develop post infectious irritable bowel syndrome include severe and prolonged infection, female sex, younger age, antibiotic treatment for this infection, and concomitant presence of anxiety.
In one pediatric study, 36% of children with prior history of acute bacterial gastroenteritis developed abdominal pain symptoms that were consistent with functional GI disorders. Symptoms were compatible with irritable bowel syndrome in 87% and with dyspepsia in 24%. 
Studies have demonstrated low-grade lymphocytic infiltration in the intestinal mucosa, increased permeability, and increases in inflammatory components including EC and mast cells.
Some studies have shown that small intestinal bacterial overgrowth is common in subjects with irritable bowel syndrome. A double-blind placebo-controlled study by Pimentel et al (2003) showed that normalization of lactulose breath testing with neomycin correlated with symptom improvement in patients with irritable bowel syndrome. 
Symptoms consistent with irritable bowel syndrome are present in 10-20% of adolescents and adults. Less than one third of patients seek medical advice. In the pediatric population, irritable bowel syndrome symptoms are reported in 14% of high-school students and 6% of middle-school students. One third of patients with irritable bowel syndrome trace their symptoms to childhood.
Prevalence in developing countries is probably lower than in Western countries, but this may be explained by a combination of reduced availability of medical care and different cultural approaches to illness.
Irritable bowel syndrome is not a life-threatening condition but can have a serious impact on a patient's daily activities and quality of life. Greater impairments in quality of life are reported in patients with irritable bowel syndrome who sought medical care compared with those who did not consult their physicians for irritable bowel syndrome symptoms. It is a major cause of absenteeism at the workplace and at school. Abdominal pain in patients with irritable bowel syndrome is responsible for significant school absences in 4-5% of middle and high-school students.
Irritable bowel syndrome is not well characterized outside Western countries. According to reported studies, the disease prevalence is lower in Hispanic and Asian populations than in Caucasian populations, and whites are more likely to have irritable bowel syndrome than blacks.
Women are 2-3 times more likely than men to have irritable bowel syndrome. In pediatric patients, both sexes are equally affected.
Irritable bowel syndrome is a disorder of young people. One half of patients experience symptom onset when younger than 35 years, and 40% of patients are aged 35-50 years when symptoms begin. Irritable bowel syndrome is recognized in children. Symptoms consistent with irritable bowel syndrome are reported in 16% of students aged 11-17 years. Irritable bowel syndrome is not described in preschool-aged and younger children because the diagnosis depends on the child's ability to report detailed symptoms.
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