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1 Digestive and Liver Disease 41 (2009) Contents lists available at ScienceDirect Digestive and Liver Disease journal homepage: Mini-Symposium Irritable bowel syndrome: Novel views on the epidemiology and potential risk factors E. Rey a,b, N.J. Talley a,c, a Division of Gastroenterology, Mayo Clinic College of Medicine, Rochester, MN, USA b Division of Gastroenterology, Hospital Clinico San Carlos, Complutense University, Madrid, Spain c Division of Gastroenterology, Mayo Clinic College of Medicine, Jacksonville, FL, USA article info abstract Article history: Received 30 June 2009 Accepted 4 July 2009 Available online 8 August 2009 Keywords: Irritable bowel syndrome Functional bowel diseases Risk factors Symptoms consistent with the irritable bowel syndrome are remarkably frequent around the world. Irritable bowel syndrome prevalence ranges from 2.1% to 22%, depending on criteria used. Women are more frequently affected than men, but the reasons remain obscure; irritable bowel syndrome occurs in all age groups but there appears to be a modest decline in prevalence with advancing age again for unknown reasons. The incidence of irritable bowel syndrome per year has been estimated at approximately 1.5% in community subjects; annually only 0.2% of population will be diagnosed with irritable bowel syndrome. The natural history of irritable bowel syndrome is characterized by symptomatic flare ups and by a high rate of transition to other functional gastrointestinal diseases over the long term. Well recognized risk factors for irritable bowel syndrome include psychological distress and gastroenteritis. However, the association of psychological distress in some cases may reflect confounding factors and might be explained at least in part by cytokine production. Familial aggregation of irritable bowel syndrome occurs, and while the environment is key, twin studies generally support a genetic component in irritable bowel syndrome explaining up to 20% of the variability. Prior surgery may increase risk of irritable bowel syndrome. Early childhood trauma may be important; a low birth weight, nasogastric suction at birth, childhood abuse, and low socioeconomic status may carry an increased risk of suffering with irritable bowel syndrome as an adult. The role of diet remains uncertain but under-studied Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. 1. Introduction The irritable bowel syndrome (IBS) is a clinical syndrome characterized by chronic abdominal pain or discomfort associated with a change in bowel habit, that cannot be explained by any organic or biochemical abnormality [1]. The first description of IBS is attributed to Powell in 1818 [2], and until recently IBS was considered a diagnosis of exclusion [3]. Many experts now believe, though, that a diagnosis of IBS can be made positively based on specific symptom criteria. The current criteria were derived from research in the United Kingdom (resulting in the Manning criteria in 1978) [4], and consecutive refinements of the criteria based on consensus have been published over the past 15 years (from Rome [5,6] to Rome I [7], RomeII[8], and most recently Rome III [9]). The relevance of the criteria in clinical prac- Grant support: Dr Enrique Rey is supported by a grant BA08/90038 from the Carlos III Institute, Ministry of Health, Spain. Corresponding author at: Department of Internal Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32082, USA. Tel.: ; fax: address: Talley.Nicholas@mayo.edu (N.J. Talley). tice, however, is still unclear. A poor agreement between clinical diagnosis and the Rome criteria has been reported [10]; while this may be explained in part by a lack of knowledge of the criteria among physicians [11], it may also be due to a perception of their low clinical utility. The creation of diagnostic criteria by consensus has contributed, without any doubt, to our understanding of IBS, including more in depth knowledge of the epidemiology and risk factors. Today, it remains unknown which definition is optimal but over time the field needs to move to scientifically rigorous criteria that are stable over time, can separate minor irrelevant symptoms from those with a true impact on the subject, and are clinically meaningful to patients [12]. 2. Prevalence The prevalence of IBS varies considerably depending on the criteria applied; most studies rely on the Manning criteria, or one of the successive Rome definitions. Moreover, geography may need to be taken into account since traditionally IBS has been labeled as a disorder of civilization [13]. Considering population-based studies, the prevalence of IBS according to the Manning criteria /$ Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi: /j.dld

