Effect of acute physical and psychological stress on gut autonomic innervation in irritable bowel syndrome

BACKGROUND & AIMS: Stress is an important causative factor in irritable bowel syndrome (IBS). It remains unknown whether stress-related changes in gut function are mediated by altered autonomic efferent gut-specific innervation. We studied the effect of acute physical and psychological stress on autonomic innervation and visceral sensitivity in healthy volunteers and patients with IBS. METHODS: Twenty-four patients (20 women) with constipation-predominant IBS and 12 healthy volunteers (8 women) underwent either physical (cold water hand immersion) or psychological (dichotomous listening) stress on separate occasions. Assessments included stress perception (visual analogue scale), gut-specific autonomic innervation (rectal mucosal blood flow [RMBF] by laser Doppler flowmetry), and viscerosomatic sensitivity (anal and rectal electrosensitivity). RESULTS: Patients with IBS had a heightened baseline perception of stress (P < .01). RMBF decreased during physical stress (29.6% +/- 2.8% and 28.7% +/- 3.9%) and psychological stress (24.4% +/- 2.1% and 23.5% +/- 4.3%) in patients with IBS and controls, respectively (mean +/- SEM). During physical stress, rectal perception (23.2% +/- 6% vs .6% +/- 3% [IBS vs control group, P < .05]) and rectal pain thresholds (27.0% +/- 4% vs 1.3% +/- 5%, P < .001) decreased in patients with IBS only. Psychological stress reduced thresholds for rectal perception (19.4% +/- 6% vs 8% +/- 6%, P < .01) and rectal pain (28.4% +/- 4% vs 3.4% +/- 3.8%, P < .001) in patients with IBS only. Acute stress elevated anal perception thresholds in patients with IBS but not controls (physical stress: 14.7% +/- 14% vs -9.3% +/- 11%, P < .05; psychological stress: 24.7% +/- 9% vs 11% +/- 11%, P < .05). CONCLUSIONS: Acute stress alters gut-specific efferent autonomic innervation in both controls and patients with IBS, although normalization is delayed in IBS. By contrast, only patients with IBS show heightened visceral sensation, suggesting involvement of a different regulatory mechanism, either central or peripheral.     

Is there an association between GNbeta3-C825T genotype and lower functional gastrointestinal disorders?

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

不同层次医学生肠易激综合征发病情况及其与精神因素的关系

目的了解不同层次医学生肠易激综合征(IBS)患病率及其与精神因素的关系。方法对同济医学院160名本科生和153名研究生进行问卷调查。采用胃肠道健康状况调查表,以罗马Ⅱ诊断标准作为IBS患病选择标准;抑郁自评表(SDS)、焦虑自评表(SAS)进行自我评定。结果(1)医学本科生中腹痛累计时间、腹痛程度、腹胀程度、大便异常累计时间评分高于硕士生(P<0.05);女生高于男生(P<0.05);(2)肠易激综合征的总患病率为13.42%,其中本科生为16.25%,硕士生为10.46%,男生12.26%,女生14.56%,但不同层次医学生、男女生之间比较差异均无显著性(P值分别为0.133和0.602);(3)不同层次医学生焦虑和抑郁情绪评分无显著差异(P>0.05),但女生抑郁评分高于男生(P=0.009);IBS相关症状累计时间与严重程度的评分均与心理测试评分呈显著正相关(P=0.000);达到IBS诊断标准的学生焦虑和抑郁的评分明显高于未达到诊断标准者(P=0.000)。结论医学本科生中IBS相关肠道症状发生率高于硕士生,但不同层次医学生肠易激综合征患病率无显著差异,肠易激综合征相关症状及发病与精神因素有关。     

肠易激综合征患者肠黏膜中褪黑素受体的表达及其临床意义

目的探讨肠易激综合征（irritable bowel syndrome，IBS）患者结肠黏膜中褪黑素受体（melatonin receptor，MR）的表达情况及其与肠易激综合征临床症状的相关性。方法用免疫组化法，检测正常对照20例、腹泻型肠易激综合征（diarrhea-predominant IBS，D-IBS）23例、便秘型肠易激综合征（constipation-predominant IBS，C-IBS）20例结肠黏膜中MR的表达情况。使用JEDA801D形态学图像分析系统，测量阳性表达面积及光密度（opacity density，OD）。结果MR在黏膜层含量较多，黏膜下层含量较少。回盲部和乙状结肠MR阳性面积及OD值表现为：D-IBS明显高于正常对照组（P〈0．05），正常对照组明显高于C-IBS（P〈0．05）。与同组IBS乙状结肠相比，回盲部阳性面积增高（P〈0．05）；OD值无明显差异。结论MR在D-IBS中高表达，在C-IBS中低表达，说明MR对IBS患者胃肠道运动有一定影响。     

