BACKGROUND & AIMS Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. METHODS Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 weeks. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed. RESULTS FMPP intake was associated with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) containing affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity, which could explain the observed differences in activity during the task. CONCLUSIONS Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation.

SUMMARYBackground: Anxiety related to gastrointestinal sensations, symptoms or the contexts in which these may occur is thought to play a significant role in the pathophysiology as well as in the health outcomes of patients with irritable bowel syndrome. Aim: To develop a valid and reliable psychometric instrument that measures gastrointestinal symptomspecific anxiety. Methods: External and internal expert panels as well as a patient focus group evaluated a large pool of potential item stems gathered from the psychological and gastrointestinal literature. Potential scale items were then administered to 96 patients diagnosed with

Background and Aims The responsiveness of the central nervous system (CNS) is altered in patients with irritable bowel syndrome (IBS). However, due variations in experimental paradigms, analytic techniques, and reporting practices, little consensus exists on brain responses to visceral stimulation. We aimed to identify brain regions consistently activated by supraliminal rectal stimulation in IBS patients and healthy subjects (controls), by performing a quantitative meta-analysis of published studies. Methods Significant foci from with-in group statistical parametric maps were extracted from published neuroimaging studies that employed rectal distension. Voxel-based activation likelihood estimation was applied, pooling the results and comparing them across groups. Results Across studies, there was consistent activation in regions associated with visceral afferent processing (thalamus, insula, anterior mid-cingulate) among IBS patients and controls, but considerable differences in the extent and specific location of foci. IBS patients differed from controls in: 1) More consistent activations in regions associated with emotional arousal [pregenual anterior cingulate cortex (pACC), amygdala]; 2) Activation of a midbrain cluster, a region playing a role in endogenous pain modulation. Controls showed more consistent activation of the medial and lateral prefrontal cortex. Conclusions Patients with IBS have greater engagement of regions associated with emotional arousal and endogenous pain modulation, but similar activation of regions involved in processing of visceral afferent information. Controls have greater engagement of cognitive modulatory regions. These results support a role for CNS dysregulation in IBS. These findings provide specific targets for guiding development of future neuroimaging protocols to more clearly define altered brain-gut interactions in IBS.

Overall, the VSI demonstrated excellent psychometric properties providing further support for its use in mechanistic studies of the role of anxiety in irritable bowel syndrome presentation.

Despite an extensive body of reported information about peripheral and central mechanisms involved in the pathophysiology of IBS symptoms, no comprehensive disease model has emerged that would guide the development of novel, effective therapies. In this Review, we will first describe novel insights into some key components of brain–gut interactions, starting with the emerging findings of distinct functional and structural brain signatures of IBS. We will then point out emerging correlations between these brain networks and genomic, gastrointestinal, immune and gut-microbiome-related parameters. We will incorporate this new information, as well as the reported extensive literature on various peripheral mechanisms, into a systems-based disease model of IBS, and discuss the implications of such a model for improved understanding of the disorder, and for the development of more-effective treatment approaches in the future.

Background & Aims Several studies have examined structural brain changes associated with chronic pain syndromes, including irritable bowel syndrome (IBS), but study sample sizes have been small and heterogeneous. Methods We used magnetic resonance imaging (MRI)-based techniques, voxel-based morphometry, and cortical thickness analysis, to examine brain anatomical differences in a relatively large, tightly screened sample of IBS patients (n=55); we compared data with that from healthy individuals (controls, n=48). Results IBS was associated with decreased gray matter density (GMD) in widespread areas of the brain, including medial prefrontal and ventrolateral prefrontal cortex, posterior parietal cortex, ventral striatum, and thalamus. Compared with controls, we observed increased GMD in patients with IBS in the pregenual anterior cingulate cortex and the orbitofrontal cortex, as well as trends in the posterior insula/secondary somatosensory cortex, (para)hippocampus, and left dorsolateral prefrontal cortex. In accounting for anxiety and depression, we found that several of the regions involved in affective processing no longer differed between patients with IBS and controls, whereas the differences in prefrontal and posterior parietal cortices remained. The areas of decreased GMD associated with IBS were largely consistent across clinical subgroups, based on predominant bowel habit and pain predominance of symptoms. There were no overall or regional differences in cortical thickness between patients with IBS and controls. Conclusions Changes in density of gray matter among regions involved in cognitive/evaluative functions are specifically observed in patients with IBS, whereas changes in other areas of the brain can be accounted for explained by levels of anxiety and depression.

BackgroundPreclinical and clinical evidence supports the concept of bidirectional brain-gut microbiome interactions. We aimed to determine if subgroups of irritable bowel syndrome (IBS) subjects can be identified based on differences in gut microbial composition, and if there are correlations between gut microbial measures and structural brain signatures in IBS.MethodsBehavioral measures, stool samples, and structural brain images were collected from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. The metagenomic content of samples was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T scanner, and morphological measures were computed for 165 brain regions.ResultsUsing unweighted Unifrac distances with hierarchical clustering on microbial data, samples were clustered into two IBS subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest classifier provided further support for the differentiation of IBS1 and HC groups. Microbes belonging to the genera Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification. Clinical features distinguishing the groups included a history of early life trauma and duration of symptoms (greater in IBS1), but not self-reported bowel habits, anxiety, depression, or medication use. Gut microbial composition correlated with structural measures of brain regions including sensory- and salience-related regions, and with a history of early life trauma.ConclusionsThe results confirm previous reports of gut microbiome-based IBS subgroups and identify for the first time brain structural alterations associated with these subgroups. They provide preliminary evidence for the involvement of specific microbes and their predicted metabolites in these correlations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-017-0260-z) contains supplementary material, which is available to authorized users.

Patients with mild chronic inflammation of the rectum or ileum have reduced perceptual responses to rectosigmoid distension compared to patients with irritable bowel syndrome (IBS). The current study sought to identify differences in regional cerebral blood flow (rCBF) during rectal distension, which might correspond to these perceptual differences. In 8 male ulcerative colitis (UC) patients with quiescent disease, 7 male IBS patients and 7 healthy male controls, rCBF was assessed using 15O-water positron emission tomography at baseline and during actual and anticipated but undelivered rectal distensions. No group differences were seen in anterior insula and dorsal anterior cingulate cortex (dACC), two regions consistently activated by painful intestinal stimuli. However, IBS patients showed greater activation of the amygdala, rostroventral ACC, and dorsomedial frontal cortical regions. In contrast, no significant differences were observed between UC and controls. When these two non-IBS groups were combined, functional connectivity analyses showed that right lateral frontal cortex (RLFC) activation positively correlated with activation of the dorsal pons/periaqueductal gray, a key region involved in endogenous pain inhibition. According to the connectivity analysis, this effect was mediated by inhibition of medial frontal cortex by the RLFC. Chronic colonic inflammation is not necessarily associated with increased visceral afferent input to the brain during rectal distension. In the sample studied, the primary difference between functional and quiescent inflammatory disease of the colon was in terms of greater activation of limbic/paralimbic circuits in IBS, and inhibition of these circuits in UC and controls by the RLFC.