Abstract
The gastrointestinal tract harbours a huge load of bacteria which exerts important biological functions to maintain health. In certain conditions the relation between commensal bacteria and pathogens may be set off balance, with an increase in number of pathogens and risk of bacterial translocation (BT). Disease and trauma may also render the intestinal barrier dysfunctional, inducing BT and increased permeability. Probiotic bacteria, i.e. living bacteria which, when ingested, exerts beneficial effects on the host, have been found to stabilize the intestinal mucosa and affect the intestinal microflora. The aim of this thesis was to study the effects of Lactobacillus plantarum 299v in relation to intestinal permeability and BT.
In study I L. plantarum 299v normalized E. coli-induced permeability in distal ileum of rats. This effect was achieved with a more continuous supply of L. plantarum 299v, rather than intermittent or acute pretreatment.
Study II showed that pretreatment with L. plantarum 299v prevented BT in rats rendered septic with LPS. The protective effect seemed to be dependent on the ability of L. plantarum 299v to adhere to intestinal mucosa, indicating competitive inhibition as a possible mechanism behind prevention of translocation. Moreover, treatment with prebiotics, without a probioticum, did not prevent translocation.
In study III LPS-induced intestinal barrier dysfunction on rats was found to be regulated by P-selectin-dependent leukocyte recruitment. With anti-P-selectin antibody intestinal permeability was attenuated, as well as leukocyte rolling and adhesion. This indicates anti-P-selectin treatment as a mean of ameliorating barrier dysfunction in sepsis.
Finally, in study IV, it was found that high doses of L. plantarum 299v given to patients undergoing colon surgery were not able to reduce translocation of selected enteric bacteria but seemed to have a stimulatory effect on bacterial load in the colon. Further, L. plantarum 299v could be given to patients with malignancy without risk of tumour proliferation.
Taken together, the findings herein indicates a potential of L. plantarum 299v pretreatment in reducing BT and intestinal permeability and warrants further studies in the clinical setting.
In study I L. plantarum 299v normalized E. coli-induced permeability in distal ileum of rats. This effect was achieved with a more continuous supply of L. plantarum 299v, rather than intermittent or acute pretreatment.
Study II showed that pretreatment with L. plantarum 299v prevented BT in rats rendered septic with LPS. The protective effect seemed to be dependent on the ability of L. plantarum 299v to adhere to intestinal mucosa, indicating competitive inhibition as a possible mechanism behind prevention of translocation. Moreover, treatment with prebiotics, without a probioticum, did not prevent translocation.
In study III LPS-induced intestinal barrier dysfunction on rats was found to be regulated by P-selectin-dependent leukocyte recruitment. With anti-P-selectin antibody intestinal permeability was attenuated, as well as leukocyte rolling and adhesion. This indicates anti-P-selectin treatment as a mean of ameliorating barrier dysfunction in sepsis.
Finally, in study IV, it was found that high doses of L. plantarum 299v given to patients undergoing colon surgery were not able to reduce translocation of selected enteric bacteria but seemed to have a stimulatory effect on bacterial load in the colon. Further, L. plantarum 299v could be given to patients with malignancy without risk of tumour proliferation.
Taken together, the findings herein indicates a potential of L. plantarum 299v pretreatment in reducing BT and intestinal permeability and warrants further studies in the clinical setting.
Original language | English |
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Qualification | Doctor |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 2007 Feb 8 |
Publisher | |
ISBN (Print) | 91-85559-85-7 |
Publication status | Published - 2007 |
Bibliographical note
Defence detailsDate: 2007-02-08
Time: 09:00
Place: Lecture hall, Dept of Surgery, Malmö University Hospital, entrance 42
External reviewer(s)
Name: Söderholm, Johan
Title: Associate professor
Affiliation: Dept or Surgery, University of Linköping
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<div class="article_info">P Mangell, P Nejdfors, M Wang, S Ahrné, B Weström, H Thorlacius and B Jeppsson. <span class="article_issue_date">2002</span>. <a href="javascript:downloadFile(547952)" class="article_link">Lactobacillus plantarum 299v Inhibits Escherichia coli-Induced Intestinal Permeability.</a> <span class="journal_series_title">Dig Dis Sci</span>, <span class="journal_volume">vol 47</span> <span class="journal_pages">pp 511-16</span>.</div>
<div class="article_info">P Mangell, P Lennernäs, M Wang, C Olsson, S Ahrné, G Molin, H Thorlacius and B Jeppsson. <span class="article_issue_date">2006</span>. <a href="javascript:downloadFile(547953)" class="article_link">Adhesive Capability of Lactobacillus plantarum 299v is Important for Preventing Bacterial Translocation in Endotoxaemic Rats.</a> <span class="journal_series_title">APMIS</span>, <span class="journal_volume">vol 114</span> <span class="journal_pages">pp 611-8</span>.</div>
<div class="article_info">P Mangell, A Mihaescu, Y Wang, R Schramm, B Jeppsson and H Thorlacius. <span class="article_issue_date">2006</span>. <a href="javascript:downloadFile(547954)" class="article_link">Critical Role of P-selectin-dependent Leukocyte Recruitment in Endotoxin-induced Intestinal Barrier Dysfunction in Mice.</a> <span class="journal_series_title">Infl Res</span>, (accepted)</div>
<div class="article_info">P Mangell, H Thorlacius, I Syk, S Ahrné, G Molin, C Olsson and B Jeppsson. <span class="article_issue_date"></span>. <span class="article_title">L. plantarum 299v to Patients Undergoing Colon Resection – A Randomised Placebo-controlled Study.</span> (manuscript)</div>
Subject classification (UKÄ)
- Surgery
Free keywords
- bacterial translocation
- permeability
- intestinal microflora
- Kirurgi
- orthopaedics
- P-selectin
- ortopedi
- traumatologi
- leukocyte recruitment
- Lactobacillus plantarum 299v
- traumatology
- Surgery
- colon resection