A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is subtyped as IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C) based on Rome II guidelines. The remaining group is considered as having mixed IBS (IBS-M). There is no standard definition of an alternator (IBS-A), in which bowel habit changes over time. Our aim was to use Rome II criteria to prospectively assess change in bowel habit for more than 1 year to understand IBS-A. METHODS: Female patients (n=317) with IBS entering a National Institutes of Health treatment trial were studied at baseline with questionnaires and 2-week daily diary cards of pain and stool frequency and consistency. Studies were repeated at the end of treatment (3 months) and at four 3-month intervals for one more year. Algorithms to classify subjects into IBS-D, IBS-C, and IBS-M groups used diary card information and modified Rome II definitions. Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures. RESULTS: At baseline, 36% had IBS-D, 31% IBS-M, and 34% IBS-C. Except for stool frequency, there were no differences between groups. While the proportion of subjects in each subgroup remained the same over the year, most individuals (more than 75%) changed to either of the other 2 subtypes at least once. IBS-M was the least stable (50% changed out by 12 weeks). Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably, only 29% switched between the IBS-D and IBS-C subtypes over the year. CONCLUSIONS: While the proportion of subjects in each of the IBS subtypes stays the same, individuals commonly transition between subtypes, particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period.     

Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome

AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome (IBS).METHODS: Seventy-six patients with IBS were included in the study (62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome III criteria for functional dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29 had constipation as the predominant symptom (IBS-C). Forty-three age and sex-matched healthy volunteers without any gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex (ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software (version 1.7).RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and 126 (0, 262) cells/mm², respectively. There was a significant difference between the tested groups (P < 0.0001). Dunn’s multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489 (130, 966), and in those with IBS only 490 (130, 956). There was no statistical significant difference between these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density (r = 0.65; P < 0.0001) and significantly inversely correlated with that of constipation (r = 90.69; P < 0.0001). The densities of the serotonin cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups (P < 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65 (25, 123). There was no statistically significant difference between these 2 groups of patients (P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups (P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire (r = 0.56; P < 0.0001) and significantly inversely correlated with that of constipation (r = 0.51; P < 0.0001). The densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80), 46 (0, 103) and 206 (194, 314) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically significant difference between the controls and the IBS subgroups (P < 0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls (P < 0.01, P = 0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no statistically significant difference between these 2 groups of patients (P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density (r = 0.38; P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P < 0.0001).CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility.     

Endocrine cells in the ileum of patients with irritable bowel syndrome

AIM: To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients.METHODS: Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software.RESULTS: The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm² in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm² in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm² in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm² in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells.CONCLUSION: The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.     

Reduction in duodenal endocrine cells in irritable bowel syndrome is associated with stem cell abnormalities

