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Due to a wide range of symptom patterns, patients with irritable bowel syndrome (IBS) are often subgrouped by bowel habit. However, the IBS subgroup with alternating bowel habits (IBS-A) has been poorly characterized. (i) To determine a set of bowel habit symptom criteria, which most specifically identifies IBS patients with an alternating bowel habit, (ii) to describe IBS-A bowel symptom patterns, and (iii) to compare clinical characteristics among IBS-A, constipation-predominant (IBS-C), and diarrhea-predominant IBS (IBS-D). One thousand one hundred and two Rome I positive IBS patients were analyzed. Three sets of potential criteria for IBS-A were developed and compared by multirater Kappa test. Gastrointestinal, psychological, extraintestinal symptoms, and health-related quality of life were compared in IBS-A, IBS-C, and IBS-D using chi(2) test and analysis of variance (ANOVA). Stool consistency was determined to be the most specific criteria for alternating bowel habits. IBS-A patients reported rapid fluctuations in bowel habits with short symptom flares and remissions. There was a greater prevalence of psychological and extraintestinal symptoms in the IBS-A subgroup compared to IBS-C and IBS-D. No differences were seen between bowel habit subtypes in health-related quality of life. IBS-A patients have rapidly fluctuating symptoms and increased psychological comorbidity, which should be taken into account for clinical practice and clinical trials.

The irritable bowel syndrome (IBS) is found more commonly in women than men. It is more prevalent in patients with chronic fatigue syndrome, fibromyalgia, and chronic pelvic pain, all syndromes characterized by pain and found predominantly in women. This article reviews evidence for a role of biological sex factors and gender on the pathways mediating visceral pain. The effect of gonadal hormones on gastrointestinal motility and the sensory afferent pathway and central processing of visceral stimuli and the contribution of gender role to the clinical presentation are discussed. Although differences in responses to treatment modalities between genders exist, the approach to IBS patients in both genders is quite similar. Nevertheless, a special attention to gender role and stress-related factors should be addressed. New developments in research, outlined in the paper, might bring more gender-specific treatments in the future.

Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut–brain interaction (via the gut–brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut–brain interaction. Psychological comorbidity is common; however, whether or not this predates, or is driven by, symptoms is not clear. Patients with functional gastrointestinal disorders can feel stigmatised, and often this diagnosis is not communicated effectively by physicians, nor is education provided. Prompt identification and treatment of these conditions is crucial as they have a considerable impact on health-care systems and society as a whole because of repeated consultations, unnecessary investigations and surgeries, prescriptions and over-the-counter medicine use, and impaired health-related quality of life and ability to work. Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.

Conventionally, patients with irritable bowel syndrome (IBS) are subgrouped based on their predominant bowel habit. Given the relevance of psychological comorbidity to IBS symptoms, our aim was to explore an alternative approach to subgrouping by incorporating factors beyond stool form and frequency. We collected demographic, symptom, and psychological health data from 1,375 adult subjects in the community who self-identified as having IBS, identifying 2 cohorts meeting either Rome III or Rome IV criteria. In each cohort, we performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot and compared these by visual inspection, describing cluster characteristics. In total, 1,080 individuals met the Rome III criteria for IBS, and 811 met the Rome IV criteria. In both cohorts, a 7-cluster model was the optimum solution, and the characteristics of the clusters were almost identical between Rome III and IV. Four clusters were defined by the pattern of gastrointestinal symptoms (loose stools and urgency or hard stools and bloating), further differentiated by the presence of abdominal pain not relieved by defecation, and by the extent of psychological comorbidity. Two clusters had below-average gastrointestinal symptoms, differentiated by the extent of psychological comorbidity. The final cluster had well-above-average gastrointestinal symptoms and high levels of psychological comorbidity. The proportion of subjects with severe IBS symptom scores, high levels of perceived stress, and high levels of gastrointestinal symptom-specific anxiety was significantly higher in clusters with high psychological comorbidity (P < 0.001). Latent class analysis identified 7 distinct IBS subgroups characterized by varying degrees of gastrointestinal symptoms, extraintestinal symptoms, and psychological comorbidity. Further research is needed to assess whether they might be used to direct treatment.

Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS. We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement. Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met eligibility. No significant difference in global improvement of IBS symptoms was observed at 12 weeks in FMT vs placebo (RR = 0.93; 95% CI 0.48-1.79). Heterogeneity among studies was significant (I = 79%). Subgroup analyses revealed benefits of single-dose FMT using colonoscopy and nasojejunal tubes in comparison with autologous FMT for placebo treatment (number needed to treat = 5, RR = 1.59; 95% CI 1.06-2.39; I = 0%) and a reduction in likelihood of improvement of multiple-dose capsule FMT RCTs (number needed to harm = 3, RR = 0.54; 95% CI 0.34-0.85; I = 13%). Placebo response was 33.7% in nonoral FMT RCTs and 67.8% in capsule FMT RCTs. The Grading of Recommendations Assessment, Development and Evaluation quality of the body of evidence was very low. Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms. There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain 1 . For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved 2 . Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men 1 . Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium 3 – 5 . EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings 3 , 6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation 7 , 8 . Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell–mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell–mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain. Visceral pain and anxiety in mice are found to be associated with gut enterochromaffin cells, and genetic models for eliciting visceral hypersensitivity and studying the sex bias of gut pain are proposed.

