Effects of feeding lactobacillus GG on lethal irradiation in mice.
ABSTRACT Mice exposed to 1400 rads of total body irradiation experienced 80%-100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative bacteremia in these animals compared with controls.
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ABSTRACT: The small intestinal epithelium is highly sensitive to radiation and is a major site of injury during radiation therapy and environmental overexposure. To examine probiotic bacteria as potential radioprotective agents in the intestine. 8-week-old C57BL/6 wild-type or knockout mice were administered probiotic by gavage for 3 days before 12 Gy whole body radiation. The intestine was evaluated for cell-positional apoptosis (6 h) and crypt survival (84 h). Gavage of 5×10⁷ Lactobacillus rhamnosus GG (LGG) improved crypt survival about twofold (p<0.01); the effect was observed when administered before, but not after, radiation. Conditioned medium (CM) from LGG improved crypt survival (1.95-fold, p<0.01), and both LGG and LGG-CM reduced epithelial apoptosis particularly at the crypt base (33% to 18%, p<0.01). LGG was detected in the distal ileal contents after the gavage cycle, but did not lead to a detectable shift in bacterial family composition. The reduction in epithelial apoptosis and improved crypt survival offered by LGG was lost in MyD88⁻/⁻, TLR-2⁻/⁻ and cyclo-oxygenase-2⁻/⁻ (COX-2) mice but not TLR-4⁻/⁻ mice. LGG administration did not lead to increased jejunal COX-2 mRNA or prostaglandin E2 levels or a change in number of COX-2-expressing cells. However, a location shift was observed in constitutively COX-2-expressing cells of the lamina propria from the villi to a position near the crypt base (villi to crypt ratio 80:20 for control and 62:38 for LGG; p<0.001). Co-staining revealed these COX-2-expressing small intestinal lamina propria cells to be mesenchymal stem cells. LGG or its CM reduce radiation-induced epithelial injury and improve crypt survival. A TLR-2/MyD88 signalling mechanism leading to repositioning of constitutive COX-2-expressing mesenchymal stem cells to the crypt base is invoked.Gut 10/2011; 61(6):829-38. · 10.73 Impact Factor
- 11/2010: pages 1 - 16; , ISBN: 9781444329384
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ABSTRACT: Intestinal injury from ionizing radiation is a clinically important entity, as enteritis symptoms occur commonly after radiotherapy for pelvic malignancies. Preventative or therapeutic options for radiation enteritis are mostly unsatisfactory; however, available data suggests that probiotic bacteria--those which confer health benefit--may have therapeutic value. Previous reports from both human trials and animal models have evaluated various end points for probiotic usage in limiting radiation-associated intestinal damage. Newer data suggests that particular probiotics and/or their secreted or derived bacterial products may have unique radioprotective properties. We will review the area with a focus on new developments surrounding probiotic therapy in radiation-induced intestinal injury and repair.Annals of the New York Academy of Sciences 06/2009; 1165:190-4. · 4.38 Impact Factor