2 Table 1 Prevalence of IBS worldwide (population-based studies). Author (year, county) Study population Method questionnaire N (response rate) Criteria for IBS Prevalence F:M ratio Subtypes IBS-C IBS-D IBS-A North America Talley et al. (1991, US) [14] Olmsted County, MN residents yo Mail BDQ 1,021 (82%) Manning 2 17% 1.2 Manning % Manning 4 8.7% Drossman et al. (1993, US) [29] US householder marketing database Mail Ad hoc Q (Validation NS) Hahn et al. (1997, US) [15] NIHS Face-to-face Ad hoc Q Saito et al. (2000, US) [16] Thompson et al. (2002, Canada) [30] Olmsted County, MN residents yo Random phone sample; Canada Hungin et al. (2005, US) [17] Random phone sample Phone Ad hoc Q Andrews et al. (2005, US) [33] Halder et al. (2007, US) [34] Household marketing panel (18 65 yr) Olmsted County residents; survey ) 8,250 (66%) Rome I 9.4% ,392 (NS) Manning 2 8% Rome 3% Mail BDQ 892 (72%) Manning 2 20% 1.2 Manning 3 16% Manning 4 9% Rome 8% Rome II 4.7% Phone Rome II 10,613 (11%) Rome I 13.5% Rome II 12.1% ,000 (35.8%) Manning % % 22% 63% Rome I 7.8% Rome II 6.7% Web Ad hoc Q (Validation 31,829 (82%) Rome II 6.6% % 53.9% 26.1% NS) BDQ 5,027 (58%) Rome II (modified) 11.4% % 57.6% 14.2% Europe Heaton et al. (1992, UK) [31] Family physician patients Face-to-face Ad hoc Q 2,633 (72%) Roma % 2.6 registry (East Bristol) Jones et al. (1992, UK) [18] Family physician patients Mail Ad hoc Q 1,620 (71%) Manning % 1.3 registry (Southern England) Agreus et al. (1995, Sweden) [19] Population-based Mail Ad hoc Q 1,290 (90%) Manning % (municipality of Osthammar, Sweden, born between 1909 and 1979) (modified) Kennedy et al. (1998, UK) [20] Family physician patients Mail Ad hoc Q 4,415 (72%) Manning % 2.2 registry (Northern Region Research Network, yo) Boekema et al. (2001, Netherlands) [21] Phone directory of Utrecht Phone BDQ 500 (85.4%) Manning 2 5.8% 2.5 Mearin et al. (2001, Spain) [22] Representative of national population Face-to-face Ad hoc Q 2,000 (NS) Manning % 2.6 E. Rey, N.J. Talley / Digestive and Liver Disease 41 (2009)

3 Table 1 (Continued ) Author (year, county) Study population Method questionnaire N (response rate) Criteria for IBS Prevalence F:M ratio Subtypes Hungin et al. (2003, Multinational) [23] Phone directory of UK, France, Germany, Spain, Italy, Holland, Belgium, Switzerland Phone Ad hoc Q (validated) Rome I 12.1% 2.3 Rome II 3.3% ,750 (36%) Manning 6.5% Rome I 4.2% Rome II 2.9% IBS-C IBS-D IBS-A Wilson et al. (2004, UK) [35] Family physician patients Mail RIQ 8,346 (62%) Rome II 8.1% % 25.4% 46.7% registry (Birmingham) Bommelaer et al. (2004, France) [24] National phone directory Phone Ad hoc Q 8,221 (NS) Manning % 1.8 Rome I 2.10% Rome II 1.10% Hillila et al. (2004, Finland) [25] Finish residents yo Mail RIQ 5,000 (73%) Manning % 1.5 Rome I 5.5% Rome II 5.1% Dapoigny et al. (2004, France) [36] Representative of national Mail Ad hoc Q (Validation 20,000 (75.6%) Rome II 4.7% 1.5 population NS) Papatheodoritis et al. (2005, Greece) [26] Population-based Face-to-face Modified 756 (92.6%) Manning % (residents in Athens-Piraeus area 15 yo or older) GSRS (modified) Vandvik et al. (2006, Norwey) [37] Population-based (Residents in Oppland and Hedmark Counties born in 1925, 1940, 1955, 1960, 1970) Mail Modified RIQ 11,078 (42%) Rome II 8.1% % 23% 53% Australia Talley et al. (1997, Australia) [27] Barbezat et al. (2002, New Zealand) [28] Electoral list of Penrith, Sydney Birth cohort (born in Dunedin during ) Mail BDQ 1,135 (64%) Manning 2 13% Rome I 12% Mail BDQ 1,021 (96%) Manning % 1.5 Manning % 1.6 Manning 4 3.3% E. Rey, N.J. Talley / Digestive and Liver Disease 41 (2009) Boyce et al. (2006, Australia) [32] Electoral roll of Penrith > 18 yo Mail BDQ 1,225 (62.2%) Rome I 4.4% 3.1 Rome II 8.9% 1.4 Asia Ho et al. (1998, Singapore) [38] Electoral roll of Jurong > 21 Face-to-face BDQ 756 (93%) Manning 2 2.3% yo Masud et al. (2001, Bangladesh) [41] Two villages; all Face-to-face Ad hoc 2,542 (95%) Rome I 8.5% 1.8 residents > 14 yo) (validation NS) Lau et al. (2002, Hong Kong) [42] Two housing blocks > 18 yo Face-to-face Ad hoc (validation NS) 1,984 (65%) Rome II 3.7% 1.1 Kwan et al. (2002, Hong Kong) [43] Phone directory Phone RIQ (validated) 1,000 (56%) Rome II 6.6% 17% 27% 56%

