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Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
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Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
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2013 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 48, no 10, 1136-1144 p.Article in journal (Refereed) Published
Abstract [en]

Objective. The intestinal microbiota plays a substantial role in the pathogenesis of inflammatory bowel disease (IBD). Faecalibacterium prausnitzii (FP) is underrepresented in IBD patients and have been suggested to have anti-inflammatory effects in mice. Increased intestinal permeability is common in IBD but the relationship between FP and intestinal barrier function has not been investigated. Our aim was to study treatment with FP supernatant on intestinal barrier function in a dextran sodium sulfate (DSS) colitis mice model. Material and methods. C57BL/6 mice received 3% DSS in tap water ad libitum during five days to induce colitis. From day 3 the mice received a daily gavage with FP supernatant or broth during seven days. Ileum and colon were mounted in Ussing chambers for permeability studies with Cr-51-EDTA and Escherichia coli K-12. Colon was saved for Western blot analyses of tight junction proteins. Results. DSS-treated mice showed significant weight loss and colon shortening. Gavage with FP supernatant resulted in a quicker recovery after DSS treatment and less extensive colonic shortening. Ileal mucosa of DSS mice showed a significant increase in Cr-51-EDTA-passage compared to controls. Cr-51-EDTA passage was significantly decreased in mice receiving FP supernatant. No significant differences were observed in passage of E. coli K12. Western blots showed a trend to increased claudin-1 and claudin-2 expressions in DSS mice. Conclusions. Supernatant of FP enhances the intestinal barrier function by affecting paracellular permeability, and may thereby attenuate the severity of DSS-induced colitis in mice. These findings suggest a potential role of FP in the treatment of IBD.

Place, publisher, year, edition, pages
Informa Healthcare , 2013. Vol. 48, no 10, 1136-1144 p.
Keyword [en]
dextran sodium sulfate, inflammatory bowel disease, permeability, probiotics, tight junctions
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-99406DOI: 10.3109/00365521.2013.828773ISI: 000324761000005OAI: diva2:656898

Funding Agencies|Swedish Research Council|VR-M: K2012-55X-12618-16-3|

Available from: 2013-10-17 Created: 2013-10-17 Last updated: 2014-08-26
In thesis
1. Role of mast cells and probiotics in the regulation of intestinal barrier function
Open this publication in new window or tab >>Role of mast cells and probiotics in the regulation of intestinal barrier function
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The intestinal mucosa is the largest contact area and one of the most important barriers to the outside environment. It is highly specialized in aiding us digest and absorb nutrients. It is daily exposed to several potentially dangerous substances and microorganisms, which if they were allowed to pass into the body, could give rise to diseases. Throughout the small intestine certain sites specialized in antigen sampling are found. These sites are named Peyer’s patches and are lymphoid follicles. The epithelium covering the Peyer’s patches is called follicle-associated epithelium and is specialized in antigen sampling and uptake. The special epithelium enables presentation of luminal antigen to immune cells in the underlying follicle.

Persistent life stress and stressful life events affect the course of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) through largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immune-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis and Crohns disease. Vasoactive intestinal polypeptide (VIP) and corticotropin-releasing factor have been implicated as important mediators of stress-induced abnormalities in intestinal mucosal functions in animal models. Both of these mediators have been reported to regulate bowel ion secretion in humans during stress and uptake of horseradish peroxidase in rodents. Probiotics have been shown to ameliorate the deleterious effects of stress on intestinal function, but mechanisms remain to be elucidated.

The aim of this thesis was to elucidate whether mast cells play an important role in intestinal barrier function during stress and inflammation. Moreover, we wanted to determine whether probiotics can ameliorate the mucosal barrier integrity during stress and inflammation.

To study the function of mast cells we conducted in vitro experiments on cell lines and ex vivo experiments in Ussing chambers on mouse, rat and human intestinal tissue. The Ussing chamber technique measures electrophysiological properties of the tissue and also gives the possibility to study transcellular and paracellular passage of markers and bacteria. Immunohistology and confocal microscopy have been used to identify mast cells and receptors of interest.

Our results show that stress affects the follicle-associated epithelium barrier by mechanisms involving VIP and mast cells. These findings were corroborated by the localization of VIP receptors on mucosal mast cells. Furthermore, pretreatment with probiotics was effective in protecting the gut against stress-induced intestinal barrier dysfunction and mucosal inflammation. This protection appeared to involve a mast cell and peroxisome proliferatoractivated receptor-γ dependent mechanism.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 62 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1363
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-100770 (URN)10.3384/diss.diva-100770 (DOI)978-91-7519-630-5 (print) (ISBN)
Public defence
2013-12-12, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:15 (Swedish)
Available from: 2013-11-12 Created: 2013-11-12 Last updated: 2013-11-12Bibliographically approved

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Carlsson, Anders H.Yakymenko, OlenaHåkansson, FathimaKeita, Asa V.Soderholm, Johan D.
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Division of Clinical SciencesFaculty of Health SciencesDepartment of Surgery in Linköping
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