Irritable Bowel Syndrome Subgroups Research Articles

Microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a multifactorial disease during which the pathophysiological role of the gut microbiota has been recently highlighted. In almost 20% of the patients, IBS is clearly a post-infectious IBS as a consequence of an acute bacterial gastroenteritis. Some papers have reported an abnormal colonic fermentation in IBS patients that could explain symptoms such as bloating and be one of the factors triggering visceral hypersensitivity. More recently, significant differences in the composition of both the luminal and mucosa-associated microbiota have been reported between both IBS patients and healthy controls and IBS subgroups while some arguments exist for a small intestinal overgrowth in a subset of IBS patients. All these arguments for a deleterious role of the gut microbiota lead to the actual discuss to consider new therapeutic options, including mainly pre- and probiotics and maybe antibiotics.

Stability of the irritable bowel syndrome and subgroups as measured by three diagnostic criteria – a 10‐year follow‐up study

The irritable bowel syndrome (IBS) is a common disorder, but information on its natural history is limited. To study the performance of four IBS criteria in detecting incidence and stability of categories over a 10-year period. This study was a population-based postal study. Questionnaire was mailed to the same age- and gender-stratified random sample of the Icelandic population aged 18-75 years in 1996 and again in 2006. IBS was estimated by the Manning criteria, Rome II, Rome III, subgroups and self-report. Prevalence of IBS varied according to criteria: Manning showed the highest (32%) and Rome II the lowest (5%). Younger subjects and females were more likely to have IBS. Prevalence was stable over 10 years for all criteria except Rome III. There was a turnover in all IBS subgroups and a strong correlation among IBS, functional dyspepsia and heartburn. The prevalence of the IBS remained stable over a 10-year period with a turnover in symptoms. The study suggests that IBS is a cluster of symptoms that float in time between different IBS categories, functional dyspepsia and heartburn. The irritable bowel syndrome in Iceland is very common and indicates a chronic condition, which poses a heavy burden on the health care system.

Intestinal dysbiosis in irritable bowel syndrome: etiological factor or epiphenomenon?

Evaluation of: Lyra A, Rinttilä T, Nikkilä J et al. Diarrhoea-predominant irritable bowel syndrome distinguishable by 16S rRNA gene phylotype quantification. World J. Gastroenterol. 15(47), 5936–5945 (2009).Irritable bowel syndrome (IBS) is a functional disorder of multifactorial origin. Recent interest has been directed to the potential role of intestinal microbiota in the pathophysiology and symptom generation of this syndrome. This hypothesis is supported by the evidence of an infectious trigger in a proportion of patients, the identification of changes in bacterial composition and the detection of antibodies against flagellin, a component of indigenous flora, and by the potential therapeutic modulation of intestinal microbiota with probiotics and nonabsorbable antibiotics in IBS. The study by Lyra et al. assessed fecal microbiota in IBS patients and controls by applying a set of 14 quantitative real-time PCR assays targeting 16S ribosomal RNA gene phylotypes putatively associated with IBS, based on 16S ribosomal RNA gene library sequence analysis. In addition, microbiota composition was investigated over time by applying statistically advanced analyses at three timepoints during 6 months of follow-up. The authors showed that the intestinal flora of patients with diarrhea-predominant IBS diverged significantly not only from controls but also from the other IBS subgroups. The results by Lyra et al. further support the hypothesis that intestinal microbial flora has a role in IBS pathophysiology, and foster the idea that abnormal microbiota may act by triggering local and systemic immune responses linked to symptom generation. Further studies are now needed to clarify the key role of intestinal microbiota (as opposed to a secondary effect) in this common human disease.