4 E. Rey, N.J. Talley / Digestive and Liver Disease 41 (2009) ,000 (78.2%) Manning 2 11% % 12.8% 2% Face-to-face BDQ Gwee et al. (2004, Singapore) [39] Random sample of all household units Rome I 10.4% 1.3 Rome II 8.6% 1,2 10.9% 9.8% 72.5% 4,264 (98%) Manning % 1.3 Face-to-face BDQ Xiong et al. (2004, China) [40] Cluster sampling of residents in Guangzhou and Huizhou Rome II 5.7% % 74.1% 10.8% 5,492 (86.7%) Rome II 7.1% Face-to-face RIQ Amra et al. (2005, Iran) [44] Random blocks in Shahrekord urban area. Residents > 20 yo 1,900 (93%) Rome II 6.3% % 36% 11.7% Face-to-face Ad hoc Celebi et al. (2004, Turkey) [45] Primary care patients registry in Elizig > 17 yo 3,000 (NS) Rome II 10% % 48.9% 13% Face-to-face RIQ Yilmaz et al. (2005, Anatolia, Turkey) [46] Four provinces (cumulative groups sampling) Phone RIQ 4,230 (25.2%) Rome II 6.6% % 32.8% 42.8.% Han et al. (2006, Korea) [48] Phone directory. Age yo Phone RIQ 1,839 (54%) Rome II 2.9% 2,1 55.2% 31% 13.8% Sperber et al. (2007, Israel) [47] Database representative of population Rome III 11.4% % 15.89% 47.4% 988 (89%) Rome II 13.3% % 29.3% 20.3% Face-to-face RIQ Hussain et al. (2008, Pakistan) [50] Electoral roll of Arafat town, yo BDQ = Talley Bowel Disease Questionnaire or a derivative of this instrument; RIQ = Rome II Integrative Questionnaire; NS = not stated. When BDQ and RIQ were not use in its original English version, Validated indicates some local validation, not just translation. is 8 20% in North America [14 17] and % in other western countries [18 28]. According to Rome I the prevalence is lower, ranging from 7.8% to 13% [15 17,29,30] in North America and 2% to 13% [22 25,27,31,32] elsewhere. Based on the Rome II definition, the prevalence rates vary from 4.7% to 11.4% [16,17,30,33,34] and 1% to 8% [22 25,32,35 37], respectively. Studies in Asia, applying the same criteria reported figures of % with Manning [38 40], % with Rome I [39,41] and % with Rome II [39,40,42 47] (Table 1). There are no population-based studies in Africa and South America. The prevalence of subgroups of IBS (e.g. constipation vs. diarrhea) is controversial, in part due to the criteria applied. Diarrhea-predominant IBS currently accounts for 50% of IBS subjects in North America [34], while in European countries the alternators/mixed subgroup seems to be the most frequent [37].In Asian surveys, there has been high heterogeneity in the distribution of subgroups among the various studies [39,40,43,45 48]. The severity of IBS has not been evaluated in the community, mostly because inherent difficulties in assessing this issue [49]. Moreover, data on the proportion of IBS community subjects reporting severe pain is scarce and surprisingly discrepant; for example, 44% of IBS subjects reported severe abdominal pain in Finland [25], compared with just 4% in Norway [37], according to the results of two population-based studies defining IBS by Rome II criteria. 3. Incidence The calculation of the incidence of IBS is based on repeated surveys in population-based samples, but the follow up intervals have been variable. Due to the fluctuating nature of symptoms, it is difficult to discriminate truly incident cases from cases representing just a flare up of the disease, especially in studies with only a short follow up. Studies providing an estimation of the onset of symptoms of IBS over short periods of time reported 0.2% at 3 months [19],8% at 1 year [51] and 3.5% at 15 months [52]. The longer term studies are more interesting. Halder et al. reported that 16% of subjects without IBS developed IBS at 12 years of follow up [34]. Similarly, Ford et al. observed that 15% of 3659 subjects developed IBS over 10 years follow up [53]. Taking into account these two last studies, we may estimate a linear incidence of around 1.5% per year in the community. The major risk factors identified for the development of IBS were female gender [34,53], somatisation [34] and suffering with dyspepsia at baseline [53]. Two studies have reported data on the incidence of diagnosed IBS. Locke et al. estimated the incidence of physician diagnosed IBS to be 2 cases per 1000 inhabitants per year in Olmsted County, and this was associated with advancing age and female gender [54]. Similarly, the reported incidence in primary care in the UK of IBS was 2.6 per 1000 person-years [55]. 4. Natural history IBS symptoms characteristically fluctuate over time, with flare ups alternating with periods free of symptoms. It has been noted that even over a period of time as short as 2.5 months symptoms can disappear [56]; a rate of 38 50% for IBS symptoms disappearance has been reported at 1 year [19,51] and 33 55% at 10 years [34,53]. It should be noted that disappearance of IBS symptoms does not necessarily mean subjects become asymptomatic. In fact, although 55% of IBS community subjects did not meet criteria for IBS at 12 years of follow up, 44% of them continued to report some form of functional gastrointestinal disease [34]. Predominant bowel habit appears to be unstable over time in patients with IBS; predominant bowel habit changes in 40% [57] to 75% [58] when followed for 1 year, although transition from diar-

