liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-6820-0215
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
Show others and affiliations
2019 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 21, article id 101602Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 21, article id 101602
Keywords [en]
Irritable bowel syndrome; Gut epithelial permeability; Resting state fMRI; Brain-gut interactions; Default mode network; Coping skills
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-155612DOI: 10.1016/j.nicl.2018.11.012ISI: 000460337700015PubMedID: 30472166Scopus ID: 2-s2.0-85056893948OAI: oai:DiVA.org:liu-155612DiVA, id: diva2:1297717
Note

Funding Agencies|AFA FOrskning [AFA140417]; County Council of Ostergotland [SLS-693541, SLS-503411]; Region Ostergotland [LIO-700871, LIO-606201, LIO-536281, LIO-514271]; Deutsche Forschungsgemeinschaft [DFG IC 81/1-1]; Bengt-Ihre Fonden

Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-08-29Bibliographically approved
In thesis
1. Peripheral and Central Mechanisms in Irritable Bowel Syndrome: in search of links
Open this publication in new window or tab >>Peripheral and Central Mechanisms in Irritable Bowel Syndrome: in search of links
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Irritable bowel syndrome (IBS) is a chronic visceral pain disorder with female predominance, characterized by recurrent abdominal pain and disturbed bowel habits in the absence of an identifiable organic cause. This prevalent and debilitating disease, which accounts for a substantial economic and individual burden, lacks exact diagnostic tools and effective treatment, since its pathophysiology remains uncertain. The bidirectional and multilayered brain-gut axis is a well-established disease model, however, the interactions between central and peripheral mechanisms along the brain-gut axis remain incompletely understood. One of the welldescribed triggering factors, yet accounting for only a fraction of IBS prevalence, is bacterial gastroenteritis that affects mucosal barrier function. Altered gut microbiota composition as well as disturbed intestinal mucosal barrier function and its neuroimmune regulation have been reported in IBS, however, the impact of live bacteria, neither commensal nor pathogenic, on intestinal barrier has not been studied yet. Furthermore, abnormal central processing of visceral sensations and psychological factors such as maladaptive coping have previously been suggested as centrally-mediated pathophysiological mechanisms of importance in IBS. Brain imaging studies have demonstrated an imbalance in descending pain modulatory networks and alterations in brain regions associated with interoceptive awareness and pain processing and modulation, particularly in anterior insula (aINS), although biochemical changes putatively underlying these central alterations remain poorly understood. Most importantly, however, possible associations between these documented changes on central and peripheral levels, which may as complex interactions contribute to disease onset and chronification of symptoms, are widely unknown.

This thesis aimed to investigate the peripheral and central mechanisms in women with IBS compared to female healthy controls (HC) and to explore possible mutual associations between these mechanisms.

In Paper I, we studied paracellular permeability and passage of live bacteria, both commensal and pathogenic through colonic biopsies mounted in Ussing chambers. We explored the regulation of the mucosal barrier function by mast cells and the neuropeptide vasoactive intestinal polypeptide (VIP) as well as a correlation between mucosal permeability and gastrointestinal and psychological symptoms. We observed increased paracellular permeability and the passage of commensal and pathogenic live bacteria in patients with IBS compared with HC, which was diminished by blocking the VIP receptors as well as after stabilizing mast cells in both groups. Moreover, higher paracellular permeability was associated with less somatic and psychological symptoms in patients.

In Paper II, we aimed to determine the association between colonic mucosa paracellular permeability and structural and resting state functional brain connectivity. We demonstrated different patterns of associations between mucosa permeability and functional and structural brain connectivity in IBS patients compared to HC. Specifically, lower paracellular permeability in IBS, similar to the levels detected in HC, was associated with more severe IBS symptoms and increased functional and structural connectivity between intrinsic brain resting state network and descending pain modulation brain regions. Our findings further suggested that this association between mucosa permeability and functional brain connectivity was mainly mediated by coping strategies.

In Paper III, we investigated putative alterations in excitatory and inhibitory neurotransmission of aINS, as the brain’s key node of the salience network crucially involved in cognitive control, in IBS patients relative to HC and addressed possible connections with both symptoms and psychological factors. We found decreased concentrations of the excitatory neurotransmitter Glx in bilateral aINS in IBS patients compared to HC, while inhibitory neurotransmitter GABA+ levels were comparable. Further, we demonstrated hemisphere-specific associations between abdominal pain, coping and aINS excitatory neurotransmitter concentration.

In conclusion, this thesis broadens the knowledge on peripheral and central mechanisms in IBS and presents novel findings that bring together the ends of brain-gut axis. Our results depict association between mucosal permeability, IBS symptoms and functional and structural connectivity engaging brain regions involved in emotion and pain modulation as well as underlying neurotransmitter alterations.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. p. 95
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1678
National Category
Neurosciences Neurology Gastroenterology and Hepatology Surgery Clinical Science
Identifiers
urn:nbn:se:liu:diva-156669 (URN)10.3384/diss.diva-156669 (DOI)9789176850930 (ISBN)
Public defence
2019-06-05, Berzeliussalen, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-09-02Bibliographically approved

Open Access in DiVA

fulltext(3166 kB)10 downloads
File information
File name FULLTEXT01.pdfFile size 3166 kBChecksum SHA-512
979fb2c6ce27690e848e22467e7d547f36a745f16196a06b60cde3dd4c95dfe04eaabae7425357233c2d4547dc82cbfe23980391f162d47145c0c09ca1f687e4
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records BETA

Witt, Suzanne Tyson

Search in DiVA

By author/editor
Witt, Suzanne TysonBednarska, OlgaKeita, ÅsaIcenhour, AdrianeSöderholm, Johan DEngström, MariaWalter, Susanna
By organisation
Center for Medical Image Science and Visualization (CMIV)Faculty of Medicine and Health SciencesDivision of Surgery, Orthopedics and OncologyDepartment of GastroentorologyDivision of Neuro and Inflammation ScienceDepartment of Surgery in LinköpingDivision of Radiological Sciences
In the same journal
NeuroImage: Clinical
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 10 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 32 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf