Functional gastrointestinal disorders (FGIDs), represented by functional dyspepsia (FD) and irritable bowel syndrome (IBS), are a group of disorders that include variable combinations of chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities. FGIDs account for a significant percentage of patients seen in primary care settings with abdominal symptoms. Although the definition of FGIDs can easily affect the prevalence, the prevalences of dyspepsia/FD and IBS diagnosed by the Rome III criteria in the general population are 5.3?20.4% and 1.1?29.2%, respectively. Recent reports of FD and IBS defined by the Rome III criteria indicated a female predominance. Regarding the subtype prevalence of FD, postprandial distress syndrome was more prevalent than epigastric pain syndrome (5.6?13.9% vs 0.9?9.5%). The subtype prevalence of IBS is characterized by male predominance for IBS with diarrhea and female predominance for IBS with constipation. Factors affecting the development of FGIDs such as epidemiological factors including genetic and environmental factors, are important. Gene polymorphisms are involved in the development of FGIDs. The prevalence differs among races and geographic areas. Foods may affect the development of FGIDs, but the causal relationships between food and FGIDs are not conclusive. The symptoms often regress and appear in the course of these entities. Building a favorable patient-doctor relationship is effective for controlling symptoms of FGIDs. Physicians should explain that FGIDs are highly prevalent conditions, impair the patients’ quality of life even without evident underlying organic causes and are not life-threatening conditions to ensure patients’ understanding.
Functional gastrointestinal disorders (FGIDs) are a group of gastrointestinal (GI) disorders that include various combinations of chronic or recurrent GI symptoms not explained by structural or biochemical abnormalities.1 Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are among the most widely recognized FGIDs. It is characteristic of the FGIDs that each entity has no specific objective findings, and that they overlap with each other. Therefore, these entities are syndromes, and their diagnosis and treatment are similar. Diagnosis of FGIDs is based on patients’ self-reported symptoms. Therefore, the definition of the symptoms may differ by countries and geographic areas. The pathophysiology of FGIDs is recently becoming clearer. The definition and the diagnostic criteria have been revised, and the diagnostic system is becoming more systematic.1,2 In this review, the epidemiology of FGIDs in Japan and in the world is reviewed.
It is well-known that dyspeptic symptoms occur with organic diseases such as reflux esophagitis, gastroduodenal ulcer, and cancer. However, dyspepsia without organic disease is more prevalent in patients who seek medical care.3 El-Serag et al4 performed a meta-analysis of the literature published between 1976 and 2000 that showed the frequency of dyspepsia to be 10?40%; however, this frequency was 5?12% when concurrent symptoms including heartburn were excluded. In the Rome II definition published in 1999,2 reflux symptoms were excluded from the definition of FD, and when IBS symptoms were present, FD was diagnosed as IBS. Therefore, whether heartburn or IBS is included easily affects the prevalence of FD. Kawamura et al5 reported that the prevalence of FD defined by Rome II in subjects undergoing a health check-up was 13% when organic diseases were excluded. Shaib et al6 also reported that the prevalence of FD was 15% when organic diseases were excluded by endoscopy and when subjects with gastroesophageal reflux disease symptoms were excluded. In a report from England, when endoscopy was performed in 20% of patients to exclude organic diseases, the prevalence of FD was thought to be 11.5%.7 In a report from Norway, when endoscopy was performed in almost all patients, the prevalence of FD was 14.7%.8
The prevalence of uninvestigated dyspepsia or FD in the general population, diagnosed by Rome III criteria, which has been used from 2006, has been reported to be 5.3?20.4% (Table 1).9?22 Hongo et al23 reported that organic lesions were found in only 9% of patients examined by endoscopy because of dyspepsia symptoms. Furthermore, among those without any specific lesions detected on endoscopy, GI symptoms were resolved within one week after the endoscopy in 28% of patients before initiating medication. Okumura et al3 reported that 21% of patients who visited a university hospital with abdominal symptoms had FD.