AIM: To determine whether the decreased density of duodenal endocrine cells in irritable bowel syndrome (IBS) is associated with abnormalities in stem cell differentiation.METHODS: The study sample comprised 203 patients with IBS (180 females and 23 males with a mean age of 36 years) and a control group of 86 healthy subjects without gastrointestinal complaints (77 females and 9 males with a mean age of 38 years). The patients included 80 with mostly diarrhoea (IBS-D), 47 with both diarrhoea and constipation (IBS-M), and 76 with mostly constipation (IBS-C). Both the patients and controls underwent gastroscopy and four biopsy samples were taken from the descending part of the duodenum, proximal to the papilla of Vater. The biopsy samples were sectioned and immunostained for Musashi 1 (Msi-1), neurogenin 3 (NEUROG3), secretin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), somatostatin and serotonin. Immunostaining was performed with an ultraView Universal DAB Detection Kit (v1.02.0018, Venata Medical Systems, Basal, Switzerland) using the BenchMark Ultra immunohistochemistry/in situ hybridization staining module (Venata Medical Systems). Endocrine cell densities were quantified by computerized image analysis using the Olympus cellSens imaging program.RESULTS: The densities of Msi-1 and NEUROG3 cells were significantly lower in IBS patients, regardless of the subtype, than in the controls (77 ± 17 vs 8 ± 2; P = 0.0001, and 351 ± 33 vs 103 ± 22; P = 0.00002, respectively). Furthermore, the densities of secretin, and CCK cells were significantly lower in patients with diarrhoea as the predominant IBS symptom (IBS-D) than in the controls (161 ± 11 vs 88 ± 8; P = 0.00007, and 325 ± 41 vs 118 ± 10; P = 0.00006, respectively), but not in patients with constipation as the predominant IBS symptom (IBS-C) or those with both diarrhoea and constipation (IBS-M). The GIP cell density was significantly reduced in both IBS-D (152 ± 12 vs 82 ± 7; P = 0.00003), and IBS-C (152 ± 12 vs 107 ± 8; P = 0.01), but not in IBS-M. The densities of somatostatin cells in the controls and the IBS-total, IBS-D, IBS-M and IBS-C patients were 81 ± 8, 28 ± 3, 20 ± 4, 37 ± 5 and 28 ± 4 cells/mm² epithelium, respectively. The density of somatostatin cells was lower in IBS-total, IBS-D, IBS-M and IBS-C patients than in the controls (P = 0.00009, 0.00006, 0.009 and 0.00008, respectively). The density of serotonin cells did not differ between IBS patients and controls.CONCLUSION: The reduction in duodenal endocrine cells in IBS patients found in this study is probably attributable to the reduction in cells expressing Msi-1 and NEUROG3.     

Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation

AIM: To determine effect of irritable bowel syndrome(IBS) subtype on IBS-specific quality of life(QOL) questionnaire and its subscales.METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States.IBS and IBS subtype were diagnosed using Rome-Ⅲ questionnaire.QOL was assessed using IBS-QOL questionnaire.IBSQOL assesses quality of life along eight subscales: dysphoria,interference with activities,body image,health worry,food avoidance,social reactions,sexual health,and effect on relationships.IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL.Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI.We compared mean IBS-QOL score and its subscales among various IBSsubtypes.Analysis of variance(ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender.A posthoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05.RESULTS: Of 542 patients screened,243 had IBS as per Rome-Ⅲ criteria.IBS-mixed(IBS-M) was the most common IBS subtype(121 patients,49.8%) followed by IBS- diarrhea(IBS-D)(56 patients,23.1%),IBSconstipation(IBS-C)(54 patients,22.2%) and IBSunspecified(IBS-U)(12 patients,4.9%).Overall IBSQOL scores were significantly different among various IBS-subtypes(P = 0.01).IBS-QOL of patients with IBS-D(61.6,95%CI: 54.0-69.1) and IBS-M(63.0,95%CI: 58.1-68.0) was significantly lower than patients with IBS-C(74.5,95%CI: 66.9-82.1)(P = 0.03 and 0.02 respectively).IBS-D patients scored significantly lower than IBS-C on food avoidance(45.0,95%CI: 34.8-55.2 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and interference with activity(59.6,95%CI: 51.4-67.7 vs 82.3,95%CI: 74.1-90.6,P 0.001).IBS-M patients had more interference in their activities(61.6,95%CI: 56.3-66.9 vs 82.3,95%CI: 74.1-90.6,P = 0.001) and greater impact on their relationships(73.3,95%CI: 68.4-78.2 vs 84.7,95%CI: 77.2-92.2,P = 0.02) than IBS-C patients.Patients with IBS-M also scored significantly lower than IBS-C on food avoidance(47.2,95%CI: 40.7-53.7 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and social reaction(66.1,95%CI: 61.1-71.1 vs 80.0,95%CI: 72.1-87.7,P = 0.005).CONCLUSION: IBS-D and IBS-M patients have lower IBS-QOL than IBS-C patients.Clinicians should recognize food avoidance,effects on daily activities and relationship problems in these patients.     

