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Carlsson, Anders
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Publications (10 of 11) Show all publications
Carlsson, A. H., Yakymenko, O., Olivier, I., Håkansson, F., Postma, E., Keita, A. V. & Soderholm, J. D. (2013). Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis. Scandinavian Journal of Gastroenterology, 48(10), 1136-1144
Open this publication in new window or tab >>Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis
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2013 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 10, p. 1136-1144Article 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
Keywords
dextran sodium sulfate, inflammatory bowel disease, permeability, probiotics, tight junctions
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-99406 (URN)10.3109/00365521.2013.828773 (DOI)000324761000005 ()
Note

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

Available from: 2013-10-17 Created: 2013-10-17 Last updated: 2018-04-27
Carlsson, A. H., Lutgendorff, F., Akkermans, L. M. .., McKay, D. M. & Söderholm, J. D. (2013). Probiotics modulate mast cell degranulation and reduce stress-induced barrier dysfunction in vitro.
Open this publication in new window or tab >>Probiotics modulate mast cell degranulation and reduce stress-induced barrier dysfunction in vitro
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

BACKGROUND: Stress has well-established deleterious effects on intestinal barrier function and stressful life events are known to contribute to the development and perpetuation of inflammatory bowel diseases. Mast cells play a pivotal role in pathogenesis of stressinduced barrier dysfunction due to the release of barrier-disruptive content. Conversely, they also have recently been suggested to contribute to barrier protective properties of probiotics, through the release of 15d-PGJ2 and enhanced epithelial PPAR-γ activity. However, mechanisms remain to be elucidated.

AIM: To study if probiotics can modulate mast cell mediator release, resulting in amelioration of stress-induced barrier dysfunction in vitro.

METHODS: Confluent monolayers of the human colon-derived T84 epithelial cell line were co-cultured with rat basophilic leukemia (RBL)-2H3 mast cells and pretreated with probiotics (125x104 CFU/ml, 1hr) before addition of 100nM CRF to activate mast cells. Release of beta hexosaminidase, TNF-α and 15d-PGJ2 from mast cells was determined. Transepithelial resistance (TER), and permeability to microspheres (0.2μm) were measured over a 24h period. To determine dependence of PPAR-γ, monolayers were incubated with the specific PPAR-γ antagonist T0070907 before treatment with probiotics.

RESULTS: CRF-induced activation of mast cells resulted in decreased TERs and increased permeability to microspheres. Both pretreatment with probiotics and filter-sterilized probiotic supernatant resulted in lower levels of mast cell-released beta hexosaminidase and TNF-α, and increased 15d-PGJ2. Furthermore, probiotics ameliorated epithelial barrier dysfunction in monolayers exposed to CRF-activated mast cells. However, when T84 monolayers were exposed to conditioned medium of CRF-activated mast cells or were incubated with T0070907, probiotics showed little or no effect.

CONCLUSIONS: Probiotics modulate mast cell mediator release to a more barrier protective profile, resulting in amelioration of stress-induced epithelial barrier dysfunction, which is putatively mediated by a PPAR-γ dependent pathway.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-100768 (URN)
Available from: 2013-11-12 Created: 2013-11-12 Last updated: 2014-03-25Bibliographically approved
Lutgendorff, F., Carlsson, A. H., Timmerman, H. M., Akkermans, L. M. .. & Söderholm, J. D. (2013). Protective Effects of Probiotics on Chronic Stress-Induced Intestinal Permeability in Rats are mediated via Mast Cells and PPARγ.
Open this publication in new window or tab >>Protective Effects of Probiotics on Chronic Stress-Induced Intestinal Permeability in Rats are mediated via Mast Cells and PPARγ
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

BACKGROUND: Chronic stress, which may affect in the clinical course of inflammatory and functional bowel diseases, disrupts intestinal barrier function by routes involving mast cells. Probiotics have been shown to ameliorate the deleterious effects of stress on intestinal function, but mechanisms remain to be elucidated. Peroxisome proliferator-activated receptor (PPAR)-γ signaling is activated as an endogenous defense mechanism during chronic stress and evidence suggests that probiotics reduce the degradation of PPAR-γ. As a source of the endogenous agonist for PPAR-γ, 15d-PGJ2, and as an important mediator of the stress response, mast cells may have both a beneficial and a deleterious role in the effects on intestinal function by probiotics.

AIM: Our aim was to study if mast cells contribute to the positive effects of probiotic therapy on intestinal function in a rat model of chronic stress.

METHODS: 32 Mast cell deficient (Ws/Ws) and 32 wild-type (+/+) rats were subjected to water avoidance stress (WAS) or sham stress (SS) 1hr/day for 10 days. Seven days prior to the onset of stress, probiotics (PB, multispecies combination of 10 different lactic acid bacteria) were added to the standard diet (St) in half of the animals. To determine dependence of PPAR-γ, 8 probiotic-fed wild-type rats subjected to WAS were injected daily with the specific PPAR-γ antagonist T0070907. The colonic mucosa was exposed to E. coli HB101 incorporated with green fluorescent protein and permeability was assessed in Ussing chambers. Mesenteric lymph nodes (MLN) were cultured to determine bacterial translocation.

RESULTS: Chronic stress induced a marked increase in ileal permeability to E.coli HB101 in +/+ rats (0.17±0.1 x106CFU/hr in SS/St/++ vs. 2.13±0.4 in WAS/St/++; P<0.001). This breach in barrier integrity was less pronounced in Ws/Ws rats (2.13±0.4 in WAS/St/++ vs. 1.19±0.3 in WAS/St/WsWs; P<0.01). Probiotics prevented stress-induced effects in E.coli HB101 passage only in wild-type rats (82% decrease in +/+ vs. 0% in Ws/Ws rats). Furthermore, only in the presence of mast cells did probiotics reduce the enhanced bacterial translocation to MLNs during chronic stress. In wild-type rats treated with a PPAR-γ antagonist, the barrier protective effects of probiotics were diminished.

CONCLUSIONS: Mast cells acting via a PPAR-γ dependent pathway contribute to the beneficial effects of probiotics on chronic stress-induced mucosal dysfunction in rats.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-100767 (URN)
Available from: 2013-11-12 Created: 2013-11-12 Last updated: 2014-03-25
Carlsson, A. (2013). Role of mast cells and probiotics in the regulation of intestinal barrier function. (Doctoral dissertation). Linköping: Linköping University Electronic Press
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. p. 62
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1363
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-100770 (URN)10.3384/diss.diva-100770 (DOI)978-91-7519-630-5 (ISBN)
Public defence
2013-12-12, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2013-11-12 Created: 2013-11-12 Last updated: 2013-11-12Bibliographically approved
Persborn, M., Gerritsen, J., Wallon, C., Carlsson, A., Akkermans, L. M. & Söderholm, J. D. (2013). The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis. Alimentary Pharmacology and Therapeutics, 38(7), 772-783
Open this publication in new window or tab >>The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis
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2013 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 38, no 7, p. 772-783Article in journal (Refereed) Published
Abstract [en]

Background less thanbrgreater than less thanbrgreater thanA total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. less thanbrgreater than less thanbrgreater thanAim less thanbrgreater than less thanbrgreater thanTo examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. less thanbrgreater than less thanbrgreater thanMethods less thanbrgreater than less thanbrgreater thanSixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanPouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P andlt; 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P andlt; 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanProbiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98215 (URN)10.1111/apt.12451 (DOI)000323843900011 ()
Note

Funding Agencies|Swedish Research Council - Medicine||Research Council of South-East Sweden (FORSS)||County Council of Ostergotland||County Council of Jonkoping||SenterNovem (Agentschap NL), an agency of the Dutch Ministry of Economic Affairs|FND-07013|

Available from: 2013-10-03 Created: 2013-10-03 Last updated: 2017-12-06
Munch, A., Söderholm, J. D., Ost, A., Carlsson, A., Magnusson, K.-E. & Ström, M. (2011). Low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission. ALIMENTARY PHARMACOLOGY and THERAPEUTICS, 33(8), 954-960
Open this publication in new window or tab >>Low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission
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2011 (English)In: ALIMENTARY PHARMACOLOGY and THERAPEUTICS, ISSN 0269-2813, Vol. 33, no 8, p. 954-960Article in journal (Refereed) Published
Abstract [en]

Pandgt;Background Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. Aim To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. Methods The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), potential difference, trans-epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 mu mol/L CDCA or DCA. Results When adding 100 mu mol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3] (P = 0.004 and P = 0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans-epithelial passage of E. coli K12 within 30 min. Conclusions Low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.

Place, publisher, year, edition, pages
Blackwell Publishing Ltd, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67324 (URN)10.1111/j.1365-2036.2011.04611.x (DOI)000288515800011 ()
Available from: 2011-04-08 Created: 2011-04-08 Last updated: 2015-03-12
Ragnarsson, E. G., Schoultz, I., Gullberg, E., Carlsson, A., Tafazoli, F., Lerm, M., . . . Artursson, P. (2008). Yersinia pseudotuberculosis induces transcytosis of nanoparticles across human intestinal villus epithelium via invasin-dependent macropinocytosis. Laboratory Investigation, 88(11), 1215-1226
Open this publication in new window or tab >>Yersinia pseudotuberculosis induces transcytosis of nanoparticles across human intestinal villus epithelium via invasin-dependent macropinocytosis
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2008 (English)In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 88, no 11, p. 1215-1226Article in journal (Refereed) Published
Abstract [en]