We also recently performed an Internet survey using a registered panel in Japan to elucidate the prevalence of dyspepsia and childhood abuse history in the population.24 When we estimated the prevalence of dyspepsia using our age-stratified subjects’ data and the Japanese population census ( http://www.stat.go.jp/english/data/kokusei/index.htm), the prevalence of dyspepsia in Japan was estimated to be 21.9%, and the percentage of subjects who consulted a medical institute was only 5.7% of the Japanese population.25 In other words, only one-fourth of dyspeptic subjects visited a medical institute. As the usefulness of an Internet survey was not validated, these conclusions are not firm. With the recent advances of Internet applications, online surveys may be useful as a tool to estimate the prevalence, especially in the general population.
IBS is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit and with features of disordered defecation.26 In a systematic review of IBS in North America, the prevalence of IBS ranged from 3% to 20%, with most estimates ranging from 10% to 15%.27 Reports from Japan indicated that the prevalence of IBS defined by Rome II was 6.1% to 35.5%. In reports using Rome III criteria, the prevalence of IBS was 1.1% to 29.2% (Table 2).11,12, 14,15,18,21,22,28?38 Miwa29 reported that the prevalence of IBS was 13.1% (male 10.7% and female 15.5%), and when the prevalence of IBS was evaluated using Rome II criteria in the same cohort, IBS prevalence was 9.8%, suggesting that the Rome III criteria are better for picking up more masked IBS cases.
The prevalences of FGIDs other than FD and IBS in the general population were investigated in few studies. Only two reports investigated the prevalence of functional bowel disorders, including functional abdominal bloating, functional constipation (FC), functional diarrhea, unspecified functional bowel disorder (UFBD), and functional abdominal pain syndrome (FAPS) defined by Rome III criteria (Table 3).14,33 These two reports showed female predominance of FC and UFBD. Among these FGIDs, UFBD, uninvestigated dyspepsia, and FC were common, and FAPS was less common than other FGIDs. This is consistent with a report of hospital outpatients in Japan.39
The investigation environment, the definition of symptom duration, and the accuracy of excluding organic diseases have all been identified as factors affecting the prevalence of FGIDs. In the Rome II definition,2 the symptom duration of FD and IBS was defined as at least 12 weeks during the preceding 12 months, and in Rome III,1 at least 3 months with symptom onset at least 6 months prior to diagnosis, which implies that the duration of symptoms can easily change the prevalence. In Japan, people who have symptoms visit a medical institute within less than 6 months of symptom onset because access to facilities is easy.40,41 Thus, the duration of symptoms does not match the criteria of FD in the majority of cases.40,42 Furthermore, although structural or biochemical disorders should be excluded, they are not easy to exclude in a survey of the general population. In a large-scale analysis of the prevalence of FGIDs, it is not easy to perform examinations of all subjects. In general practice, the availability of examinations may be limited and different compared to those in a large hospital or university hospital. The characteristics of patients are also different in primary care and tertiary care settings. When new patients who visited primary clinics and tertiary care hospitals with gastrointestinal symptoms for more than 6 months in Korea were analyzed, the prevalences of FD and IBS defined by Rome III criteria were 46.0% and 40.2%, respectively.43 On the other hand, when patients who visited a general hospital in Japan were analyzed, the prevalences of FD and IBS defined by Rome III criteria were 2.1% and 2.4%, respectively.39 Therefore, when we evaluate the prevalence of FGIDs, we should take the background characteristics of the analyzed subjects into account.
The prevalence of abdominal symptoms in a population-based study in the USA showed no significant differences between men and women.44 Even in Japan, no difference in the prevalence of non-ulcer dyspepsia has been reported. The definition of dyspepsia may easily affect the prevalence, and the surveys using Rome II or other than Rome definitions mostly showed no differences between men and women in the prevalence of dyspepsia.3,45 However, Schlemper et al46 assessed dyspeptic symptoms present during more than 7 days per 3 months in a working population and reported that, in Japanese men and women, the non-ulcer dyspepsia rates were 11% and 26%, while in The Netherlands, they were 12% and 21%, respectively, indicating that dyspepsia is more prevalent in women. A report from Belgium also showed that female FD was more prevalent in consecutive patients who visited a general gastroenterology outpatient clinic.47 In a population-based study of the Icelandic population, FD was diagnosed in 12.3% of males and 20.2% of females, and it was significantly more common in females.47,48 Furthermore, in a systematic review by Ahlawat et al,49 dyspepsia had a different pattern of symptoms in men and women.49 In this manner, study area, type of survey, and the definition of FD might easily affect the results.