Irritable bowel syndrome: Pathogenesis,diagnosis, treatment,and evidence-based medicine

Irritable bowel syndrome(IBS)is a chronic and debilitating functional gastrointestinal disorder that affects9%-23%of the population across the world.The percentage of patients seeking health care related to IBS approaches 12%in primary care practices and is by far the largest subgroup seen in gastroenterology clinics.It has been well documented that these patients exhibit a poorer quality of life and utilize the health care system to a greater degree than patients without this diagnosis.The pathophysiology of IBS is not clear.Many theories have been put forward,but the exact cause of IBS is still uncertain.According to the updated ROMEⅢcriteria,IBS is a clinical diagnosis and presents as one of the three predominant subtypes:(1)IBS with constipation(IBS-C);(2)IBS with diarrhea(IBS-D);and(3)mixed IBS(IBS-M);former ROME definitions refer to IBS-M as alternating IBS(IBS-A).Across the IBS subtypes,the presentation of symptoms may vary among patients and change over time.Patients report the most distressing symptoms to be abdominal pain,straining,myalgias,urgency,bloating and feelings of serious illness.The complexity and diversity of IBS presentation makes treatment difficult.Although there are reviews and guidelines for treating IBS,they focus on the efficacy of medications for IBS symptoms usinghigh-priority endpoints,leaving those of lower priority largely unreported.Therefore,the aim of this review is to provide a comprehensive evidence-based review of the diagnosis,pathogenesis and treatment to guide clinicians diagnosing and treating their patients.     

Pharmacologic and complementary and alternative medicine therapies for irritable bowel syndrome

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by episodic abdominal pain or discomfort in association with altered bowel habits (diarrhea and/or constipation). Other gastrointestinal symptoms, such as bloating and flatulence, are also common. A variety of factors are believed to play a role in the development of IBS symptoms, including altered bowel motility, visceral hypersensitivity, psychosocial stressors, altered brain-gut interactions, immune activation/low grade inflammation, alterations in the gut microbiome, and genetic factors. In the absence of biomarkers that can distinguish between IBS subgroups on the basis of pathophysiology, treatment of this condition is predicated upon a patient's most bothersome symptoms. In clinical trials, effective therapies have only offered a therapeutic gain over placebos of 7-15%. Evidence based therapies for the global symptoms of constipation predominant IBS (IBS-C) include lubiprostone and tegaserod; evidence based therapies for the global symptoms of diarrhea predominant IBS (IBS-D) include the probiotic Bifidobacter infantis, the nonabsorbable antibiotic rifaximin, and alosetron. Additionally, there is persuasive evidence to suggest that selected antispasmodics and antidepressants are of benefit for the treatment of abdominal pain in IBS patients. Finally, several emerging therapies with novel mechanisms of action are in development. Complementary and alternative medicine therapies including probiotics, herbal therapies and acupuncture are gaining popularity among IBS sufferers, although concerns regarding manufacturing standards and the paucity of high quality efficacy and safety data remain.     

Diarrhoea-predominant irritable bowel syndrome distinguishable by 16S rRNA gene phylotype quantification

AIM: To study whether selected bacterial 16S ribosomal RNA (rRNA) gene phylotypes are capable of distinguishing irritable bowel syndrome (IBS).METHODS: The faecal microbiota of twenty volunteers with IBS, subdivided into eight diarrhoea-predominant (IBS-D), eight constipation-predominant (IBS-C) and four mixed symptom-subtype (IBS-M) IBS patients, and fifteen control subjects, were analysed at three timepoints with a set of fourteen quantitative real-time polymerase chain reaction assays. All assays targeted 16S rRNA gene phylotypes putatively associated with IBS, based on 16S rRNA gene library sequence analysis. The target phylotypes were affiliated with Actinobacteria, Bacteroidetes and Firmicutes. Eight of the target phylotypes had less than 95% similarity to cultured bacterial species according to their 16S rRNA gene sequence. The data analyses were made with repeatedmeasures ANCOVA-type modelling of the data and principle omponent analysis (PCA) with linear mixed-effects models applied to the principal component scores. RESULTS: Bacterial phylotypes Clostridium cocleatum 88%, Clostridium thermosuccinogenes 85%, Coprobacillus catenaformis 91%, Ruminococcus bromii-like, Ruminococcus torques 91%, and R. torques 93% were detected from all samples analysed. A multivariate analysis of the relative quantities of all 14 bacterial 16S rRNA gene phylotypes suggested that the intestinal microbiota of the IBS-D patients differed from other sample groups. The PCA on the first principal component (PC1), explaining 30.36% of the observed variation in the IBS-D patient group, was significantly altered from all other sample groups (IBS-D vs control, P = 0.01; IBS-D vs IBS-M, P = 0.00; IBS-D vs IBS-C, P = 0.05). Significant differences were also observed in the levels of distinct phylotypes using relative values in proportion to the total amount of bacteria. A phylotype with 85% similarity to C. thermosuccinogenes was quantified in significantly different quantities among the IBS-D and control subjects (-4.08 ± 0.90 vs -3.33 ± 1.16, P = 0.04) and IBS-D and IBS-M subjects (-4.08 ± 0.90 vs -3.08 ± 1.38, P = 0.05). Furthermore, a phylotype with 94% similarity to R. torques was more prevalent in IBS-D patients' intestinal microbiota than in that of control subjects (-2.43 ± 1.49 vs -4.02 ± 1.63, P = 0.01). A phylotype with 93% similarity to R. torques was associated with control samples when compared with IBS-M (-2.41 ± 0.53 vs -2.92 ± 0.56, P = 0.00). Additionally, a R. bromii-like phylotype was associated with IBS-C patients in comparison to control subjects (-1.61 ± 1.83 vs -3.69 ± 2.42, P = 0.01). All of the above mentioned phylotype specific alterations were independent of the effect of time.CONCLUSION: Significant phylotype level alterations in the intestinal microbiotas of IBS patients were observed, further emphasizing the possible contribution of the gastrointestinal microbiota in IBS.     

Abnormal Propagation Pattern of Duodenal Pressure Waves in the Irritable Bowel Syndrome (IBS)

The propagation pattern of individual pressure waves in the gastroduodenal area in IBS is unexplored. We performed antroduodenojejunal manometry on 26 patients with IBS—13 with diarrhea predominant IBS (IBS-D) and 13 with constipation predominant IBS (IBS-C)—and 32 healthy controls. Neuropathic-like motor abnormalities were found in 38% of the patients with conventional manometric evaluation. With high-resolution analysis additional abnormalities were observed in the majority of the patients, with increased frequency of retrograde pressure waves postprandially in both IBS subgroups and in phase II in IBS-D. A correlation between subjective gastrointestinal symptoms and the frequency of retrograde pressure waves in phase II in IBS-D was demonstrated. Motility indices and the number of long clusters were also higher in patients compared to controls. To conclude, an abnormal propagation pattern of individual duodenal pressure waves in IBS patients was demonstrated and found to be related to symptom severity in diarrhea-predominant IBS. High-resolution analysis adds information to standard manometry.     

