Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.

Background Anxiety or depression, in other words, psychological distress, are common comorbidities in patients with irritable bowel syndrome (IBS), but their interaction with pathophysiological factors and other symptoms are unclear. Methods Patients with IBS (Rome III criteria), thoroughly characterized regarding pathophysiology (colonic transit time, visceral sensitivity, and autonomic nervous system [ANS] function), symptom profile (IBS severity, somatic symptoms, gastrointestinal [GI]‐specific anxiety and fatigue), and quality of life, were explored for differences regarding pathophysiology and symptoms between patients with and without reported psychological distress in univariate and multivariate analyses (Principal Component Analysis [PCA] with Hotelling's T2 and Orthogonal Partial Least Squares‐Discriminant Analysis [OPLS‐DA]). Key Results When using Hospital Anxiety and Depression Scale score ≥8 as cut‐off score, including both borderline and clinically significant cases, 345 (44.9%) out of 769 IBS patients reported anxiety, and 198 (25.7%) depression. In univariate analyses, patients reporting psychological distress demonstrated more severe GI and non‐GI symptoms, fatigue, GI‐specific anxiety and lower quality of life, and differences for some pathophysiological measures. IBS patients with and without reported psychological distress showed significant differences between the multivariate means in symptom reporting (PCA; both P < 0.001), and in pathophysiological measures in patients with and without anxiety (P = 0.018). Visceral hypersensitivity, altered ANS function, more severe GI‐specific anxiety, fatigue, and higher somatic non‐GI symptoms were the factors that most strongly separated patients with and without psychological distress (OPLS‐DA). Conclusions and Inferences Reported anxiety and depression are common in IBS patients, and our study demonstrates that they are interwoven in the complex pathophysiological and clinical picture of IBS.

Nearly 10% of patients with an intestinal bacterial infection report postinfectious symptoms up to 10 years after the infectious event. They represent a clinically important population with high psychiatric comorbidity and somatic symptom burden.

This model-based subgrouping of IBS partly supports the distinction of subgroups based on bowel habits, but additionally distinguishes subgroups with or without co-morbid extraintestinal somatic and psychological symptoms. The resulting groups show specific profiles of symptom combinations.

• Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its etiology and pathophysiology, resulting to date in no specific reliable biomarker being identified.• Large multi-center pan European/World studies carefully phenotyping and characterizing patients may help identify subpopulations with accuracy and consistency, aiding future research and treatment.• This position paper highlights the necessary requirements to standardize the process of selecting and phenotyping IBS patients and how to organize the collection and storage of patient information/samples in such studies. AbstractBackground Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/ blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

Altered bacterial composition and small intestinal bacterial overgrowth (SiBo) may be associated with irritable bowel syndrome (IBS). This study aimed to determine the fecal and mucosa-associated bacterial composition along the gastrointestinal (GI) tract and to assess SIBO in IBS. Bacterial composition of feces, and mucosa of the duodenum and sigmoid colon was determined by 16S rRNAamplicon-sequencing. SIBO was evaluated by bacterial culture of duodenal aspirate, glucose and lactulose breath tests. Mucosal antibacterial gene expression was assessed by PCR Array. The bacterial profiles of feces and the mucosa of sigmoid colon, but not duodenum, differed between IBS patients (n = 17) and HS (n = 20). The IBS specific bacterial profiles were linked to the colonic antibacterial gene expression. Fecal bacterial profile differed between IBS subtypes, while the mucosa-associated bacterial profile was associated with IBS symptom severity and breath tests results at baseline (H 2 and/or cH 4 ≥ 15 ppm). The prevalence of SIBO was similar between IBS patients and HS. This study demonstrates that alterations in the bacterial composition of the sigmoid colon of iBS patients were linked to symptoms and immune activation. While breath tests reflected the mucosa-associated bacterial composition, there was no evidence for high prevalence of SIBO or small intestinal bacterial alterations in IBS.

Background In a previous clinical sample of IBS patients, subgroups characterized by profiles of GI and non‐GI symptoms were identified. We aimed to replicate these subgroups and symptom associations in participants fulfilling IBS diagnostic criteria from a population‐based study and relate them to healthcare utilization. Methods An Internet‐based health survey was completed by general population adults from United States, Canada, and UK. Respondents fulfilling IBS diagnosis (Rome III and IV) were analyzed for latent subgroups using Gaussian mixture model analysis. Symptom measures were derived from validated questionnaires: IBS‐related GI symptoms (Rome IV), extraintestinal somatic symptoms (PHQ‐12), and psychological symptoms (SF‐8). Key Results A total of 637 respondents fulfilled Rome III criteria (average age 46 years, range 18‐87, 66% females) and 341 Rome IV criteria (average age 44, range 18‐77, 64% female) for IBS. Seven subgroups were identified in the Rome III cohort, characterized by profiles of GI symptoms (constipation‐related, diarrhea‐related, and mixed, respectively), and further distinguished by the presence or absence of non‐GI comorbidities. The Rome IV cohort showed five similar but less distinct subgroups with a preponderance of mixed symptom profiles. Higher severity of non‐GI comorbidities was associated with more frequent healthcare visits and medication usage. Conclusions and Inferences In line with previous findings in a clinical IBS cohort, we were able to identify population‐based subgroups characterized by a combination of GI symptoms with the additional distinction made by varying severity of non‐GI symptoms and with differences in healthcare utilization.

Altered ANS function was demonstrated in patients with IBS, and this might be of particular relevance for symptoms in a subset of the patients.