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
Studies of barrier function in patients with ulcerative colitis and pouchitis
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
2011 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aim: The cause of ulcerative colitis (UC) is largely unknown. However, there is a presumed genetic component to susceptibility and altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis. There is evidence that the increased intestinal permeability in IBD is partly controlled by delicate intercellular circuits in the colonic tissue linked to the enteric nervous system. Little is, however, known about how this is regulated in detail.

Ileal pouch-anal anastomosis (IPAA) is a good surgical reconstructive option in UC patients after proctocolectomy. However 10-15% of IPAA patients develop a severe and recurrent inflammation in the constructed pouch. The standard treatment for pouchitis is long and/or frequent use of antibiotics. Probiotics have been shown to reduce the risk of recurrence of pouchitis after induction treatment with antibiotics.

The aim was to characterize macromolecular permeability in non inflamed colon of UC and elucidate the role of cholinergic signaling, mast cells and eosinophils in the regulation of the human colonic permeability. Furthermore, we examine the mucosal barrier function in relation to pouchitis, before and after treatment with probiotics.

Material and methods: In the first study 23 UC patients in remission and 53 healthy volunteers were included. Biopsies from the sigmoid colon were assed for macromolecular permeability (horseradish peroxidase (HRP) and 51CrEDTA) and electrophysiology during challenge with carbachol. Experiments were repeated with CRF receptor antagonists, carbachol receptor antagonists and mast cell stabilizers in Ussing chambers. Further, pouch biopsies from 16 IPAA patients with pouchitis and 13 IPAA controls were assed in Ussing chambers for macromolecular permeability and electrophysiology as above. In addition E. coli K12 were used to assess the barrier to bacteria. Biopsies were taken on three occasions; before treatment, after antibiotics and after probiotics. Pouchitis Disease Activity Index (PDAI) was used in all subjects.

Results: Colonic tissues from UC patients had significant increase in permeability to protein antigens compared with controls. Permeability was normalized by atropine, α-helical CRF(9-41) and lodoxamide. Eosinophils were increased in number in UC tissues, expressed M2 and M3 muscarinic receptors and showed immunoreactivity to CRF. In pouchitis patients,  PDAI was significantly improved after treatment with antibiotics and probiotics. There was a significantly enhanced passage of E. coli K12 and HRP in patients with active pouchitis, which was unchanged during treatment with antibiotics, but significantly normalized by probiotics.

Conclusions and discussion: We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in UC patients. Furthermore we found that probiotics restored the increased permeation to E. coli and HRP in patients with pouchitis. Pouchitis, resembling symptoms in active UC, may well constitute a good model to study acquired intestinal barrier dysfunction in IBD.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2011. , 42 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 118
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-70830ISBN: 978-91-7393-058-1 (print)OAI: oai:DiVA.org:liu-70830DiVA: diva2:441953
Presentation
2011-10-14, Carl Johan salen ingång 34, plan 10 Universitetssjukhuset, Campus US, Linköpings Universitet, Linköping, 11:00 (Swedish)
Opponent
Supervisors
Available from: 2011-09-20 Created: 2011-09-20 Last updated: 2011-09-20Bibliographically approved
List of papers
1. Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis
Open this publication in new window or tab >>Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis
Show others...
2011 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 140, no 5, 1597-1607 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND andamp; AIMS: Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropinreleasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. METHODS: Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers (51Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). RESULTS: Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), alpha-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. CONCLUSIONS: We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation.

Place, publisher, year, edition, pages
Elsevier Science B.V. Amsterdam, 2011
Keyword
Intestinal Permeability, Inflammatory Bowel Disease, Immune Response, Stress
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68223 (URN)10.1053/j.gastro.2011.01.042 (DOI)000290028200040 ()
Available from: 2011-05-13 Created: 2011-05-13 Last updated: 2017-12-11
2. Effects of probiotics (Ecologic 825) on barrier function during maintenance treatment for severe pouchitis
Open this publication in new window or tab >>Effects of probiotics (Ecologic 825) on barrier function during maintenance treatment for severe pouchitis
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background : About 10-15% of patients with an ileoanal pouch develop a severe, form of pouchitis that necessitates long and/or frequent use of antibiotics and in rare cases even pouch excision. Probiotics have been shown to reduce the risk of recurrence after induction treatment with antibiotics. The mechanisms behind the positive effects of probiotics are not fully understood. The aim of our study was to examine the mucosal barrier function in relation to pouchitis, before and after treatment with probiotics.

Methods: 16 patients with a history of severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: Once during active pouchitis, second after 4 weeks of treatment with antibiotics until clinical remission and third after eight weeks of probiotic treatment. 13 controls with an ileoanal pouch with no recent history of pouchitis were used. The biopsies were mounted in Ussing chambers and mucosal barrier function was assessed by electrophysiology, transmucosal uptake of E coli K12, permeability to Cr-EDTA and Horseradish peroxidase (HRP). Pouchitis Disease Activity Index (PDAI) was used in all subjects.

Results: PDAI was significantly improved after treatment with antibiotics and probiotics. There was a significant difference in E. coli K12 passage before treatment compared to controls (3.7 units (3.4-8.5) vs 1.7 units (1.0-2.4) p< 0.01). E. coli K12 passage did not change after antibiotic treatment (5.0 units (3.3-7.1) p = ns vs controls). In contrast a significant reduction in bacterial uptake was seen after probiotics (2.2 units (1.8-3.3) p< 0.05). Likewise, a significant normalization of HRP flux was seen after probiotic treatment. Pouchitis did not affect paracellular permability or electrophysiology.

Conclusion: Probiotic treatment restored the increased permeation to E. coli and HRP in patients with chronic pouchitis. This could be an important factor behind the positive effects of probiotics in patients with chronic pouchitis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70829 (URN)
Available from: 2011-09-20 Created: 2011-09-20 Last updated: 2011-09-20Bibliographically approved

Open Access in DiVA

Studies of barrier function in patients with ulcerative colitis and pouchitis(1940 kB)1495 downloads
File information
File name FULLTEXT01.pdfFile size 1940 kBChecksum SHA-512
d7abdb767f81156299c761460b5444cb1bb8a68e5617e396206a2bdf8ff64b8c117392db4846eeb72c67c36bc11b7fbac8c1a752aaf0b129067d201c4923f7d7
Type fulltextMimetype application/pdf
omslag(49 kB)33 downloads
File information
File name COVER01.pdfFile size 49 kBChecksum SHA-512
0ad053e2681b66205be0ae0ee0d690db5275e9de86cdad16faa325df4164faf71630cd54c6afc2228013cd861da16e4acb49dc57df4e1525ffca0fcc5d81bd96
Type coverMimetype application/pdf

Authority records BETA

Persborn, Mats

Search in DiVA

By author/editor
Persborn, Mats
By organisation
SurgeryFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 1495 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

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 196 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