5 776 E. Rey, N.J. Talley / Digestive and Liver Disease 41 (2009) rhea IBS to constipation IBS or vice versa is uncommon. Data on community subjects with IBS are scarce, but the transition between diarrhea and constipation predominant IBS may also be infrequent, even after 12 years of follow up [34]. One of the main concerns of patients with IBS is could there be a risk of developing organic disease, especially cancer or inflammatory bowel disease (IBD). Survival of subjects with IBS is the same as expected for the general population and a higher incidence of organic disease has not been observed [59]. In a large UK database, IBS patients had a 1% possibility of being later diagnosed with cancer and 0.6% of being diagnosed with IBD, similar to the non-ibs subjects [55]. Moreover, the a priori risk of organic disease is generally not higher in IBS patients compared to the general population, with the possible exception of celiac disease [60]. 5. Health seeking behavior IBS subjects do not always consult a physician because of their symptoms, and in fact studies done in the 1980s and 1990s showed than less than 60% of community subjects with IBS had ever consulted because of them [61,62]; only 9 33% of community subjects reported a consultation in the prior year [14,18,63]. However, more recent studies have suggested higher rates of consultation, with more than 60% of subjects having consulted ever [27,37] and 30 70% having done so in the prior year [25,27,33,35,64]. Despite the variability, likely depending on cultural factors and regional differences in the accessibility to health care, it seems that the rate of consultation for IBS may have risen perhaps because of increased public awareness of the condition. Four groups of factors have been reported to influence heath care seeking: demographic, IBS symptoms, associated symptoms, and psychosocial factors [65]. Female gender and increasing age are associated with higher consultation rates in most studies in both western and developing countries [25,27,43,53], although not all agree [31]. No association with socioeconomic class or education has been reported in most studies [25,53]. Severity of IBS has been found to be the best predictor of health care seeking in community IBS subjects [27], including severity of pain [25,66,67] and the number of IBS symptoms [31]. However, severity only partly explains why a person decides to consult [14] and a more complex model for seeking behavior has been proposed [65]. In addition to abdominal symptoms, other symptoms, such as blood in stools from straining [66] or the coexistence of nondigestive symptoms [61], may influence health care seeking. Psychological factors have been deemed as the leading factor driving health care seeking since the late-1980s [68 70], and a recent non-population-based study supports this view [71]. However, a large population-based nested case control study showed that psychological factors were associated with the disease rather than with consultation [72] and similarly psychological factors were not found to be predictors of health care seeking in a populationbased study in Australia. [27] Psychological factors might promote consulting because of increased concerns about the meaning of symptoms [66,73] but, when community subjects are studied, such concerns appear to be a feature of the disease and not of those who consult [74]. IBS subjects who consult tend to also seek heath care for other complaints [70,75], and so psychological factors may be more related to consultation for any complaint and not just because of IBS [27]. 6. Age, gender and ethnicity IBS is more frequent in females than males, although a few studies failed to find differences in the prevalence among males and females [40,42]. The female:male ratio ranges between 1.2 and 3.1 in western countries and 0.8 and 2.1 in developing countries. Due to a higher tendency to consult among women, the ratio in primary care offices is around 3:1 [76], and up to 4:1 in tertiary care [77]. Although some differences in symptoms between males and females have been observed, they are not sufficient to justify the proposal of different criteria for IBS by gender [77]. IBS is frequent in all age groups, including children [67] and teenagers [67,78]. A slightly lower prevalence in people older than 65 was found in a population-based survey in Olmsted County [79]; however, the proportion whose symptoms begun in the preceding year was 23% among subjects older than 60, compared to 10% among those younger than 60 years [63]. The association between IBS and ethnicity is difficult to unravel. Population-based studies coming from different geographical areas cannot be directly compared. Several studies do not show differences in racial groups living in the same area [38,80,81]. However, a recent population-based study in Jackson, Mississippi, reported a 2.5 higher prevalence in Whites compared to Africans Americans, adjusting for socioeconomic variables [82]. 