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Infection and Immunity, June 2005, p. 3686-3692, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3686-3692.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Strain-Specific Effects of Probiotics on Gut Barrier Integrity following Hemorrhagic Shock

Misha D. Luyer,1 Wim A. Buurman,1* M'hamed Hadfoune,1 Gea Speelmans,3 Jan Knol,3 Jan A. Jacobs,2 Cornelis H. C. Dejong,1 Aldwin J. M. Vriesema,3 and Jan Willem M. Greve1

Department of Surgery,1 Department of Medical Microbiology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), University of Maastricht and University Hospital, Maastricht, The Netherlands,2 Department of Biomedical Research, Section Microbiology, Numico Research B.V., Wageningen, The Netherlands3

Received 30 November 2004/ Returned for modification 11 January 2005/ Accepted 2 February 2005

Probiotic therapy modulates the composition of the intestinal flora and inhibits the inflammatory response. These properties may be of benefit in the preservation of gut barrier integrity after injury or stress. In this study, we examined the effect of two Lactobacillus strains selected for their pathogen exclusion properties on intestinal barrier integrity following hemorrhagic shock. Additionally, the responsiveness of the macrophage cell line RAW 264.7 to combined exposure to Lactobacillus DNA or oligodeoxynucleotides containing CpG motifs (CpG-ODN) and endotoxin was assessed by measuring tumor necrosis factor alpha (TNF-{alpha}) release. Rats were administered lactobacilli (5 x 109 CFU) or vehicle for 7 days and were subjected subsequently to hemorrhagic shock by withdrawal of 2.1 ml blood/100 g tissue. Levels of plasma endotoxin, bacterial translocation to distant organs, and filamentous actin (F-actin) in the ileum were determined 24 h later. Rats treated with Lactobacillus rhamnosus showed reduced levels of plasma endotoxin (8 ± 2 pg/ml versus 24 ± 4 pg/ml; P = 0.01), bacterial translocation (2 CFU/gram versus 369 CFU/gram; P < 0.01), and disruption of F-actin distribution following hemorrhagic shock compared with nontreated control rats. In contrast, pretreatment with Lactobacillus fermentum had no substantial effect on gut barrier integrity. Interestingly, DNA preparations from both lactobacilli reduced endotoxin-induced TNF-{alpha} release dose dependently, whereas CpG-ODN increased TNF-{alpha} release. In conclusion, the pathogen exclusion properties of both Lactobacillus strains and the reduction of endotoxin-induced inflammation by their DNA in vitro are not prerequisites for a beneficial effect of probiotic therapy on gut barrier function following hemorrhagic shock. Although pretreatment with Lactobacillus spp. may be useful to preserve gut barrier integrity following severe hypotension, a thorough assessment of specific strains seems to be essential.

* Corresponding author. Mailing address: Department of Surgery, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Phone: 31 43 3881499. Fax: 31 43 3884154. E-mail: W.Buurman{at}ah.unimaas.nl.

Editor: F. C. Fang

Infection and Immunity, June 2005, p. 3686-3692, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3686-3692.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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