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.     

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.     

Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome

Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10–12 week-term improvement after the rifaximin treatment. Stool samples were collected before and after the treatment, and fecal microbiotic profiles were analyzed by deep sequencing of 16S rRNA, while stool metabolic profiles were studied by hydrogen 1-nuclear magnetic resonance (¹H-NMR) and gas chromatography–mass spectrometry (GC-MS). Of 26 identified phyla, only Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were consistently found in all samples. Bacteroidetes was predominant in fecal samples from HCs and IBS-D and IBS-M subjects, whereas Firmicutes was predominant in samples from IBS-C subjects. Species richness, but not community diversity, differentiated all IBS patients from HCs. Metabolic fingerprinting, using NMR spectra, distinguished HCs from all IBS patients. Thirteen metabolites identified by GC-MS differed HCs and IBS patients. However, neither metagenomics nor metabolomics analyses identified significant differences between patients with and without improvement after treatment.     

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.     

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.     

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome

AIM： To investigate if there are changes in serotonin （5-HT） levels, enterochromaffin （EC） cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome （IBS）. METHODS： Diarrhea-predominant （IBS-D, n = 20）, or constipation-predominant （IBS-C, n = 18） IBS patients and healthy controls （n = 20） underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatographyelectrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells. RESULTS： （1） There were no differences in the number and distribution of EC cells between IBS patients and the normal group. （2） The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 ± 90, 122 ± 54, 61 ± 35 ng/mg protein, respectively, which were all lower than those in the normal group （256 ± 84, 188 ± 91, and 93 ± 45 ng/ mg protein, respectively）, with a significant difference at the jejunum （P 〈 0.05）. There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups （P 〈 0.001）. （3） The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 ± 9.4 and 35.8 ± 5.5/highpower field （hpf）, respectively, which were significantly more than that in the normal group （29.8 ± 4.4/hpf） （P 〈 0.001）. There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum （38.7 ± 9.4, 35.8 ± 5.5, 29.8 ±4.4/hpf, respectively） than at the duodenum （19.6± 4.7, 18.5 ± 6.3, 19.2 ±3.3/hpf, respectively, P 〈 0.001）. CONCLUSIO     

Irritable Bowel Syndrome,Particularly the Constipation-Predominant Form,Involves an Increase in Methanobrevibacter smithii,Which Is Associated with Higher Methane Production

Background/AimsBecause Methanobrevibacter smithii produces methane, delaying gut transit, we evaluated M. smithii loads in irritable bowel syndrome (IBS) patients and healthy controls (HC).MethodsQuantitative real-time polymerase chain reaction for M. smithii was performed on the feces of 47 IBS patients (Rome III) and 30 HC. On the lactulose hydrogen breath test (LHBT, done for 25 IBS patients), a fasting methane result ≥10 ppm using 10 g of lactulose defined methane-producers.ResultsOf 47, 20 had constipation (IBS-C), 20 had diarrhea (IBS-D) and seven were not sub-typed. The M. smithii copy number was higher among IBS patients than HC (Log₁₀5.4, interquartile range [IQR; 3.2 to 6.3] vs 1.9 [0.0 to 3.4], p<0.001), particularly among IBS-C compared to IBS-D patients (Log₁₀6.1 [5.5 to 6.6] vs 3.4 [0.6 to 5.7], p=0.001); the copy number negatively correlated with the stool frequency (R=−0.420, p=0.003). The M. smithii copy number was higher among methane-producers than nonproducers (Log₁₀6.4, IQR [5.7 to 7.4] vs 4.1 [1.8 to 5.8], p=0.001). Using a receiver operating characteristic curve, the best cutoff for M. smithii among methane producers was Log₁₀6.0 (sensitivity, 64%; specificity, 86%; area under curve [AUC], 0.896). The AUC for breath methane correlated with the M. smithii copy number among methane producers (r=0.74, p=0.008). Abdominal bloating was more common among methane producers (n=9/11 [82%] vs 5/14 [36%], p=0.021).ConclusionsPatients with IBS, particularly IBS-C, had higher copy numbers of M. smithii than HC. On LHBT, breath methane levels correlated with M. smithii loads.     

