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Critical Care

Volume 18 Supplement 2

Sepsis 2014

Open Access

Probiotic pretreatment improves survival and prevents gut mucosal barrier dysfunction in sepsis

  • KL Calisto1,
  • ACAP Camacho1,
  • FC Mittestainer1,
  • MCS Mendes1,
  • AC Santos1 and
  • MJA Saad1
Critical Care201418(Suppl 2):P69

Published: 3 December 2014


Intestinal PermeabilityLactobacillus AcidophilusProbiotic TreatmentBifidobacterium LongumLactobacillus Bulgaricus


The gut is the largest immune organ and plays a central role in the promotion of systemic inflammatory responses [1]. Perturbations of intestinal epithelial homeostasis during sepsis include increased proinflammatory cytokine production, increased intestinal permeability and apoptosis [26]. Healthy gut is essential to promote host health and prevent organ dysfunction in sepsis. Probiotics seem to keep gut homeostasis through different pathways, such as the modulation of microbial activity, energy regulation, anti-inflammatory cytokine production, gene expression and cell differentiation [7]. Probiotics have been shown an effective treatment in various clinical conditions, although the potential benefits of probiotic treatment in sepsis remain largely undefined. The aim of the present study was to investigate the effect of probiotic treatment on gut dysfunction and inflammatory signaling in septic rats.


Sepsis was induced by cecal ligation and puncture (CLP) in Wistar male rats (8 weeks old). They were pretreated with probiotics or vehicle once a day during 7 days before CLP. The chosen probiotic mixture contained 10 × 107 CFU Bifidobacterium longum, 10 × 106 CFU Lactobacillus bulgaricus, 10 × 106 CFU Lactobacillus acidophilus. Colonic tissue and serum samples were collected 24 hours after CLP for ELISA and protein expression analysis by western blotting.


Our data demonstrate that probiotic pretreatment improved survival of septic rats (Figure 1) and this effect is accompanied by a marked decrease of IL-1β and TNFα (Figure 2A,B). Sepsis leads to severe intestinal epithelial damage with a decrease in claudin 2 and occludin protein expression (Figure 3A,B); probiotic pretreatment reversed these alterations in parallel with an increase in Hsp72 and Hsp25 activation (Figure 4A,B). In intestinal epithelial cells, the inducible Hsp have been shown to preserve tight junction and barrier function. The maintenance of epithelial barrier integrity induced by probiotic pretreatment, in parallel with an activation of cytoprotective pathway, may culminate in the restoration of the intestinal epithelial function.
Figure 1

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Figure 2

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Figure 3

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Figure 4

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Our results show that probiotics pretreatment fulfills a dual function at the intestinal mucosa: in addition to preventing intestinal permeability disruption, it also attenuates proinflammatory cytokine release, diminishing the exacerbate host's reaction to infection and offering a novel prophylactic strategy to sepsis.

Authors’ Affiliations

Department of Internal Medicine, UNICAMP Campinas, Brazil


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© Calisto et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.