Approximately two-thirds of IBS patients are female, and the prevalence of IBS in females is thought to be 14?24%.50 The potential role of sex hormones in sex differences in the epidemiology of IBS patients has been proposed based on the female predominance, as well as the correlation between IBS symptoms and hormonal status.51 Even in Japanese studies, female predominance has been reported.52,53 Recent reports of FD and IBS defined by Rome III criteria also indicated a female predominance in Japan and other countries (Tables 1 and 2).
Regarding the subtype prevalence of FD defined by Rome II criteria, in Japanese health check-up subjects, dyspeptic symptoms were present in 17%, and approximately 10% of subjects complained of dysmotility-like dyspepsia corresponding to post-prandial distress syndrome (PDS), and approximately 4% of subjects complained of ulcer-like dyspepsia corresponding to epigastric pain syndrome (EPS).54 Even in a recent report using Rome III criteria, PDS was more prevalent than EPS in Sweden, China, and Japan (Table 1).16,17,55 However, a report from Italy indicated that EPS was more prevalent than PDS (Table 1).13 These differences by geographic areas were also reported in a review of dyspepsia defined by Rome II criteria.56 Therefore, considering these epidemiological differences of FD subtypes between Western countries and East Asia, the optimal treatment strategies for FD may differ among countries.
On the other hand, with respect to the subtype prevalence of IBS, IBS with diarrhea (IBS-D) is more predominant than IBS with constipation (IBS-C) (Table 2). The subtype prevalence of IBS is characterized by male predominance in IBS-D and female predominance in IBS-C.52,57 In a meta-analysis, women were at slightly higher risk for IBS than men.58 When the prevalence of IBS and its subtypes was determined using Rome III criteria, the prevalences of IBS subtypes in Japanese were as follows: IBS-D, male 47% and female 17%; IBS-C, male 9% and female 34%; and mixed IBS (IBS-M), male 44% and female 49%.29 IBS is most prevalent in patients 20 to 30 years old, and this prevalence decreases with age.58 In a Japanese study of medical and nursing students, the prevalence of IBS was 35.5%, and students with IBS symptoms were more prone to have anxiety and depression, indicating that stress is involved in the development of IBS symptoms.59 Furthermore, high socioeconomic status may be related to the prevalence of IBS, but this is not conclusive.58
The domestic international gastroenterology surveillance study (DIGEST) investigated the prevalence and economic/quality-of-life impact of uninvestigated dyspepsia over 3 months and found that 41% of the general population had dyspepsia in 7 international sites, 60% in the USA, and 26% in Japan, indicating that the Japanese prevalence is relatively low.60 On the other hand, reports of dyspepsia prevalence in the general population from Australia and China showed that 24.4% and 23.5% had dyspepsia, respectively.61,62 Although these data indicate that the prevalence differs among geographic areas, the studies may not have completely excluded organic diseases, and the definition of symptom frequency was different in the reports. Furthermore, the interpretation of symptoms may be subtly different in countries and geographic areas. As the definition of FGIDs differs in the Rome III criteria, the Rome II criteria, and previous definitions, it is not easy to compare the data directly.
In an analysis performed in the USA, the prevalence of FD was not different by race.6 On the other hand, race may affect the development of IBS. The prevalence of IBS was 13.1% in Caucasians and 7.9% in Africans.63 A meta-analysis of the global prevalence of IBS indicated that the prevalence of IBS varied among countries.58
FD patients do not usually eat their meals 3 times a day, and the intakes of fat, glucose, and vitamin C are less in female FD patients.64 However, it is also reported that the patterns of food and meal intake were not different,65 indicating that the relationship between food and FD is not clear. Since it is not known if the difference in the food intake pattern in controls and FD is the result of attempting to prevent the development of symptoms or the cause of symptoms, further studies are needed to elucidate the causal relationship.