A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders

BACKGROUND & AIMS: Irritable bowel syndrome, interstitial cystitis, and other chronic pelvic pain (CPP) disorders often occur concomitantly. Neural cross-talk may play a role in the overlap of CPP disorders via the convergence of pelvic afferents. We investigated the hypothesis that afferent irritation of one pelvic organ may adversely influence and sensitize another via neural interactions. METHODS: We measured pelvic organ smooth muscle and striated muscle reflexes during micturition and colorectal distention (CRD) in urethane-anesthetized rats. The effects of acute cystitis on distal colonic sensory thresholds to CRD and the effects of acute colonic irritation on micturition parameters were assessed. RESULTS: External urethral sphincter (EUS) electromyography (EMG) was typical for the rat, with phasic firing during micturition. External anal sphincter EMG also showed phasic firing during micturition in synchrony with EUS activity but, in addition, showed both tonic bursts and phasic firing independent of EUS activity. Before bladder irritation, graded CRDs to 40 cm H2O produced no notable changes in abdominal wall EMG activity. Following acute bladder irritation, dramatic increases in abdominal wall EMG activity in response to CRD were observed at much lower distention pressures, indicating colonic afferent sensitization. Analogously, following acute colonic irritation, bladder contraction frequency increased 66%, suggesting sensitization of lower urinary tract afferents. CONCLUSIONS: We report compelling evidence of bidirectional cross-sensitization of the colon and lower urinary tract in a novel experimental model. This cross-sensitization may account for the substantial overlap of CPP disorders; however, further studies are needed to fully characterize these pathways.     

G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia

BACKGROUND & AIMS: In patients with functional dyspepsia, altered alpha-adrenoreceptor function and depression are prevalent, features that are linked to a G-protein beta 3 (GNB3) subunit gene polymorphism (C825T). We aimed to assess the association of specific G-protein beta 3 subunit genotypes with functional dyspepsia. METHODS: In study A, abdominal symptoms were assessed in 67 patients with unexplained, upper abdominal symptoms and 259 consecutive blood donors with and without abdominal symptoms. In study B, a further 56 patients with functional dyspepsia and 112 age- and sex-matched healthy controls from a blood donor population study were evaluated. Genomic DNA was isolated from buccal swabs and genotyping of the C825T polymorphisms was performed by polymerase chain reaction and restriction analysis. RESULTS: In the blood donors with no abdominal symptoms in study A (controls, n = 161), genotype distribution was 17 TT, 77 TC, and 67 CC. In blood donors and patients with unexplained abdominal symptoms, genotype distribution was 22 TT, 54 TC, and 89 CC (P = 0.007 vs. controls). In study B, the genotype distribution in functional dyspepsia patients was 4 TT, 18 CT, and 34 CC compared with 4 TT, 62 CT, and 46 CC in the controls (P < 0.02). Combining studies A and B, the odds ratio (OR) adjusted for age and sex for upper abdominal symptoms associated with the CC genotype was 2.2 (95% confidence interval [CI]: 1.4-3.3), compared with subjects with TC and TT genotype carrying an allele. CONCLUSIONS: Homozygous GNB3 825C carrier status is associated with unexplained predominantly upper abdominal symptoms.     

