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- Bednarska, Olga, et al.
(författare)
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Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
- 2017
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 153:4, s. 948-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.
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- Icenhour, Adriane, et al.
(författare)
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Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome
- 2017
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Ingår i: NeuroImage. - : ELSEVIER SCI LTD. - 2213-1582. ; 15, s. 449-457
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Tidskriftsartikel (refereegranskat)abstract
- Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N= 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS.
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- Walter, Susanna, et al.
(författare)
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Su2113 High-Intense Rectal Urgency and Its Representation in the Brain
- 2013
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Konferensbidrag (refereegranskat)abstract
- Background: Several brain imaging studies have demonstrated that visceral distensions activate the insular cortex but there is limited knowledge about which subregions of the insula underpin the feeling of rectal urgency. An isobaric rectal balloon distension can be subdivided into the inflation phase when pressure is rising (rise) and a stable phase, when the pressure is constant. The rise phase is characterized by a more distinct sensation of urgency (Akervall et al., 1988). We aimed to study the BOLD response during the rise phase of a standardized rectal distension in subregions of the insula, in healthy controls.Method:Twenty right-handed female healthy volunteers (mean age 32.2 yrs, range 21-54) were included. Rectal pressure sensory thresholds were determined before functional Magnetic Resonance Imaging (fMRI) while the subjects were placed in the MR scanner. Blood Oxygen Level Dependent (BOLD) signals were measured during the rise periods (6.6-7.2 sec) of 20 rectal distensions (45mmHg). Regions of interest (ROIs) included 10 insula subregions: Left (L) and right (R) anterior ventral, anterior dorsal, posterior ventral, posterior dorsal and mid insula. Results were reported as significant if peak p-value were, 0.05 with familywise error (FWE) correction in the ROIs.Results: The mean values for rectal sensory thresholds for first sensation, first sensation of urgency and maximum tolerable distension were 16 mmHg (SD 3.9), 28mmHg (SD 6.2) and 55 mmHg (SD 12.3), respectively. Complete fMRI data were available from 18 subjects. The rise period of the rectal distension generated significant BOLD activation in the right hemisphere in the anterior dorsal, anterior ventral, mid and posterior ventral parts of the insula. On the left side BOLD activity was generated in mid, posterior ventral and posterior dorsal parts of the insula but not in the anterior insula. Akervall S et al, 1988, Manovolumetry: A new method for investigation of anorectal function. Gut 29:614-623.
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- Witt, Suzanne Tyson, 1979-, et al.
(författare)
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Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
- 2019
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Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.
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