Association between anxiety and quality of life in different subgroups irritable bowel syndrome

Introduction: Irritable Bowel Syndrome (IBS) is a frequent functional digestive disorder. Several studies have established the relationship between IBS and anxiety. Also it has been described a negative impact on quality of life in patients who suffer it, but in our country none of these studies have used ROME III criteria for evaluation. Objective: To know the frequency of anxiety in the different subgroups of IBS and its impact on quality of life. Methods: The study was conducted in patients who attended for first time to the outpatient clinic of our hospital for ten months. Adult patients who met the criteria of IBS were included. We applied the SF-36 quality of life questionnaire and the Hamilton anxiety scale. Results: One hundred and two patients who met for IBS criteria were included, of which 85% had anxiety. The IBS-C was the most frequent subgroup. Divided by subgroups, found that 52%, 85.1%, 90% and 80.9% had anxiety for IBS-C, IBS-D, IBS-M and IBS-NC respectively, without significant difference between groups. Patients with anxiety had coger quality of life scores in the categories of physical health, mental health and change in the state of health, (54.2 ± 18 vs. 72 ± 16, 52.8 ± 20 vs. 74 ± 14, 48 ± 28 vs. 59 ± 32) with respect to tose who have no anxiety (p <0.0001, p <0.0001 and p<0.15 respectively). Conclusions: The anxiety was not associated to any subgroup in particular of IBS, the presence of this influenced adversely and significantly on the quality of life of patients who suffer it.     

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.     

肠易激综合征亚型心率变异性分析

目的探讨心率变异性(HRV)分析在IBS亚型中的临床意义。方法选择30例女性IBS患者,分为IBS-D组、IBS-C组、IBS-M组、IBS-U组。同时选择20例健康女性作为对照组。应用SAS、SDS量表对所有对象进行心理状态测评,24 h HRV频域分析指标测定自主神经功能。结果 IBS各亚型组焦虑和抑郁评分均显著高于对照组(P<0.05),同时IBS-C组显著高于其他亚型组(P<0.05)。IBS各亚型组LF/HF显著高于对照组(P<0.05);IBS-C型较其他亚型LF明显升高,HF明显降低,LF/HF比值增高(P<0.05)。结论 IBS-C型患者与其他IBS亚型患者在心理状态和HRV指标上存在差异。     

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome

BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.     

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.     

Diarrhea- and constipation-predominant IBS patients differ in postprandial autonomic and cortisol responses

OBJECTIVE: As the primary link between brain and gut, autonomic and endocrine dysfunction may play a role in the pathophysiology of the irritable bowel syndrome (IBS). The aim of this study was to assess autonomic, endocrine, and symptomatic responses to food intake in diarrhea-predominant and constipation-predominant IBS patients, compared to normals. METHODS: Twelve women with diarrhea-predominant or alternating IBS (IBS-D), 12 women with constipation predominant IBS (IBS-C), and 20 healthy women participated. GI symptoms, saliva cortisol concentration, heart rate, and heart rate variability were assessed at baseline and after a meal. Spectral analysis of heart rate variability was used as a measure of the sympathovagal regulation of the heart rate. RESULTS: Both groups of IBS patients showed a significant postprandial increase in GI symptoms. IBS-D showed a significant increase in the low frequency/high frequency band ratio and a decrease in the high frequency band power during the first postmeal period, which was significantly different, not only from controls, but also from IBS-C. IBS-D also showed a significant postprandial increase in cortisol, which was not evident in controls or IBS-C. There was a significant correlation between the vagal response and the postprandial increase in GI symptoms in IBS-D (r = 0.6, p < 0.05). CONCLUSIONS: These findings support the notion that the IBS symptom groups are characterized by different physiological responses to visceral stimuli, and point to a role of autonomic pathways in IBS symptomatology.     

Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome

BACKGROUNDBile acids (BAs) have attracted attention in the research of irritable bowel syndrome with predominant diarrhea (IBS-D) due to their ability to modulate bowel function and their tight connection with the gut microbiota. The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations. We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome.AIMTo investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota.METHODSFifty-five IBS-D patients diagnosed according to the Rome IV criteria and twenty-eight age-, sex-, and body mass index-matched healthy controls (HCs) were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital. First, clinical manifestations were assessed with standardized questionnaires, and visceral sensitivity was evaluated via the rectal distension test using a high-resolution manometry system. Fecal primary BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), secondary BAs including deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) as well as the corresponding tauro- and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between fecal BAs with clinical features and gut microbiota were explored.RESULTSFecal CA (IBS-D: 3037.66 [282.82, 6917.47] nmol/g, HC: 20.19 [5.03, 1304.28] nmol/g; P < 0.001) and CDCA (IBS-D: 1721.86 [352.80, 2613.83] nmol/g, HC: 57.16 [13.76, 1639.92] nmol/g; P < 0.001) were significantly increased, while LCA (IBS-D: 1621.65 [58.99, 2396.49] nmol/g, HC: 2339.24 [1737.09, 2782.40]; P = 0.002] and UDCA (IBS-D: 8.92 [2.33, 23.93] nmol/g, HC: 17.21 [8.76, 33.48] nmol/g; P = 0.025) were significantly decreased in IBS-D patients compared to HCs. Defecation frequency was positively associated with CA (r = 0.294, P = 0.030) and CDCA (r = 0.290, P = 0.032) and negatively associated with DCA (r = −0.332, P = 0.013) and LCA (r = −0.326, P = 0.015) in IBS-D patients. In total, 23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test. The first sensation threshold was negatively correlated with CDCA (r = −0.459, P = 0.028) in IBS-D patients. Furthermore, the relative abundance of the family Ruminococcaceae was significantly decreased in IBS-D patients (P < 0.001), and 12 genera were significantly lower in IBS-D patients than in HCs (P < 0.05), with 6 belonging to Ruminococcaceae. Eleven of these genera were negatively correlated with primary BAs and positively correlated with secondary BAs in all subjects.CONCLUSIONThe altered metabolism of BAs in the gut of IBS-D patients was associated with diarrhea and visceral hypersensitivity and might be ascribed to dysbiosis, especially the reduction of genera in Ruminococcaceae.     

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.     

美沙拉嗪联合马来酸曲美布汀治疗肠易激综合征患者的临床疗效观察

目的评估美沙拉嗪联合马来酸曲美布汀治疗肠易激综合征(IBS)患者的临床疗效。方法根据罗马Ⅲ诊断标准纳入2014年10月至2016年6月在上海市嘉定区中心医院就诊的腹泻型IBS(IBS-D)和便秘型IBS(IBS-C)患者各40例。40例IBS-D患者随机分为美沙拉嗪+马来酸曲美布汀组和马来酸曲美布汀组,每组各20例;40例IBS-C患者随机分为美沙拉嗪+马来酸曲美布汀组和马来酸曲美布汀组,每组各20例。同期选择20名健康体检者作为正常对照。治疗前后均使用肠易激严重程度评分系统(IBSSS)和医院焦虑抑郁量表(HADS)评估患者的临床疗效和情绪障碍的严重程度。结果研究过程中未观察到严重的药物相关不良反应。在IBS-D患者中,美沙拉嗪+马来酸曲美布汀组经过4周治疗后,IBSSS总分由基线时的(194.5±62.6)分下降至(136.3±47.2)分(P0.000 1),而马来酸曲美布汀单药组则由治疗前的(207.3±49.2)分下降至治疗后的(197.5±47.8)分(P=0.01);在IBS-C患者中,美沙拉嗪+马来酸曲美布汀组经过4周治疗后,IBSSS总分由基线时的(245.8±70.4)分下降至(231.3±65.0)分(P=0.005)。基线状态时,IBS患者组的焦虑和(或)抑郁评分均高于健康对照组(P0.000 1)。在IBS-D患者中,美沙拉嗪+马来酸曲美布汀组经过4周治疗后,焦虑和抑郁评分分别由基线时的(11.9±4.1)分下降至(11.3±4.1)分(P=0.019)、(13.6±4.7)分下降至(12.5±4.5)分(P=0.002 6)。结论美沙拉嗪联合马来酸曲美布汀治疗可改善IBS患者,尤其是IBS-D患者的临床症状和精神心理障碍。     