7. Comorbidities and surgery IBS subjects frequently report symptoms or diseases that appear unrelated to the bowel, including other gastrointestinal, extraintestinal or psychiatric disorders [83,84]. Several hypotheses have been proposed to explain the co-occurrence of these diseases (central sensitization syndromes, neuroendocrine-immune dysfunction, cytokine secretion, somatisation disorders, biopsychosocial model), but none of them has been firmly established [85] Overlap with other FGIDs IBS frequently overlaps with other FGIDs. A high prevalence of dyspepsia among subjects with IBS in population-based studies has long been recognized [19,86]. The overlap among other FGIDs is also impressive, involving all disorders; when they are evaluated in the community, just one-third of IBS subjects do not reported symptoms of dyspepsia or reflux [87]. Moreover, over 12 years follow up in 865 community subjects showed that the natural course of FGIDs is to change from one to another; for example, only 40% of the subjects with IBS still met the criteria for IBS and 20% became asymptomatic, while another 40% were still symptomatic, but classified as another FGID [34]. The ultimate reason for these transitions between FGIDs is unclear, but taken together, the substantial overlap both in the cross-sectional and longitudinal perspective is a clear indication that they share strong common pathophysiological factors Gastroesophageal reflux disease Among patients with GERD, 30 70% have been found to suffer from IBS; similarly, among patients with IBS, GERD is diagnosed in 17 79% [88]. The overlap between IBS and GERD was confirmed by a population-based study, which showed that despite the high prevalence on both conditions in the community, they occur together more than expected by chance [89]; reasons for the overlap are unclear, but somatisation was shown to be a risk factor for the association of IBS with GERD [89] Psychiatric illness The association between psychiatric disorders has been long recognized, with depression being the most common. IBS was identified in 25 30% of patients with major depression in two studies, a

6 E. Rey, N.J. Talley / Digestive and Liver Disease 41 (2009) higher prevalence than in the control groups [84]; also, 25% of subjects with IBS in tertiary care studies are diagnosed with depressive disorder and additional 30% with anxiety disorders [90]. However, the association of depression and IBS was not found in a community study [91]. Reasons behind the association are currently unknown. Several case control studies have reported a higher prevalence of other psychiatric disorders in patients consulting for IBS [84], including binge eating disorders, panic attacks, and mood disorders, obsessive compulsive [92] and post-traumatic stress disorder Gynecological disease IBS appears to be associated with increased gynecologic problems. In one study, 60% of women with dysmenorrea suffered from IBS compared to only 20% of controls; in addition, IBS was more common among women with dyspareunia. A relationship with urinary symptoms, especially interstitial cystitis, has also been noted [83] Asthma Two population studies have found an association between asthma and IBS [20,44], and notably in a large case control study, asthma patients showed a prevalence 20% higher than controls [93]. Although food allergy has been suggested, and GERD might play a role, the mechanism behind the association is still unclear Surgery Several studies, comprehensively reviewed by Hasler and Schoenfeld in 2003 [94], showed that IBS subjects are more likely that non-ibs subjects to have undergone a hysterectomy, cholecystectomy, appendectomy or pelvic surgery. Two recent longitudinal studies provide new insights into this issue. In a large populationbased study in Olmsted County, with 10 years follow up, higher rates of cholecystectomy were not identified among subjects with IBS, suggesting that results from cross-sectional studies may be biased [95]. However, a longitudinal population-based study in Italy, with 7 years follow up, reported a higher risk of cholecystectomy among subjects with IBS, suggesting that inappropriate surgical indication may be the underlying reason [96]. These discrepancies are likely explained by the standard of medical care provided to the populations assessed and by differing medical attitudes. An alternative explanation is that surgeries per se represent a risk factor for the onset of IBS. A prospective study reported a 10% incidence of IBS, mostly constipation predominant IBS, 6 months after hysterectomy [97]. A population-based survey showed that IBS symptoms are reported more frequently by women who underwent a hysterectomy (a mean of 11 year before), and also, to a lesser extent by subjects who underwent a cholecystectomy (a mean of 7 years before) [98]. Another population-based longitudinal study supports the possibility than cholecystectomy is a risk factor for developing IBS [95]. 