Anorectal function and dyssynergic defecation in different subgroups of patients with irritable bowel syndrome

The purpose of this study was to evaluate anorectal function in different subgroups of patients with irritable bowel syndrome (IBS), including those with mixed bowel habits. Sixty-six IBS patients selected according to Rome III criteria (39 female and 27 male patients; mean age, 41.5 +/- 15.4) and 20 subjects in the control group (13 female and 7 male patients; mean age, 41.4 +/- 13.7) were examined. The IBS patients were divided into three subgroups according to bowel movement pattern: patients with constipation (27%), patients with diarrhea (27%), and patients with mixed bowel habits (46%). Anorectal manometry and rectal distension test were performed using a four-lumen water-perfused catheter with a polyethylene balloon. No significant differences in manometric parameters between the subgroups of IBS patients and the control group were found, except for pelvic floor dyssynergia (PFD), which was more frequent in all subgroups of IBS (41% of patients) than in controls (5% of subjects) (p < 0.01). Lower rectal pain threshold was observed particularly in IBS patients with diarrhea and mixed bowel habits (p < 0.01). Manometric parameters characterizing anal sphincter function are not correlated with the predominant bowel movement pattern in IBS. The features of PFD are significantly more frequent in all subgroups of IBS patients than in controls, suggesting that, in general, IBS patients show changes in the mobility of the pelvic floor. Hypersensitivity to rectal distension is commonly observed in IBS, but it does not seem to be a highly specific marker of the disorder.

Developing Valid and Reliable Health Utilities in Irritable Bowel Syndrome: Results From the IBS PROOF Cohort

A "utility" is a measure of health-related quality of life (HRQOL) that ranges between 0 (death) and 1 (perfect health). Disease-targeted utilities are mandatory to conduct cost-utility analyses. Given the economic and healthcare burden of irritable bowel syndrome (IBS), cost-utility analyses will play an important role in guiding health economic decision-making. To inform future cost-utility analyses in IBS, we measured and validated the IBS utilities. We analyzed data from Rome III IBS patients in the Patient Reported Observed Outcomes and Function (PROOF) Cohort-a longitudinal multi-center IBS registry. At entry, the patients completed a multi-attribute utility instrument (EuroQOL), bowel symptom items, IBS severity measurements (IBS Severity Scale (IBSSS), Functional Bowel Disease Severity Index (FBDSI)), HRQOL indexes (IBS quality-of-life instrument (IBS-QOL), Center for disease control-4 (CDC-4)), and the Worker Productivity Activity Index for IBS (WPAI). We repeated assessments at 3 months. There were 257 patients (79% women; age=43+/-15 years) at baseline and 85 at 3 months. The mean utilities in patients with severe vs. non-severe IBS were 0.70 and 0.80, respectively (P<0.001). There were no differences in utilities among IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and mixed IBS (IBS-M) subgroups. EuroQOL utilities correlated with FBDSI (r=0.31; P<0.01), IBSSS (r=0.36; P<0.01), IBS-QOL (r=0.36; P<0.01), CDC-4 (r=0.44; P<0.01), WPAI presenteeism (r=0.16; P<0.01), abdominal pain (r=0.43; P<0.01), and distension (r=0.18; P=0.01). The utilities in patients reporting "considerable relief" of symptoms at 3 months vs. those without considerable relief were 0.78 and 0.73, respectively (P=0.02). EuroQOL utilities are valid and reliable in IBS. The utility of severe IBS (0.7) is similar to Class III congestive heart failure and rheumatoid arthritis. These validated utilities can be employed in future IBS cost-utility analyses.

W1700 Sub-Groups of Irritable Bowel Syndrome Have a Distinct Colonic Mucosa-Associated Microbiota

W1700 Sub-Groups of Irritable Bowel Syndrome Have a Distinct Colonic Mucosa-Associated Microbiota

Syndrome de l’intestin irritable : aspects évolutifs

Irritable bowel syndrome is a chronic relapsing disorder. In most patients, symptom severity and clinical characteristics change frequently. Nonetheless, broad progressive trends can be defined. Over the very short term, symptoms occur over short sequences appearing sequentially and are interrupted by short remission periods. Over the medium term (3 months), early recovery from symptoms is observed in 20%-40% of patients. No good clinical predictors of IBS progression seem to exist even if clinical improvement at 3 months seems related to a better prognosis after a 1-year follow-up. Over the long term (several years), symptoms are still present in 60%-70% of patients. Symptom turnover is high in these patients from either transitioning into other irritable bowel syndrome subgroups or overlapping with dyspeptic symptoms. Psychiatric comorbidities appear to be of primary importance in the clinical course of patients with irritable bowel syndrome.

An examination of subgroup classification in irritable bowel syndrome patients over time: A prospective study

Background Irritable bowel syndrome (IBS) is a complex functional gastrointestinal disorder which to date remains poorly understood. Therapies for irritable bowel syndrome (IBS) patients are usually aimed at relieving the predominant symptom; however, little evidence exists as to whether or not the predominant symptom changes with time. Nurses are becoming increasingly involved in the assessment and management of IBS patients. Objectives To categorise IBS patients into one of three sub-types, namely diarrhoea-predominant, constipation-predominant and a third group who alternate between the two, and to investigate changes in patient sub-type classification over time. Design Observational cohort study. Setting The general population of the United Kingdom (UK). Methods A cohort of 494 IBS patients, with a confirmed Rome II classification diagnosis, was recruited in the UK. Patients’ IBS symptoms were recorded throughout a 26-week period. Proportions of individuals in each IBS subgroup were calculated and probabilities of moving from one subgroup to another between consecutive weeks were estimated. Results The percentage of patients given an overall subgroup classification of diarrhoea-predominant IBD (D-IBS) is 40.9%; 58.1% and 1% were classified as belonging to the alternator (A-IBS) and constipation-predominant (C-IBS) subgroups, respectively. Patients classified as an alternator or as diarrhoea-predominant have a high probability (0.67 and 0.71, respectively) of remaining in the same subgroup; however this probability is lower for constipation-predominant patients (0.35). Conclusion Although many patients remain in the same IBS subgroup classification over time, there are individuals whose subgroup classification varies. As such, patients’ IBS subgroup classification should be reviewed regularly and treatment adjusted accordingly in order to optimise patient care.

Serotonergic agents and the irritable bowel syndrome: what goes wrong?

It is now nine years since the first large randomised controlled trials showed the benefit of a 5HT(3) antagonist in irritable bowel syndrome (IBS) with diarrhoea (IBS-D) and a 5HT(4) partial agonist in IBS with constipation (IBS-C). Although both of these drugs have now been withdrawn because of rare complications (ischaemic colitis and thrombotic episodes respectively), their clinical effectiveness has stimulated substantial advances in our understanding of the physiological role of serotonin and its disturbance in IBS. 5HT-containing enteroendocrine cells are most numerous in the duodenum and colon and are responsive to a range of stimuli including tastants, mechanic force and short chain fatty acids. Several studies have described an excess of 5HT in IBS-D and abnormally low 5HT availability in IBS-C. Serotonin transporter (SERT) is only weakly expressed in the colon and whether this is further reduced in IBS is unclear with conflicting reports. SERT promoter polymorphisms are inconsistently related to IBS subtypes but appear to partly predict response to both 5HT(3) antagonists and 5HT(4) agonists. Stressors release serotonin and 5HT(3) antagonists have been shown to inhibit the associated acceleration of colonic transit. Newer 5HT(3) antagonists and 5HT(4) agonists are under development. Their undoubted effectiveness in subgroups of IBS should stimulate further work to define biomarkers of both responsiveness and of risk of developing adverse events to improve the risk benefit balance for these potentially useful therapies.

A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome

The purpose of this study was to evaluate the effects of a probiotic combination on symptoms in patients with irritable bowel syndrome (IBS). We investigated the efficiency of a probiotic dietary supplement, containing four strains of lactic acid bacteria, on symptoms of IBS. One hundred and sixteen patients with IBS fulfilling the Rome II criteria were randomized in a parallel group, double-blind study to receive a placebo or a probiotic combination (1 x 10(10) cfu once daily) for four weeks. The symptoms that were monitored weekly included discomfort, abdominal pain, and stool frequency and quality. Quality of life was assessed before and at the end of the treatment using the SF36 and FDD-quality-of-life questionnaires. One hundred subjects completed the study (48 probiotic combination, 52 placebo). The probiotic combination was not superior to the placebo in relieving symptoms of IBS (42.6 versus 42.3% improvement). However, the decrease of abdominal pain between the first and the fourth week of treatment was significantly higher in probiotic treated patients (-41.9 versus -24.2%, P=0.048). Interesting findings from the IBS sub-groups were also observed such as a lower pain score at end point in patients with alternating bowel habits (P=0.023) and an increase of stool frequency in the constipated sub-group from the first week of probiotic treatment (P=0.043). The probiotic combination was not significantly superior to the placebo in relieving symptoms of IBS. Despite the apparent high placebo response, interesting findings from IBS sub-groups were observed in the field of abdominal pain and stool frequency.

