Pre-treatment with probiotics prolongs survival after experimental infection by multidrug-resistant Pseudomonas aeruginosa in rodents: An effect on sepsis-induced immunosuppression
Introduction
Hospital-acquired infections remain the most important complications of patients hospitalised in intensive care units (ICUs). Several double-blind randomised trials have been published throughout the last years indicating that oral administration of probiotics can decrease the incidence of these infections [1], [2], [3], [4], [5], [6], [7], [8]. Despite their clinical benefit, the mechanism of action of probiotics has not been analysed in these studies. Moreover, most of these studies are characterised by great heterogeneity due to the different species of probiotics administered to patients. It appears that the benefit from probiotics depends greatly on the type of administered probiotic. Some studies have used preparations of single probiotic species and others have used a mixture of probiotics.
Probiotics are living micro-organisms widely found in nutritional supplements. With regard to their mechanisms of action, they are thought to act either by modulation of the intestinal microecology so as to prevent bacterial translocation into the systemic circulation or by modifying the immune response of the host [9].
The current study goes well beyond previously published animal models and aims to provide clear-cut answers on the mechanism of prevention of severe infections by multidrug-resistant (MDR) Pseudomonas aeruginosa following pre-treatment with probiotics. MDR P. aeruginosa is a common pathogen in patients hospitalised in the ICU. This study also aimed to challenge the findings of previous randomised clinical trials, some testing one single probiotic species and others testing a mixture of probiotics. To this end, the study was conducted in two steps: a first step evaluating the efficacy of pre-treatment with Lactobacillus plantarum, which was contained in all probiotic preparations administered in randomised trials of critically ill patients [1], [2], [3], [4], [5], [6], [7], [8]; and a second step evaluating the effect of a commercially available preparation of four probiotics.
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Experimental animals
A total of 309 male C57BL/6 outbred mice weighing 20–25 g and aged 7–9 weeks (Hellenic Pasteur Institute, Athens, Greece) were used. Experiments were performed in the Laboratory for Experimental Medicine of ATTIKON University General Hospital (Athens, Greece). Following acclimatisation, mice were kept in metal cages with a constant rotation rate of 70 air-changes per hour. Mice were fed standard chow (type 4rf 18) and were allowed water ad libitum. Mice were kept in an isolated room with a
Results
In the first set of experiments, an important protective effect of pre-treatment with L. plantarum in experimental sepsis induced by MDR P. aeruginosa was found. Survival was 90% for group A, 31.3% for group B and 66.7% for group C (Fig. 1A). A similar protective effect from L. plantarum pre-treatment was found against experimental sepsis by E. coli (Fig. 1B). Survival was 12.0% for group D and 56.0% for group E. This survival benefit was not connected to any change in growth of inoculated
Discussion
The current study suggests a major prophylactic effect of probiotics either as a single species or as combination of four species against experimental sepsis by MDR P. aeruginosa. The results showed that the action of probiotics is mediated through modulation of the immune function of the host. Current knowledge suggests that when severe sepsis or septic shock develops, the host is entering into a state of immunoparalysis where circulating monocytes are exhausted for the production of
Funding
This study was funded in part by a grant from Smart Intermed (Athens, Greece) to the University of Athens (Athens, Greece) [grant 70/3/9605]. LactoLevure® powder was a kind donation from Uni-Pharma (Athens, Greece).
Competing interests
None declared.
Ethical approval
This study was approved by the Veterinary Directorate of the Prefecture of Athens, Greece [license 7438/13.12.2012].
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