8. Risk factors Over the past few decades, several risk factors have been identified for IBS through case control- and community-based studies. Difficulty in separating out factors promoting health care seeking from those actually related to IBS has handicapped identifying true risk factors for the disease. The relative importance of each factor is evolving, and currently we may view IBS as a disease in which several factors can interact along the whole life of the subject, from the genetic background to daily life experiences. Gastroenteritis in the adulthood, a well recognized risk factor for IBS, will not be further discussed, since it will be extensively reviewed elsewhere in this issue Familial aggregation Familial aggregation of IBS has been shown in population-based studies. Recently, Saito et al. [99] confirmed aggregation of IBS in families where the IBS status of the relatives was directly collected from them; the rate of IBS among relatives of subjects with IBS were threefold higher than among relatives of the controls. From twin studies, the genetic contribution to IBS has been estimated to be up to 20%[100]. The twin research further suggests that IBS is mostly the result of the contribution of individual environmental factors and genetic factors [100]. Searching for an IBS gene is the challenge for the next decade. Several candidate genes have been proposed, but no definitive associations have been established [100] Early life events Events occurring early in life have emerged as potentially relevant factors. Several studies have shown that a history of FGID carries an increased odds for IBS as an adult of around 2 [101]. In a population-based study [102], IBS in adulthood was associated with chronic abdominal pain in childhood, specifically between 7 and 9 years of age, independent of maternal emotional distress or psychiatric co-morbidity in adulthood. External events during infancy and childhood may also lead to IBS as adults. Studies suggest that high socioeconomic class during childhood, using as proxy the number of person per room [103] or the socioeconomic class of parents [102,104]. However, one study failed to find an association with socioeconomic class at birth [105] and it is in contrast with the potential influence of adult socioeconomic status on the onset of IBS; Ford et al. [53] found that lower socioeconomic class as an adult was associated with a higher probability of the onset of IBS in a 12 year follow up of adults. Very early traumatic events in life have been related to IBS. Low weight at birth (less than 1.5 kg) revealed an increased risk of IBS of over two in a twin study [106], and the use of nasogastric suction at birth was associated with an odds ratio of three for suffering an FGID in adulthood [107] Diet Many patients report that food precipitates or aggravates their symptoms, and this has also been shown in community subjects with IBS [108]. Only one population-based study evaluated diet in IBS; the results suggested that food sensitivity rather than different diet composition may be related to IBS [109] Psychosocial factors and abuse Psychological factors have long been recognized to be associated with IBS and several population-based studies have shown that IBS is linked to psychosocial factors independent of health care consultation [27,72, ]. Although differences between IBS and controls among several personality traits have been reported, there is not a unique profile associated with IBS [113]. Higher level of neuroticism has been uniformly reported, denoting than IBS subjects are more prone to develop anxiety and higher degree of stress when facing threatening events [113]. In fact, daily stress has been related to IBS symptoms on a daily basis [113]. Somatisation, the tendency to report excess somatic symptoms is a risk factor for developing

7 778 E. Rey, N.J. Talley / Digestive and Liver Disease 41 (2009) IBS [34,52], and has been related to more severe IBS in patients [114]. Increased serum levels of several pro-inflammatory cytokines have been reported in IBS patients [115,116] and levels of IL-6 were found to correlate with anxiety in them [116]; currently it is unclear the direction of such a relationship, but it is conceivable that proinflammatory cytokines activate the hypothalamic pituitary axis [115], which would modulate psychological symptoms. Among traumatic events, abuse has long been recognized to be a factor associated with IBS. Abuse in childhood, particularly sexual abuse, has been linked to IBS in the general population [117] and patient populations [118], although it was not found uniformly in all community studies [110,119]. A history of abuse in adulthood has been associated with IBS in population-based studies [118,119], and on-going abuse also appears to be important [120]. 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