Psychological distress and GI symptoms are related to severity of bloating in women with irritable bowel syndrome

Bloating is a frequent complaint of women with irritable bowel syndrome (IBS). We compared retrospective and daily diary gastrointestinal and psychological distress symptoms in 183 women ages 18-48 in three IBS subgroups: Minimal-Bloating, Mild-Bloating, Moderate-Severe-Bloating. More women with moderate to severe levels of bloating reported a history of hard stools, straining to have a stool, a history of depressive disorders, and more severe daily symptoms of depression and anxiety as compared to women with minimal or mild bloating symptoms. Appraising the level of symptom severity and psychological distress is vital to the selection of appropriate treatment options.

Immune Activation in Patients With Irritable Bowel Syndrome

We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines. We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs). PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (1 ng/mL) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6) was measured by enzyme-linked immunosorbent assay. Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale. IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients, whereas constipation-predominant IBS patients showed increased LPS-induced IL-1beta levels compared with HCs. Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than 3 bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .001) with anxiety in patients with IBS. Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.

Lipid-Induced Colonic Hypersensitivity in the Irritable Bowel Syndrome: The Role of Bowel Habit, Sex, and Psychologic Factors

Duodenal lipid infusion increases colonic hypersensitivity in irritable bowel syndrome (IBS). Whether this is affected by bowel habit, psychologic factors, or sex is unknown. We included 61 patients with IBS (50 women, 11 men), 25 with diarrhea-predominant IBS, 17 with constipation-predominant IBS, 19 with alternating-type IBS, and 20 healthy controls (15 women, 5 men). A colonic distension trial was performed with a barostat before and after a 1-hour duodenal lipid infusion (3 kcal/min). Colonic thresholds, colonic tone, and the viscerosomatic referral pattern were assessed and compared between groups. Patients also completed the Hospital Anxiety and Depression scale. The reduction in colonic pressure thresholds after vs before duodenal lipids was greater in patients than in controls for discomfort (P = .006) and pain (P < .0001). An increased viscerosomatic referral area for pain and discomfort during colonic distensions after vs before duodenal lipids was observed in patients but not in controls. The response was similar in IBS subgroups based on the predominant bowel habit, in patients with vs without anxiety and/or depression, and in women and men with IBS. The colonic tone response during lipid infusion was similar in IBS patients and controls, and in the different IBS subgroups. IBS patients show increased colonic sensitivity and altered viscerosomatic referral pattern after duodenal lipids. This response is largely unaffected by the predominant bowel habit, psychologic factors, or sex, but seems to be related to IBS per se.

Neomycin Improves Constipation-Predominant Irritable Bowel Syndrome in a Fashion That Is Dependent on the Presence of Methane Gas: Subanalysis of a Double-Blind Randomized Controlled Study

Recent studies have shown that normalization of the lactulose breath test (LBT) with neomycin leads to a significant reduction in irritable bowel syndrome (IBS) symptoms. This subanalysis was done on the constipation-predominant IBS subgroup of patients (C-IBS) to test the ability of neomycin to improve constipation and its correlation with the elimination of methane on breath test. IBS subjects underwent LBT in a blinded fashion. They were then randomly allocated to neomycin or placebo groups. For the purpose of this analysis, only the C-IBS subjects were identified. They were then evaluated for global improvement, abdominal pain, and constipation severity. The ability of neomycin to eliminate methane and its associated improvement in constipation was also determined. One hundred eleven subjects meeting Rome I criteria for IBS were included in the study. Thirty-nine of these had C-IBS. Of these, 20 received placebo and 19 received neomycin. With neomycin, a global improvement of 36.7+/-7.9% was seen, compared to 5.0+/-3.2% for placebo (P < .001) in the intention-to-treat analysis. Constipation was improved by 32.6+/-9.9% with neomycin compared to 18.7+/-7.2% for placebo (P=.26). Of the original 111 subjects, 12 demonstrated methane on breath test. All 12 of these patients were constipation predominant. In the methane producers receiving neomycin or placebo, improvement in constipation was significantly greater in those receiving neomycin (44.0+/-12.3%) compared to placebo (5.0+/-5.1%) (P < .05). Treatment with neomycin improves constipation in C-IBS. This improvement depends on the presence and elimination of methane on breath test.