Symptom differences in moderate to severe IBS patients based on predominant bowel habit

OBJECTIVE: We sought to determine if irritable bowel syndrome (IBS) patients with different bowel habit predominance differ in self-reported viscerosensory symptoms related to the upper and lower gastrointestinal (GI) tract, somatosensory symptoms, and constitutional functions. METHODS: Six hundred and twenty-five Rome criteria-positive IBS patients completed a bowel symptom questionnaire (BSQ), psychological symptom checklist (SCL-90), and health status (SF-36). Bowel habit predominance for IBS patients was determined using the Rome criteria for functional constipation (IBS-C; n = 140) and functional diarrhea (IBS-D; n = 216). The BSQ included questions about viscerosensory symptoms of the upper (chest pressure, bloating, fullness, early satiety, nausea) and lower GI tract (bloating, pain, incomplete evacuation), somatosensory symptoms related to the musculoskeletal system (pain in neck/shoulders, lower back/hip, muscles/joints), and constitutional functions (sleep, appetite, libido). Analysis was further conducted between the IBS-C and IBS-D patients, controlling for gender and quality of sleep, and using the Bonferroni correction to control for multiple comparisons. RESULTS: Female gender was more prevalent among IBS-C than IBS-D (77% vs 56.1%, p < 0.01), whereas age did not differ (40.2 +/- 1.2 yr vs 39.5 +/- 1.0 yr). Symptoms referred to the upper GI were more prevalent in IBS-C than IBS-D: early satiety (56.7% vs 33.9%, p < 0.004), fullness (63.2% vs 38.5%, p < 0.05), and a trend for upper bloating (80.3 vs 62.6%). IBS-C patients reported higher severity ratings for lower GI bloating (p < 0.001). IBS-C more commonly reported musculoskeletal symptoms (92.2% vs 75.4%, p < 0.001), as well as impairment in sleep (31.3 vs 17.5%, p < 0.009), appetite (35.0% vs 18.4%, p < 0.015) and sexual function (45.2% vs 33.1%, p < 0.0021). There were no differences in SCL-90 and SF-36 scores. CONCLUSIONS: Compared with the IBS-D group, the IBS-C patients show greater prevalence of a wide range of symptoms referred to the upper and lower abdomen, musculoskeletal, and constitutional functions. These findings may be related to differences in autonomic or perceptual responses to visceral and somatic stimuli, and are likely to have implications for treatment responses in the two subgroups.     

Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome

BACKGROUNDFaecal microbiota transplantation (FMT) seems to be a promising treatment for irritable bowel syndrome (IBS) patients. In Western countries (United States and Europe), there is a female predominance in IBS. A sex difference in the response to FMT has been reported recently in IBS patients.AIMTo investigate whether there was a sex difference in the response to FMT in the IBS patients who were included in our previous randomized controlled trial of the efficacy of FMT.METHODSThe study included 164 IBS patients who participated in our previous randomized controlled trial. These patients had moderate-to-severe IBS symptoms belonging to the IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant) and IBS-M (mixed) subtypes, and had not responded to the National Institute for Health and Care Excellence (NICE)-modified diet. They belonged in three groups: placebo (own faeces), and active treated group (30-g or 60-g superdonor faeces). The patients completed the IBS severity scoring system (IBS-SSS), Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. The faecal bacteria profile and dysbiosis were determined using the 16S rRNA gene polymerase chain reaction DNA amplification covering V3-V9; probe labelling by single nucleotide extension and signal detection. The levels of short-chain fatty acids (SCFAs) were determined by gas chromatography and flame ionization.RESULTSThere was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with diarrhoea-predominant (IBS-D) than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT.CONCLUSIONThere was no sex difference in the response to FMT among IBS patients with moderate-to-severe symptoms who had previously not responded to NICE-modified diet. However, female patients with IBS-D respond better and have higher reduction of symptoms than males after FMT.