Background and aimsEvidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function.MethodsWe performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function.ResultsWe found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks.ConclusionsIn a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS—these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.Electronic supplementary materialThe online version of this article (10.1186/s40168-019-0656-z) contains supplementary material, which is available to authorized users.

Background and objective: Psychological states may interfere with visceral sensitivity. Here we investigate associations between psychosocial factors and visceral sensitivity in irritable bowel syndrome (IBS). Methods: Two IBS patient cohorts (Cohort 1: n ¼ 231, Rome II; Cohort 2: n ¼ 141, Rome III) underwent rectal barostat testing, and completed questionnaires for anxiety, depression, somatization, and abuse. The associations between questionnaire measures and visceral sensitivity parameters were analyzed in three-step general linear models (step1: demographic and abuse variables; step 2: anxiety and depression; step 3: somatization). Results: Cohort 1. Pain threshold was positively associated with age and female gender, and negatively with adult sexual abuse and somatization. Pain referral area was negatively associated with age and positively with somatization and GIspecific anxiety, the latter effect mediated by somatization. Cohort 2. Pain threshold was positively associated with age and male gender, and negatively with adult sexual abuse. Pain intensity ratings were positively associated with somatization, female gender and depression, the latter effect mediated by somatization. Conclusion: Somatization is associated with most visceral sensitivity parameters, and mediates the effect of some psychological factors on visceral sensitivity. It may reflect a psychobiological sensitization process driving symptom generation in IBS. In addition, abuse history was found to independently affect some visceral sensitivity parameters.

Hypersensitive IBS patients are characterized by increased perception of pain, but also of non-painful sensations. Psychological factors increase the perception of painful sensations in hypersensitive patients only, whereas non-painful visceral sensations were exaggerated in anxious patients regardless of the sensitivity status.

Background: Central sensitization has been suggested as an explanation of the wide range of gastrointestinal and extraintestinal symptoms commonly seen in irritable bowel syndrome (IBS). In this study, the presence and level of central sensitization, and its association to gastrointestinal (GI) symptoms were explored in IBS in comparison with control groups. Methods:We investigated patients with IBS (n = 215), chronic pain disorders (n = 36), and inflammatory bowel disease (IBD) (n = 40) and volunteers without chronic diseases (n = 112). The Central Sensitization Inventory (CSI) was translated and validated in Swedish and used together with the Highly Sensitive Person (HSP) scale to measure the presence and level of central sensitization. Furthermore, severity of GI symptoms (GSRS-IBS and IBS-SSS), and anxiety and depression (HAD) were determined. Key results:The Swedish translation of CSI demonstrated excellent validity. Central sensitization, defined by validated cut-off levels for CSI and HSP, was common in the whole cohort (40% and 28%) and in IBS (57% and 35%). Study participants with central sensitization had more severe GI symptoms, anxiety and depression, than participants without central sensitization. Strong associations were seen between CSI and GI symptom severity in the whole cohort (GSRS-IBS: partial η 2 = 0.455, p < 0.001; IBS-SSS: partial η 2 = 0.408, p < 0.001), with decreasing strength in patients with chronic pain, IBD, IBS, and volunteers. Conclusion and Inferences:Central sensitization was common in IBS and associated with GI symptom severity, but with stronger associations in chronic pain disorders and IBD. This implies that other mechanisms may be of equal or greater importance for GI symptom severity in IBS.

Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.