Is There an Association Between GNβ3–C825T Genotype and Lower Functional Gastrointestinal Disorders?

GNbeta3 influences G-protein translation of a majority of ligand-receptor activations. It has been reported that functional dyspepsia (FD) is associated with homozygous genotypes of the C825T polymorphism in the GNbeta3 gene. It is unknown whether the GNbeta3 genotype is associated with lower functional gastrointestinal disorders (FGID). We aimed to compare the prevalence of the different GNbeta3-C825T genotypes in patients with lower FGID and healthy controls and to test the associations of these genetic variations with subgroups of irritable bowel syndrome (IBS), functional abdominal pain (FAP), lower FGID-FD overlap, and high somatic symptom scores. GNbeta3-C825T polymorphism was analyzed in DNA from blood samples of 233 patients with lower FGID and 152 healthy controls. A validated bowel questionnaire characterized the FGID phenotype: 82 with IBS constipation, 94 with IBS diarrhea, 38 with IBS alternating bowel function, and 19 with FAP. There were 159 patients with lower FGID and overlap FD using Rome II criteria. Regression analyses assessed associations of the GNbeta3 genotypes with lower FGID as a group, and subgroups of FGID and somatic symptom scores. GNbeta3-C825T genotype distributions were similar between healthy controls (50.7% CC, 40.8% TC) and patients with lower FGID (8.6% TT, 51.5% CC, 40.8% TC, and 7.7% TT). There were no significant associations of GNbeta3-C825T polymorphism with lower FGID overall or with the separate symptom subgroups including IBS, FAP, lower FGID-FD overlap, or high somatic symptom scores. In contrast to the reported association with FD, GNbeta3-C825T polymorphism is not associated significantly with lower FGID, with different IBS or FAP phenotypes, or lower FGID-FD overlap.

Effect of change in an inhibitory neurotransmitter of the myenteric plexus on the pathogenetic mechanism of irritable bowel syndrome subgroups in rat models

In order to investigate the effect of change in an inhibitory neurotransmitter of the myenteric plexus on irritable bowel syndrome (IBS) subgroups, the amounts of nitric oxide (NO) in constipation-predominant (C-IBS) and diarrhea-predominant (D-IBS) IBS models in rats were studied. The D-IBS model was created in rats by intracolonic instillation of acetic acid and by restraint stress. The D-IBS control group underwent intracolonic instillation with saline instead. The C-IBS model was created in rats by gastric instillation of 0-4 degrees C cool water daily for 14 days. The C-IBS control group underwent gastric instillation with saline instead. A blank control group was also made. Viscerosomatic sensitivity was assessed with electromyographic (EMG). Abdominal contractions induced by distension of a colonically inserted balloon (0-1.6 mL) was recorded in rats by implanting electrodes in the abdominal external oblique muscle. An India ink gastric instillation experiment was used to detect the bowel movement and fecal pellets formation. Histological analysis of colonic tissue was performed. Nicotinamide dinucleotide phosphate (NADPH)-diaphorase staining was used to detect positive NO neurons in the myenteric plexus. When the balloon was distended by high volume, there were significantly more contractions of abdominal muscle in D-IBS compared with C-IBS and the control groups (P < 0.05). When the balloon was distended by low volume, there were significantly fewer contractions of abdominal muscle in C-IBS compared with D-IBS and the control groups (P < 0.05). The wet weight and water content of the feces expelled by the rats in the C-IBS and the C-IBS control groups were significantly lower than those in the blank control group (P < 0.05). The time before the first black stool in the C-IBS group was significantly longer than that in the blank control group and C-IBS control group (P < 0.05). Histological analysis of the colon showed no colonic inflammation in any group. The number of NO-positive neurons in the C-IBS group was significantly greater than in the D-IBS and control groups (P < 0.01), although there was no significant difference in the number of neurons between the D-IBS and the control groups (P > 0.05). Enhanced inhibitory neurotransmitter NO in the myenteric plexus of the colon is related to IBS subgroups, visceral sensitivity and motility dysfunction. The results reveal that NO plays a role in the pathogenetic mechanism of IBS subgroups.