Crohns disease is characterized by a defect in intestinal barrier function, where bacteria are considered the most important inflammation-driving factor. Enteric bacteria, including E. coli and Yersinia spp, affect tight junctions in enterocytes, but little is known about bacterial effects on the transcellular pathway. Our objective was to study the short-term effects of Y. pseudotuberculosis on uptake of nanoparticles across human villus epithelium. Monolayers of human colon epithelium-derived Caco-2 cells and biopsies of normal human ileum were studied after 2 h exposure to Y. pseudotuberculosis expressing (inv+) or lacking (inv-) the bacterial adhesion molecule, invasin. Transepithelial transport of fluorescent nanoparticles (markers of transcytosis) was quantified by flow cytometry, and mechanisms explored by using inhibitors of endocytosis. Epithelial expressions of beta 1-integrin and particle uptake pathways were studied by confocal microscopy. The paracellular pathway was assessed by electrical resistance (TER), mannitol flux, and expression of tight junction proteins occludin and caludin-4 by confocal microscopy. Inv + Y. pseudotuberculosis adhered to the apical surface of epithelial cells and induced transcytosis of exogenous nanoparticles across Caco-2 monolayers (30-fold increase, P < 0.01) and ileal mucosa (268 +/- 47% of control; P < 0.01), whereas inv-bacteria had no effect on transcytosis. The transcytosis was concentration-, particle size-and temperature-dependent, and possibly mediated via macropinocytosis. Y. pseudotuberculosis also induced apical expression of beta 1-integrin on epithelial cells. A slight drop in TER was seen after exposure to inv+ Y. pseudotuberculosis, whereas mannitol flux and tight junction protein expression was unchanged. In summary, Y. pseudotuberculosis induced apical expression of beta 1-integrin and stimulated uptake of nanoparticles via invasin-dependent transcytosis in human intestinal epithelium. Our findings suggest that bacterial factors may initiate transcytosis of luminal exogenous particles across human ileal mucosa, thus presenting a novel mechanism of intestinal barrier dysfunction.

Keywords
barrier function, beta 1-integrin, Caco-2 cells, confocal microscopy, Crohns disease, Ussing chambers
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16079 (URN)10.1038/labinvest.2008.86 (DOI)
Available from: 2009-01-07 Created: 2009-01-07 Last updated: 2017-12-14Bibliographically approved
Sjöwall, J., Carlsson, A., Vaarala, O., Bergstrom, S., Ernerudh, J., Forsberg, P. & Ekerfelt, C. (2005). Innate immune responses in Lyme borreliosis: Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes. Clinical and Experimental Immunology, 141(1), 89-98
Open this publication in new window or tab >>Innate immune responses in Lyme borreliosis: Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes
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2005 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 141, no 1, p. 89-98Article in journal (Refereed) Published
Abstract [en]

Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, Interferon (INF)-? and tumour necrosis factor (TNF)-a in DCs and IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1a, MIP-1ß and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-a-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease. © 2005 British Society for Immunology.

Keywords
Borrelia, Clinical outcome, Dendritic cell, IL-12p70, TNF-a
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-50469 (URN)10.1111/j.1365-2249.2005.02820.x (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
Persborn, M., Wallon, C., Carlsson, A., Timmerman, H. & Söderholm, J. D.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
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(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
Schoultz, I., Carlsson, A., Gullberg, E., Almer, S., Ström, M., Lerm, M., . . . Söderholm, J. D.Infliximab reduces bacterial uptake in mucosal biopsies of Crohn’s colitis viamicrotubule-dependent pathway.
Open this publication in new window or tab >>Infliximab reduces bacterial uptake in mucosal biopsies of Crohn’s colitis viamicrotubule-dependent pathway
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: A defective intestinal barrier, shown by increased paracellular permeability is an importantpathogenic factor in Crohn’s disease (CD). TNFα is a key mediator in the regulation of the intestinal barrierfunction. Treatment with antibodies directed against TNFα, such as infliximab, has been established as animportant part of the therapeutic arsenal in severe Crohn’s disease, but the mechanisms of action have yet tobe elucidated. Part of infliximab’s effect has been suggested to be reduced apoptosis of epithelial cells andthereby reduced paracellular permeability. Our aim was to study how infliximab affects uptake of adherent E.coli across the colonic mucosa in CD.

Method: Seven patients with active CD colitis were examined before and after a four week treatment withinfliximab. Control biopsies were taken from healthy volunteers (4) and patients undergoing controlexamination for colonic polyps (4), aged 36 (range 25-81), coloscopy. Biopsies were taken from macroscopicallynon-inflamed descending colon and were mounted in Ussing chambers to study barrier function. Transmucosalpassage of green fluorescent protein (GFP) incorporated E. coli HM427, an adherent bacteria isolated from thecolon of a CD patient, was studied by quantifying the translocated fluorescent bacteria using flow cytometry.

Results: Bacterial passage across the colonic mucosa was increased in CD (2500 ± 300 arb. units) comparedwith controls (960 ± 280; p<0.05), and was reduced to 500 ± 200 units after the infliximab treatment (p<0.05).In biopsies treated with colchicine (a microtubuline inhibitor) uptake of E. coli HM427 was reduced by 2/3compared to non-treated biopsies.

Conclusion: Patients with active Crohn’s disease showed a defect in the barrier to adherent E. coli, which waspartly mediated through a microtubule dependent uptake. The four week treatment with infliximab improvedthe intestinal barrier to these bacteria. This may constitute an important part of infliximab’s mechanisms ofaction in active colitis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21097 (URN)
Available from: 2009-09-29 Created: 2009-09-29 Last updated: 2010-01-14Bibliographically approved
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