Sex differences in irritable bowel syndrome in Japanese university students

Background Epidemiological studies of irritable bowel syndrome (IBS) among young adults are few, especially in Asian countries. Our aim was to examine the prevalence of IBS, whether there was a sex difference, and whether allergic diseases were important risk factors for IBS in young adults. Methods Newly enrolled university students completed health survey questionnaires regarding general health. Those with gastrointestinal symptoms completed the Gastrointestinal Symptom Rating Scale (GSRS) and an additional questionnaire covering the presence of allergic manifestations. IBS was diagnosed based on the Rome II criteria. Results IBS was diagnosed in 268 of 2495 students [10.7%; constipation-predominant type (IBS-C), 128; diarrhea-predominant type (IBS-D), 117; unclassified, 23]. IBS-C was associated with female sex (odds ratio, 6.4; 95% confidence interval, 4.1–9.7; P < 0.001), whereas there was no sex difference in IBS-D. The proportions of subjects with food sensitivity were significantly different among the three groups (4.0%, subjects without IBS; 8.6%, IBS-C group; and 15.4%, IBS-D group) (P < 0.001). The median GSRS scores for pain (1.67 vs 1, P = 0.001), indigestion (1.75 vs 1.5, P < 0.001), and constipation (2.0 vs 1.33, P < 0.001) were higher, and the median diarrhea score was lower (1.33 vs 1.67) (P < 0.001), in women than in men. The median score for diarrhea (2.33 vs 1.67, P = 0.001) was significantly higher in subjects with food sensitivity than in those without. Conclusions There was a strong relationship between IBS-C and female sex, and food sensitivity seemed to be an exacerbating factor for IBS-D. There is no conflict of interest.     

Irritable bowel syndrome consulters in Zhejiang province： The symptoms pattern, predominant bowel habit subgroups and quality of life

AIM: To investigate the pattern of symptoms, predominant bowel habits and quality of life (QOL) by the Chinese version of the SF-36 in irritable bowel syndrome (IBS) consulters in Zhejiang province. METHODS: From January 2001 to January 2002, 662 Roma Ⅱ criteria-positive IBS patients were enrolled by gastroenterologists in 10 hospitals from Digestive Disease Center of Zhejiang (DDCZ). Patients were classified into constipation predominant IBS (IBS-C), diarrhea predominant IBS (IBS-D) and alternating constipation and diarrhea IBS (IBS-A) according to the predominant bowel habits. All patients were evaluated for the demographic checklists, IBS bowel symptoms, extra-colonic symptoms, and QOL by Chinese version of the SF-36 questionnaire. RESULTS: (1) Besides abdominal pain, the predominant colonic symptoms were in order of altered stool form, abnormalities of stool passage, abdominal distension and passage of mucus in IBS patients. Also, IBS subjects reported generalized body discomfort and psychosocial problems including dyspeptic symptoms, poor appetite, heartburn, headache, back pain, difficulty with urination, fatigue, anxiety and depression. (2) IBS-C and IBS-A are more common among female patients, whereas male patients experienced more cases of IBS-D. In regards to the IBS symptoms, there were significant differences among IBS subgroups. Abdominal pain (frequency ≥2 days per week and duration ≥1 hour per day) was frequent in IBS-A patients (P=0.010 and 0.027, respectively), IBS-D patients more frequently experienced the passage of mucus, dyspeptic symptoms and anxiety (P=0.000, 0.014 and 0.015, respectively). (3) IBS patients experienced significant impairment in QOL, decrements in QOL were most pronounced in vitality, general health, mental health, and bodily pain. Compared with the general population (adjusted for gender and age), IBS patients scored significantly lower on all SF-scales (P&lt;0.001), except for physical function scale (P=0.149). (4) QOL was impaired in all subgroups, particularly in scales of vitality, general health and mental health. Compared with IBS-D, QOL in IBS-C scored significantly lower on physical function, role physical, general health, role emotional, and mental health scales (P=-0.037, 0.040, 0.039, 0.005 and 0.026, respectively). CONCLUSION: Besides colonic symptoms, IBS could cause generalized body discomfort and psychosocial problems. The IBS subgroups based on predominant bowel habits are helpful to identify clinical distinction of the IBS. QOL is significantly impaired in IBS patients. The Chinese version of the SF-36 health survey scales may be a useful measurement of IBS patients.     