Hypothalamic-Pituitary-Gut Axis Dysregulation in Irritable Bowel Syndrome: Plasma Cytokines as a Potential Biomarker?

Irritable bowel syndrome (IBS) is a functional disorder with an etiology that has been linked to both psychological stress and infection. The primary aim of this study was to examine the hypothalamic-pituitary-adrenal axis in patients with IBS and to relate such response to plasma cytokine profiles. A total of 151 subjects, 76 patients and 75 controls, were recruited. The patients with IBS were diagnosed according to Rome II criteria. Forty-nine patients and 48 matched controls had cytokine levels measured, and a subset of 21 patients and 21 controls also underwent a corticotropin-releasing hormone (CRH) stimulation test with plasma levels of adrenocorticotropic hormone (ACTH) and cortisol measured. The remaining 27 patients and 27 controls underwent a dexamethasone (1 mg) challenge. Cortisol and the proinflammatory cytokines interleukin (IL)-6 (together with its soluble receptor) and IL-8 were elevated in all IBS subgroups (diarrhea predominant, constipated, and alternators), although the elevation was most marked in the constipated subgroup. There was no alteration in the anti-inflammatory cytokine IL-10. Following CRH infusion, an exaggerated release of both ACTH and cortisol was observed in patients with IBS. There was a significant correlation between the ACTH response (deltaACTH) and the IL-6 levels. A similar relationship existed between the deltaACTH/deltacortisol ratio and the IL-6 levels. Dexamethasone suppression of cortisol was similar in patients and controls. IBS is characterized by an overactivation of the hypothalamic-pituitary-adrenal axis and a proinflammatory cytokine increase.

A symptom-based approach to making a positive diagnosis of irritable bowel syndrome with constipation

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Characterised by abdominal pain or discomfort, bloating and altered bowel habit, IBS is a chronic recurring condition, typically affecting up to 15% of the Western population, IBS can be subclassified into IBS with constipation (IBS-C), IBS with diarrhoea (IBS-D), or IBS with alternating constipation or diarrhoea symptoms (IBS-A). Conventional clinical diagnosis focuses on excluding all potential organic causes of patient symptoms. However, a positive diagnosis of IBS may be established using published criteria such as the Manning and/or Rome criteria. While these methods are useful to identify patients with IBS who are suitable for enrollment into clinical trials, the criteria are relatively complex and not readily applicable to general practice. In this review we present an 'identify, eliminate, probe' algorithm that may be appropriate to establish a positive diagnosis of patients with IBS-C, as symptoms characteristic of patients in this IBS subgroup are least likely to be confused with symptoms reflecting serious organic disease.

New Criteria for Irritable Bowel Syndrome Based on Prospective Symptom Evaluation