In IBS patients, food may exacerbate symptoms. Milk, wheat, eggs, and foods high in salicylates or amines are identified as causes of exacerbation of IBS symptoms.66 Japanese IBS patients have significantly more irregular meal habits.67 Recent studies from Australia and the United Kingdom (UK) indicated that dietary restriction of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) is effective for the treatment of IBS.68?71 Khan et al72 summarized the clinical efficacy of a low-FODMAP diet in IBS patients. A low-FODMAP diet improved self-assessed satisfaction with stool consistency in both IBS-D and IBS-C subgroups, but not in healthy controls.71 However, further studies are needed to evaluate the mechanisms of these effects. Since the daily diet differs among countries, the efficacy of a low-FODMAP diet should be evaluated in each country.
Lactose intolerance and IBS can occur at the same time in a person, but they are separate conditions that should be treated differently. A recent National Institutes of Health (NIH) conference defined “lactose intolerance as the onset of GI symptoms following a blinded, single-dose challenge of ingested lactose by an individual with lactose malabsorption, which are not observed when the person ingests an indistinguishable placebo.”73 The risk of lactose intolerance is related to the dose of lactose ingested and intestinal gas production and is increased in patients with IBS-D.74 Although it is not easy to exclude lactose intolerance in daily clinical practice, it should not be included in IBS.
After the unveiling of whole human genome sequences in 2004, it became clear in many diseases, including malignant tumors, hypertension, and psychosomatic diseases, that single nucleotide polymorphisms of genes were involved even in drug metabolism. In other words, when a single nucleotide is different, translation of a protein or function can easily be changed, and these changes may affect the development of diseases and treatment effectiveness.
Even in FGIDs, these gene polymorphisms are involved in the development of diseases. Syndromes of FGIDs had been thought to be difficult to explain with gene polymorphisms as the pathophysiology. However, it recently became clear that not only environmental factors, but also genetics are involved in the development of FGIDs.75,76 Levy et al75 analyzed 6060 twin pairs, and concordance for IBS was significantly greater in monozygotic (17.2%) than in dizygotic (8.4%) twins, supporting a genetic contribution to IBS. Even in FD patients, familial aggregations have been identified.77 As the gene polymorphisms that are involved in the development of IBS,
In FD, Holtmann et al85 showed for the first time that
We also analyzed the association between SERT gene (
These data indicate that genetic factors are involved in the development of FGIDs. However, the odds ratio that can be acquired by these polymorphisms is maximally two to three. We need further evaluation of how these genetic factors and other circumstantial factors interact. Environmental factors affect their development. Children of mothers with IBS have more non-GI, as well as GI, symptoms.94 When the parents have IBS, the risk of the development of IBS in their children is high, and the concordance between mothers and children was greater than the concordance between monozygotic twins,75 indicating that not only genetic factors, but also parental behaviors affect their children.95 Childhood abuse is associated with the development and exacerbation of IBS and the development of dyspepsia.24,96?98 These are also environmental factors related to the development of FGIDs.
As for the natural course of FD, the dyspeptic symptoms disappear in 50% of patients after several years.4 Even in IBS patients, 40% of patients are not diagnosed as having IBS one year later.27 Although the prevalences of FD and IBS were stable over 12?20 months, there was considerable turnover, with approximately half of those with FD and IBS on the first survey not having these symptoms on the second survey.99 Another report using Rome II criteria also indicated that the proportion of subjects in a subgroup of IBS remained the same over a year, and more than 75% of subjects changed to either of the other 2 subtypes at least once.100 IBS-M was the least stable diagnosis (only 4.9% remained in the original classification). Transitions between IBS-M and IBS-C were more likely than between IBS-D and IBS-M.
