PROBIOTIC BACTERIA MAINTAIN COLONIC PERMEABILITY AND REDUCE PRO-INFLAMMATORY CYTOKINE RELEASE IN MODS

R Endersby, J Walker, H Jijon, J Backer, KL Madsen

University of Alberta, Edmonton, Alberta

Multiple organ dysfunction syndrome (MODS) is a major cause of death in patients in the intensive care unit. A breakdown in intestinal permeability leading to increases in bacterial translocation and release of pro-inflammatory cytokines is associated with the pathogenesis of MODS. The aim of the study was to determine if altering the bacterial composition of the gut with probiotic bacteria would reduce the intestinal permeability and cytokine secretion associated with MODS.
METHODS: Wild-type and IL-10 deficient 129 Sv/Ev mice were fed VSL#3 (2.8 x 10⁸ cfu/d) containing 4 strains of lactobacilli, 3 strains of bifidobacteria and 1 strain of Streptococcus salivarius subsp. thermophilus for 4 days. On the day of study, mice were injected ip with 40 mg/kg LPS combined with 360 mg/kg of D-galactosamine (GalN) to induce MODS. After 6 hrs, mice were sacrificed and colons removed for analysis of cytokine production and epithelial function. Tissue was mounted in Ussing Chambers for measurement of permeability as assessed by mannitol movement and cAMP-dependent chloride secretion in response to forskolin.
RESULTS: Wild-type mice (n=8) injected with LPS/GalN demonstrated a significant (p<0.05) increase in colonic mannitol flux (27.2±3.7 nm/cm²/hr) compared with untreated controls (10.5±1.0 nm/cm²/hr; n=7). Mice treated with LPS/GalN also showed a significant reduction in forskolin-stimulated chloride secretion and increased TNFa and IFNg secretion. Pre-treatment with VSL#3 attenuated the rise in mannitol flux (14.7±1.1 nm/cm²/hr), reduced TNFa and IFNg secretion, and maintained cAMP-dependent forskolin secretion. IL-10 deficient mice pre-treated with VSL#3 received similar protection against an LPS/GalN-induced increase in colonic permeability, suggesting that IL-10 is not required for the beneficial effect of probiotic bacteria in the maintenance of epithelial function.
CONCLUSIONS: In conclusion, altering the colonic microflora with probiotic bacteria is protective against the development of MODS, and may be a useful adjunctive therapy for at risk patients in the intensive care unit.