认知治疗联合益生菌、匹维溴胺治疗腹泻型肠易激综合征的临床研究

目的本研究试图评价应用认知治疗联合益生菌、匹维溴胺治疗腹泻型肠易激综合征(diarrhea-preclomnant irritable bowelsyndrons,D-IBS)的有效性和安全性。方法符合罗马Ⅲ标准的90例D-IBS患者接受认知治疗、匹维溴胺(50 mg/次,3次/d)、双岐三联活菌制剂(粪链球菌、嗜酸乳杆菌、双歧杆菌3种肠道固有菌的活菌制剂)(420 mg/次,3次/d)共8周,分别记录治疗前后患者SF-36生活质量评分和症状积分以评价疗效;治疗前后对粪便菌丛进行记数,对粪便中5种细菌进行培养并对集落形成单位进行记数;治疗前后用不透X线标志物测定全结肠通过时间来评价结肠运输时间的变化;应用SPSS软件对试验数据进行统计学分析。结果有81例患者完成了本研究;试验过程中未发现不良反应;对于D-IBS患者的治疗,认知治疗联合匹维溴胺、益生菌的总有效率达88.9%,症状改善明显尤其是对于腹痛、大便性状的改善;患者生活质量明显改善,躯体疼痛(BP)、总体健康(GH)、活力(VT)、社会功能(SF)、情感职能(RE)和精神健康(MH)维度的积分有显著提高(P<0.05);益生菌能够明显增加肠道双歧杆菌(P<0.01)和乳酸杆菌(P<0.05),明显减少肠球菌(P<0.01)和类杆菌(P<0.05),而肠杆菌无显著变化(P>0.05);结肠运输时间延迟显著(P<0.05)。结论认知治疗联合匹维溴胺和益生菌治疗D-IBS是安全、有效的。     

Altered bile acid metabolism in patients with constipation-predominant irritable bowel syndrome and functional constipation

Objective. Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate whether bile acid synthesis is altered in constipation. Material and methods. Female patients with constipation (23 IBS-C, 4 functional constipation (FC)) were studied and compared with non-constipated subjects (16 IBS-D, 20 healthy women). Body mass index (BMI), blood lipids, lanosterol, sitosterol, colonic transit (oro-anal transit time (OATT), reference=4.3 days) and stool frequency were measured. C4 (7-α-hydroxy-4-cholesten-3-one) levels reflecting bile acid synthesis were measured at 0800 h and 1300 h. Results. When all the groups of constipated and non-constipated subjects were compared, it was found that only stool frequency and OATT differed between groups (p <0.001). When constipated patients were categorized according to OATT, absence of the usual C4 increase at lunchtime was noted in 82% of patients with delayed OATT compared with 17% in subjects with normal OATT (p <0.001). Symptom severity did not differ between groups. A subset of the patients with severely delayed OATT had markedly elevated C4 levels. Conclusions. Patients with IBS-C and FC have marked changes in bile acid synthesis in relation to colonic transit. The diurnal rhythm is altered in the slow transit colon when there is no C4 peak at lunchtime. Alterations in bile acid metabolism may be implicated in the pathophysiology of constipation.     

Inflammatory bowel disease versus irritable bowel syndrome: a hospital‐based,case‐control study of disease impact on quality of life

Background: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are intestinal diseases perceived differently by patients and doctors: the former is considered essentially as an ‘organic’ disease (i.e. an illness in which the role of stress or psychological factors is at best secondary to the disease itself), whereas the latter is acknowledged as a ‘functional’ disorder (i.e. illness thought to be more in the ‘mind’ than in the body of the patient). Accordingly, the respective impact of the two diseases on patients' health‐related quality of life (HRQOL) is perceived to be very different. We aimed to compare the relative impact of the disease on HRQOL, psychological profile and perceived burden of stressful life events in two groups of outpatients suffering from IBS and IBD and attending our outpatient department at an Italian university hospital. Eighty patients with IBD (26 with ulcerative colitis and 54 with Crohn disease) and 85 controls with IBS formed the patient samples of the study. Methods: Three questionnaires were given to the patients while they were attending the outpatient department because of their previously diagnosed disease, namely the SF‐36 (a generic well‐validated tool for measuring HRQOL), the SCL‐90 (for assessing the psychological profile of patients), and the Holmes &; Rahe schedule (for the assessment of stressful life experiences). The results were then compared by means of analysis of variance (ANOVA) and Bonferroni‐adjusted t test, when appropriate. Results: HRQOL appeared to be similarly reduced in both disease groups (SF‐36 overall mean value: 58.2?±?16.1 in IBS patients versus 56.4?±?22.3 in IBD patients; P?>?0.05) in comparison with normative Italian data. Furthermore, the overall severity of psychological symptoms was not statistically different between patients suffering from IBD versus IBS, as shown by SCL‐90 mean scores of 0.89?±?0.45 versus 0.83?±?0.48, respectively (P?>?0.05). On the contrary, the severity of recent stressful life experiences was perceived to be higher by IBS than by IBD patients (mean SRE score: 110.8?±?110.2 versus 61.6?±?78.8; P?Conclusion: Our study supports the notion that, at least in referral centres, patients with IBS show health‐related quality of life, psychological distress and recent occurrence of stressful life events of severity at least comparable with age‐matched IBD patients.