Halder et al101 reported the natural history of FGIDs in a US population. In a prospective cohort followed for 12 years, approximately 20% had the same symptoms among people with symptoms at baseline, 40% had no symptoms, and 40% had different symptoms at follow-up. In uninvestigated dyspepsia, IBS-C, IBS-D, IBS-M, constipation, and diarrhea, the disappearance rate of each FGID between the initial and final surveys was 67%, 60%, 60%, 47%, 78%, and 71%, respectively. The feature that symptoms shift among FGIDs and disappear might also be characteristic of FGIDs.
In a large-scale survey in Japan, the symptoms of FD patients with symptoms at least twice a week regressed in one-third of patients after they were told that they had no organic disease based on examinations including endoscopy and of the pathophysio-logical basis of FD.102 These data indicate that explanation of the condition to patients affects the symptoms of patients with FD, and that building a favorable doctor-patient relationship is effective for controlling symptoms of FD.
It is well-known that FGIDs represent the most prevalent condition in patients who come to medical institutions with abdominal symptoms. Determining the etiology of these patients is important to establish the treatment strategy in the primary care setting.
Although the definitions of FGIDs can easily change their prevalence, there is no doubt that we often see FGID patients in the outpatient clinic. If we do not care for these patients appropriately, physicians and staff cannot establish good relationships with them, and patients will continue with doctor shopping. Regardless of the definition of FGID, physicians should explain the condition and ensure that patients have a satisfactory understanding of their disease.
Prevalence of Fucntional Dyspepsia (Rome III Criteria)
|Study||Sample size||Subject group (Method of data collection)||Country||Age||Prevalence (%)||UD/FD (%)a|
|Aro et al,9 2009||1001||GP (Postal)||Sweden||20?80||20.2||15.7||5.2||12.2||-||-||13.5||26.5|
|Barzkar et al,10 2009||18 180||GP (Interview)||Iran||16?80||8.5||-||-||-||8.3||-||6.1||10.9|
|Kaji et al,11 2010||2680||Health check-up||Japan||mean 40||10.0||-||-||-||14.2||3.4||-||-|
|Noh et al,12 2010||2388||Health check-up||Korea||mean 43||-||8.1||-||-||10.1||-||-||-|
|Zagari et al,13 2010||1033||GP (Postal)||Italy||32?84||15.1||11.0||8.8||6.3||-||-||12.5||17.8|
|Chang et al,14 2012||4275||GP (Interview)||Taiwan||19 ≤||5.3||-||-||-||4.4||0.3||4.4||6.3|
|Choung et al,15 2012||3517||GP (Postal)||USA||mean 61||9.8||-||-||-||19.4||5.2||6.2||12.8|
|Mak et al,16 2012||2011||GP (Telephone)||China||15?65||8.0||-||0.9||6.9||-||-||6.9||8.9|
|Matsuzaki et al,17 2012||8038||GP (Internet)||Japan||20?65||12.8||7.0||2.3||6.2||-||-||6.6||7.3|
|Miwa,18 2012||15 000||GP (Internet)||Japan||20?79||6.5||-||-||-||14.0||3.0||M < F|
|Kim et al,19 2014||3399||Health check-up||Korea||15?98||-||20.4||9.5||13.9||-||-||17.5||24.0|
|Min et al,20 2014||5000||GP (Telephone)||Korea||20?69||7.7||-||4.2||5.6||3.5||1.9||5.9||9.5|
|Perveen et al,21 2014||3000||GP (Interview)||Bangladesh||15?97||8.3||-||6.0||6.8||12.9||3.5||8.7||8.0|
|Rasmussen et al,22 2014||47 090||GP (Internet)||Denmark||20 ≤||7.7||-||-||-||10.5||2.9||6.4||8.8|
aPrevalence in male (M) and female (F) (%), including the calculated data from papers.
UD, uninvestigated dyspepsia; FD, functional dyspepsia; EPS, epigastric pain syndrome; PDS, postprandial distress syndrome; GP, general population; -, not assessed.