ObjectiveOur aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms.DesignWe included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression.ResultsIn all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η2: 0.047–0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05).ConclusionsA gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.

Background Irritable bowel syndrome (IBS) affects 10–15% of adults in the US, and is associated with significant impairment in health-related quality of life (HRQoL); however, information specific to the diarrhea subtype (IBS-D) is lacking. We assessed the impact of IBS-D on HRQoL, work productivity, and daily activities, and the associated indirect costs, among a sample of the US population. Methods Respondents (≥18 years) from the 2012 US National Health and Wellness Survey who reported an IBS-D diagnosis by a physician or symptoms consistent with Rome II criteria for IBS-D were identified as having IBS-D. Controls included respondents without IBS-D or inflammatory bowel disease. HRQoL was assessed via the Short Form 36 Health Survey version 2 questionnaire and summarized into Mental and Physical Component Summary (MCS; PCS) scores and a Short Form-6 dimension (SF-6D) utility score. Work and activity impairment were assessed via the Work Productivity and Activity Impairment Questionnaire: General Health version (WPAI:GH), which measures absenteeism, presenteeism, overall work productivity loss, and daily activity impairment. Indirect costs were calculated using unit cost data from the Bureau of Labor Statistics and variables from the WPAI:GH. Generalized linear models were used to examine differences in health outcomes between respondents with IBS-D and controls, controlling for demographic and health characteristics. Results In total, 66,491 respondents (1102 IBS-D; 65,389 controls) were analyzed. Mean age was 48.7 years; 50% were female. Compared with controls, the IBS-D cohort reported significantly lower HRQoL (mean MCS: 45.16 vs. 49.48; p  < 0.001; mean PCS: 47.29 vs. 50.67; p  < 0.001; mean SF-6D: 0.677 vs. 0.741; p  < 0.001) and greater absenteeism (5.1% vs. 2.9%; p  = 0.004), presenteeism (17.9% vs. 11.3%; p  < 0.001), overall work productivity loss (20.7% vs. 13.2%; p  < 0.001), and activity impairment (29.6% vs. 18.9%; p  < 0.001). Respondents with IBS-D also incurred an estimated $2486 more in indirect costs ($7008 vs. $4522; p  < 0.001). Conclusions Compared with controls, IBS-D is associated with significantly lower HRQoL, greater impairments in work and daily activities, and higher indirect costs, imposing a substantial burden on patients and employers. These findings suggest a significant unmet need exists for effective IBS-D treatments.

Although visceral hypersensitivity is a common feature among patients with irritable bowel syndrome (IBS), studies on somatic sensitivity have given controversial results. To assess visceral sensitivity in response to isotonic rectal distensions and somatic sensitivity at different layers of the body wall (skin, subcutis, and muscle) in patients with IBS and fibromyalgia (FM), within and outside the area of abdominal pain referral. We studied 10 patients with IBS, 5 patients with FM, 9 patients with IBS+FM, and 9 healthy controls. Rectal distensions were performed by increasing tension at 4 g steps up to 64 g or discomfort. Pain thresholds to electrical stimulation were measured within and outside the areas of abdominal pain referral. Patients with IBS and IBS+FM demonstrated rectal hypersensitivity in comparison to controls. The threshold of discomfort was 44 +/- 5 g in IBS and 36 +/- 5 in IBS+FM patients, while patients with FM and healthy controls tolerated all distensions without discomfort. In the areas of pain referral, pain thresholds of all three tissues of the body wall were lower than normal in all patients groups (p < 0.001). In control areas, the pain thresholds were normal in skin, and lower than normal in subcutis and muscle in IBS (p < 0.001). FM and IBS+FM demonstrated somatic hypersensitivity at all sites (p < 0.001 vs healthy). Our observations seem to indicate that, although sharing a common hypersensitivity background, multiple mechanisms may modulate perceptual somatic and visceral responses in patients with IBS and FM.

It is well established that people with irritable bowel syndrome (IBS) have higher levels of anxiety and depression compared with controls. However, the role of these as risk factors is less clearly established. The aims of this systematic review were to investigate: (1) whether anxiety and/or depression predict IBS onset; (2) the size of the relative risk (RR) of anxiety versus depression in IBS onset. Subgroup analyses explored if methodological factors affected the overall findings. Prospective cohort or case-control studies were included if they: (1) focused on the development of IBS in population-based or gastroenteritis cohorts; (2) explored the effects of anxiety and/or depression at baseline as predictors of IBS onset at a future point. In all, 11 studies were included of which eight recruited participants with a gastrointestinal infection. Meta-analyses were conducted. The risk of developing IBS was double for anxiety cases at baseline compared with those who were not [RR 2.38, 95% confidence interval (CI) 1.58-3.60]. Similar results were found for depression (RR 2.06, 95% CI 1.44-2.96). Anxiety and depression seemed to play a stronger role in IBS onset in individuals with a gastrointestinal infection although this could be attributed to other differences in methodology, such as use of diagnostic interviews rather than self-report. The findings suggest that self-reported anxiety and depression provide a twofold risk for IBS onset. There is less support for the role of anxiety or depressive disorder diagnosed using clinical interview. These findings may have implications for the development of interventions focused on IBS prevention and treatment.