In a population prevalence questionnaire study we demonstrated that constipation and fecal incontinence are common problems in the general Swedish population with a similar magnitude as in other Western countries. 95.6% of the population had between three bowel movements per day and three per week. Constipation was mostly defined by “hard stools” and “the need of using laxatives”. Irritable Bowel Syndrome (IBS) is characterized by abdominal pain/discomfort and abnormal bowel habits. The diagnostic criteria of IBS are based on clinical symptoms. Division of IBS patients into symptom subgroups appears important as their bowel symptoms are characterized by heterogeneity. International criteria to subgroup IBS (Rome II) are based on expert consensus and not on evidence. We investigated the variation of stool consistency and defecatory symptoms in 135 IBS patients by symptom diary cards. Most patients had alternating stool consistency. When subgroups were based on stool consistency, all kinds of defecatory symptoms (straining, urgency, and feeling of incomplete evacuations) were frequently present in all subgroups. Stool frequency was in the normal range in the majority of patients. We propose that IBS subgroups should be based on stool consistency. We suggest that Rome II supportive criteria must be reconsidered as the determination of presence or absence of specific symptoms does not work as an instrument for categorization of IBS patients into diarrhoea- and constipation-predominant. We also propose that abnormal stool frequency should be excluded to define subgroups of IBS. Alternating stool consistency and presence of different defecatory symptoms, regardless of stool consistency should be included as criteria for IBS. Stress is known to play an important role in the onset and modulation of IBS symptoms. From experimental studies there is evidence for a stress-dependent alteration of visceral sensitivity. The biological mechanisms responsible for the causal link between stress and IBS symptoms are not completely understood, but the hypothalamic-pituitary-adrenocortical axis and the autonomous nervous system seem to play a prominent role in the pathophysiology of IBS. We investigated visceral sensitivity and the effect of repeated maximal tolerable rectal distensions on salivary cortisol levels and skin conductance in patients with IBS, chronic constipation and healthy volunteers. We found that the expectancy of the experimental situation per se (provocation of bowel symptoms by rectal distensions) compared to non-experimental days at home measured as salivary cortisol had a high impact on the level of arousal in IBS. IBS patients had higher skin conductance values than controls in the beginning of distension series and lower rectal thresholds for first sensation, urge and discomfort than healthy controls and constipation patients. IBS patients demonstrated habituation to repeated subjective maximal tolerable rectal distensions according to sympathetic activity although patients continued to rate their discomfort as maximal. Constipation patients had lower sympathetic activity than IBS patients before and during repeated rectal distensions. None of the groups demonstrated a significant increase in cortisol after repetitive rectal distensions. We conclude that Rome II supportive criteria for IBS should be reconsidered according to our findings. IBS patients are more sensitive to pre-experimental stress than healthy controls and patients with constipation. This should be considered in the design of experimental IBS studies. IBS patients habituated to subjective maximal tolerable, repetitive rectal distensions with decreasing sympathetic activity. Since responses to repeated stimuli of close-to-pain intensities are resistant to habituation this finding could be caused by psychological influences on perception, that is, perceptual response bias.

Role of Tumor Necrosis Factor-alpha and Interleukin-10 Gene Polymorphisms in Irritable Bowel Syndrome

Imbalances in the genetically controlled pro- and anti-inflammatory cytokine production may promote ongoing low-grade inflammation after an acute gastroenteritis, and subsequently, irritable bowel syndrome (IBS) (post-infectious IBS, PI-IBS). We studied gene promoter single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNF-alpha, pro-inflammatory) and interleukin-10 (IL-10, anti-inflammatory) in IBS patients and controls. DNA was extracted from peripheral blood leucocytes of 111 IBS patients and 162 healthy controls. Genotype and allele frequencies were assessed by analyzing SNPs at position -308 (TNF-alpha) and -1082 and -819 (IL-10). Homozygous high producers for TNF-alpha (A/A) were rare (overall prevalence 2.6%). The heterozygous TNF-alpha genotype (G/A, high producer) was significantly more prevalent in IBS compared to controls (41%vs 26%, p= 0.02). More patients (41%) than controls (30%) were positive for the A allele (p= 0.044; odds ratio (OR) 1.68, 95% confidence interval (CI) 1.01-2.79), with a similar trend for diarrhea (54%) versus constipation and alternating subtypes (<33%, p= 0.079), but not for subgroups according to a history of acute gastroenteritis. IL-10 genotypes were similarly distributed in patients and controls for both SNPs. Possession of a high producer TNF-alpha and a low producer IL-10 genotype were significantly more prevalent in IBS (9%) versus controls (3%, p= 0.035; OR 3.11, 95% CI 1.03-9.36) and in diarrhea (20%) compared to other IBS subtypes (<4%, p= 0.026). Our results support the emerging hypothesis that genetically determined immune activity plays a role in the pathophysiology of IBS. Future studies in larger, clinically relevant, IBS subgroups are warranted to establish definite associations with cytokine gene polymorphisms.