Prevalence of Irritable Bowel Syndrome (Rome III Criteria)
|Study||Sample size||Subject group (Method of data collection)||Country||Age||IBS (%)a||Subtype (%)a|
|Jung et al,28 2007||2273||GP (Postal)||USA||33?93||11.1||7.9||13.9||3.2||3.9||1.3||2.7|
|Miwa,29 2008||10 000||GP (Internet)||Japan||20 ≤||13.1||10.7||15.5||3.1||3.9||6.1||-|
|Gomez Alvarez et al,30 2009b||558||GP (Interview)||Colombia||18?60||19.9||-||-||-||-||-||-|
|Khoshkrood-Mansoori et al,||18 180||GP (Interview)||Iran||16 ≤||1.1||0.6||1.5||-||-||-||-|
|Lee et al,32 2009||2005||GP (Telephone)||China||15?65||5.4||4.6||6.2||1.1||2.0||0.3||1.9|
|Kaji et al,11 2010||2680||Health check-up||Japan||Mean 40||14.2||-||-||-||-||-||-|
|Noh et al,12 2010||2388||Health check-up||Korea||Mean 43||10.1||-||-||-||-||-||-|
|Sorouri et al,33 2010||18 180||GP (Interview)||Iran||16?80||1.1||0.6||1.5||-||-||-||-|
|Ebling et al,34 2011||703||GP (Postal)||Croatia||20?69||29.2||21.4||36.7||-||-||-||-|
|Kubo et al,35 2011||2717||Health check-up||Japan||Mean 40||13.5||10.5||19.3||2.9||3.8||3.3||3.6|
|Makharia et al,36 2011||4767||GP (Interview)||India||18?64||4.0||3.2||4.8||0.3||1.5||1.7||0.5|
|Chang et al,14 2012||4275||GP (Interview)||Taiwan||19 ≤||4.4||3.4||5.4||-||-||-||-|
|Choung et al,15 2012||3517||GP (Postal)||USA||Mean 61||19.4||-||-||-||-||-||-|
|Miwa,18 2012||15 000||GP (Internet)||Japan||20?79||14.0||12.7||15.4||-||-||-||-|
|Krogsgaard et al,37 2013||6112||GP (Internet)||Denmark||18?50||16.0||M < F||2.9||5.3||5.7||1.8|
|Lin et al,38 2014||1002||GP (Interview)||UK||16?93||6.0||M < F||0.7||1.4||2.7||1.2|
|Perveen et al,21 2014||3000||GP (Interview)||Bangladesh||15?97||12.9||12.4||13.6||3.5||4.5||3.7||0.6|
|Rasmussen et al,22 2014||47 090||GP (Internet)||Denmark||20 ≤||10.5||7.9||12.8||-||-||-||-|
aIncluding the calculated data from papers,
bSpanish (English abstract).
IBS, irritable bowel syndrome; M, male; F, female; IBS-C, IBS with constipation; IBS-D, IBS with diarrhea IBS-M, mixed IBS; IBS-U, unsubtyped IBS; GP, general population; -, not assessed.
Prevalence of Functional Gastrointestinal Dyspepsia (Rome III Criteria)
|Study||Sample size||Subject group (Method of data collection)||Country||Age||PrevalenceTotal (M/F) (%)|
|Sorouri et al,33 2010||18 180||GP (Interview)||Iran||16?80||8.9(?/?)||1.1(0.6/1.5)||1.5 (1.4/1.7)||2.4 (1.2/3.7)||0.2(0.2/0.3)||5.5(4.3/6.7)||-|
|Chang et al,14 2012||4275||GP (Interview)||Taiwan||19 ≤||5.3 (4.4/6.3)||4.4 (3.4/5.4)||2.1 (1.3/3.0)||4.4 (2.8/6.2)||2.2 (2.7/1.7)||8.9 (7.6 /10.2)||0.4 (0.2/0.5)|
M, male; F, female; UD, uninvestigated dyspepsia; IBS, irritable bowel syndrome; AB, abdominal bloating UBD, unspecified bowel disorder; APS, abdominal pain syndrome; GP, general population; -, not assessed.