Impact of upper digestive symptoms in patients with irritable bowel syndrome

BACKGROUND: Functional digestive disorders constitute a sizable proportion of gastroenterology and primary healthcare consultations, and have a negative impact on health-related quality of life. Dyspepsia and heartburn are often associated with irritable bowel syndrome (IBS); however, the incidence of these symptoms and their effect on IBS patients have not been evaluated. AIM: To investigate the clinical, psychological and health-related quality of life impact of upper digestive symptoms on IBS patients. METHODS: A prospective, observational, multicentered study was conducted in Spain: 517 IBS patients (Rome II criteria), grouped according to predominant symptoms of constipation (IBS-C), diarrhea (IBS-D) or alternating bowel habit (IBS-A) and 84 controls without IBS were recruited. Upper digestive symptoms were recorded in a 30-day diary. Health-related quality of life was evaluated by Irritable Bowel Syndrome Quality of Life and Euro-Quality of Life Five-Dimension Questionnaires; psychological well-being was evaluated by the Psychological General Well-Being Index. RESULTS: IBS patients had greater frequencies of upper digestive symptoms (72.3 vs. 6.0%), dyspepsia (21.1 vs. 4.8%) and heartburn (40.0 vs. 13.1%) (all P < 0.05) than controls. Prevalence of upper digestive symptoms was lower in patients with IBS-D than in those with IBS-C or IBS-A (P < 0.05). Health-related quality of life and psychological status were significantly worse in IBS patients with upper digestive symptoms than in those without. CONCLUSIONS: Upper digestive symptoms, frequently present in IBS patients, impair health-related quality of life and psychological status. This effect is greater in patients with IBS-C and IBS-A than in those with IBS-D. These data emphasize the importance of evaluating the presence of upper digestive symptoms in IBS patients.     

Quality of Life in Patients with Irritable Bowel Syndrome Seen in Referral Centers Versus Primary Care: The Impact of Gender and Predominant Bowel Pattern

Background: Quality of life (QOL) is reduced in patients with irritable bowel syndrome (IBS) and little is known about differences in QOL in relation to referral status, gender and predominant bowel pattern in IBS patients. This study aimed to explore these relationships. Methods: 343 patients with IBS according to the Rome I criteria (251 females, 92 males) completed five different self-administered questionnaires to evaluate QOL. There were 119 patients with diarrhea-predominant IBS (IBS-D), 93 with constipationpredominant IBS (IBS-C) and 131 with alternating constipation and diarrhea (IBS-A). The study group comprised 209 hospital outpatients and 134 primary care patients. The questionnaires were mailed to the patients with an overall response rate of 88%. Results: QOL was reduced in hospital outpatients compared to primary care patients, but only in females. IBS subgroup (IBS-D), physical fatigue and general health independently predicted referral to a gastroenterologist. Females had lower QOL than males. No differences, except in severity of diarrhea and constipation, were observed between IBS subgroups. Perceived fatigue was related to well-being, psychological and gastrointestinal symptoms. Independent predictors for fatigue were depression, trait anxiety, general health and vitality, along with eating dysfunction and female sex. Conclusion: IBS female patients seen in referral centers versus primary care is a highly selected group with reduced QOL. QOL in IBS is affected by gender, but not by subgroup. Our findings have implications for the generalizability of results in IBS trials. Fatigue is a common symptom in IBS that correlates to general well-being and psychological and subjective gastrointestinal symptoms.     

Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea

OBJECTIVES: Distinguishing between irritable bowel syndrome (IBS) and functional dyspepsia can be challenging because of the variations in symptom patterns, which commonly overlap. However, the overlap is poorly quantified, and it is equally uncertain whether symptom patterns differ in subgroups of IBS arbitrarily defined by primary bowel patterns of constipation (IBS-C) and diarrhea (IBS-D). We aimed to determine and to compare the distribution of GI symptoms, both, upper and lower, among IBS-C and IBS-D patients. METHODS: A total of 121 consecutive patients presenting with a diagnosis of IBS were grouped according to primary bowel symptoms as IBS-C (58 women and 18 men, mean age 47 +/- 17 yr) or IBS-D (26 women and 19 men, mean age 47 +/- 15 yr). The Hopkins Bowel Symptom Questionnaire, which includes a brief Quality of Life assessment, and the Hopkins Symptom Checklist 90-Revised were completed by all patients at intake. RESULTS: IBS-C patients reported significantly more overall GI symptoms when compared to patients with IBS-D (6.67 vs 4.62, respectively, p<0.001). Abdominal pain patterns differed in patients with IBS-C versus IBS-D (lower abdominal pain: 40.8% vs 24.4% p=0.05 and upper abdominal pain: 36.8% vs 24.4%, respectively). Bloating was substantially more common in IBS-C patients (75%) than in IBS-D (40.9%). There were no significant differences in personality subscales by IBS subgroup; however, somatization was positively associated with multiple symptom reports and was negatively correlated with quality of life. CONCLUSIONS: Upper GI symptoms consistent with functional dyspepsia were more frequent in IBS-C. Although there was considerable overlap of upper and lower GI symptoms in patients with IBS-C and IBS-D, the former had more frequent lower abdominal pain and bloating.     

Tegaserod for female patients suffering from IBS with mixed bowel habits or constipation: a randomized controlled trial

OBJECTIVES: Though the greatest proportion of irritable bowel syndrome (IBS) patients report a mixed bowel pattern (IBS-Mixed), no available therapies have been rigorously evaluated in this subgroup. This study aimed to evaluate the efficacy and safety of the 5-HT₄ agonist tegaserod in women with IBS-Mixed and IBS with constipation (IBS-C).
METHODS: This prospective, double-blind, randomized, placebo-controlled, multicenter study was conducted in 100 centers in North America, South America, and Europe. Women with IBS-Mixed or IBS-C received tegaserod 6 mg or placebo twice daily. The primary efficacy variable was the patient's assessment of satisfactory relief over the 4-wk treatment period. The proportion of patients reporting satisfactory relief for ≥3 of 4 treatment weeks (75% rule) and individual IBS symptoms were assessed.
RESULTS: In total, 661 women were randomized (IBS-Mixed 324, IBS-C 337). Baseline symptom assessments identified clear differences between the two cohorts. Tegaserod provided significant improvement in satisfactory relief of IBS symptoms over 4 wk (OR 1.75, 95% CI 1.35–2.25, P < 0.001) in both IBS-Mixed and IBS-C patients. Using the 75% rule, 52.3% of tegaserod-receiving IBS-M patients and 43.3% of IBS-C patients were responders ( vs 36.3, OR 1.88, 95% CI 1.16–3.04, P < 0.010; and 28.9, OR 1.90, 95% CI 1.19–3.05, P < 0.008 for placebo, respectively). The most frequent adverse events leading to study discontinuation in tegaserod-treated patients were diarrhea (1.5%) and abdominal pain (0.9%). Overall 7% of IBS-C patients reported diarrhea compared to 12% of IBS-Mixed (placebo 2.4%, 1.8%, respectively).
CONCLUSIONS: Tegaserod is effective in treating overall IBS symptoms in patients with IBS-Mixed and IBS-C.     

Novel pharmacological therapies for irritable bowel syndrome

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder, which represents a major cost to healthcare services. Current pharmacological treatment includes fibre supplements, antispasmodics, laxatives, loperamide and antidepressants. This article reviews the novel pharmacological treatments already or recently approved for patients with IBS-C (lubiprostone, linaclotide) and IBS-D (alosetron, ramosetron, rifaximin, eluxadoline). Furthermore, results for drugs in development (plecanatide, ibudutant and ebastine) or used in chronic constipation or for other indications, with potential application in IBS (prucalopride, elobixibat, mesalazine, ondansetron and colesevelam) are also reviewed.     

Treatment of irritable bowel syndrome with a novel colonic irrigation system: a pilot study

Background

Medical treatments for irritable bowel syndrome (IBS) are often disappointing. A colonic irrigation system, the Ashong colonic irrigation apparatus (ACIA), was designed as a patient-administered device for defecation disorders. This pilot study evaluated the efficacy and safety of ACIA for IBS.

Methods

Eighteen patients, 12 with constipation-dominant IBS (IBS-C) and 6 with diarrhea-dominant IBS (IBS-D) group, were studied. Patients were randomized into treatments of 1–4 weeks. Colonic irrigation was performed twice daily for 6 consecutive days per week. To determine the response to treatment, bowel movement frequency, stool consistency, abdominal pain, patient satisfaction with bowel movements, and distress/discomfort due to symptoms were assessed.

Results

The scores of abdominal pain (p < 0.001), satisfaction (p < 0.001), and distress/discomfort (p < 0.001) improved significantly. The frequency of bowel movements in the IBS-C group increased from 1.68 to 3.78 times per week (p < 0.001). The occurrence of Bristol Stool Scale type 1 and 2 stool passage decreased from 45 to 13 % (p = 0.009) in the IBS-C group and type 6 and 7 stools decreased from 62 to 28 % (p = 0.005) in the IBS-D group. Only mild adverse events occurred, and all patients completed treatment.

Conclusions

Colonic irrigation with ACIA is safe and can improve abdominal pain, constipation, and diarrhea associated with IBS. Patients were more satisfied with their bowel movements and found their symptoms were less disturbing. Larger studies on long-term efficacy and quality of life and on placebo effects are needed.

     

Prevalence of microscopic colitis in patients with irritable bowel syndrome with diarrhea predominance

Background: Microscopic colitis (MC) and irritable bowel syndrome with diarrhea (IBSD) have a similar clinical and endoscopic presentation. The prevalence of MC in Mexican patients with IBS-D is unknown. Objectives: To find out the prevalence of MC in patients with IBS-D and compare it with the one observed in patients with IBS with constipation (IBS-C). Methods: All patients with IBS (Rome III) seen consecutively from January 2008 to August 2010 were included. Those with organic disease, alarm signs, mixed IBS or unsubtyped- IBS (Rome III) were excluded. Colonoscopy with biopsies was performed in all patients that were examined by two pathologists who did not know the clinical characteristics of the subjects. MC was defined according with the universally accepted histological criteria. Results: 155 patients with IBS-D and 145 with IBS-C were studied. Both groups were matched from the standpoint of age, gender ratio and time course of disease. MC was detected in 28 patients with IBS-D and in one with IBS-C (18% vs. 0.7%, p <0.0001). Fifteen patients with lymphocytic colitis and 14 with collagenous colitis were detected. The endoscopic appearance of the colon mucosa was normal in 20 of the 29 patients with MC (69%). Conclusions: The prevalence of MC in patients with IBS-D was 18%, significantly higher than the one observed in patients with IBS-C. Colonic mucosa had a normal appearance in most of the patients with MC. Systematic biopsies are recommended in patients with IBS-D.     

Sleep-Related Autonomic Disturbances in Symptom Subgroups of Women with Irritable Bowel Syndrome

The objective was to investigate whether predominant symptom patterns in women with irritable bowel syndrome (IBS) affect autonomic activity during sleep. Seventy-five women with IBS underwent a polysomnographic sleep study. Twenty-two of the IBS patients were diarrhea-predominant (IBS-D), 33 were constipation-predominant (IBS-C), and 20 patients had alternating symptoms (IBS-A). Autonomic activity was measured by heart rate variability. The IBS-D group had significant vagal withdrawal compared to the IBS-A group during REM and non-REM sleep (P < 0.05). The IBS-D symptom subgroup had significantly (P < 0.05) greater sympathetic dominance during non-REM than IBS-A patients. Lower abdominal pain correlated with sympathetic dominance during sleep in the IBS-D group (r=0.54, P < 0.01). The IBS-D patients were physiologically distinct with regard to autonomic functioning during sleep compared to the alternating patients, but not the constipated patients. Sleep appears to unmask differences in autonomic activity that may distinguish IBS patients.