Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner

Matthew A. Ciorba, Terrence E. Riehl, M. Suprada Rao, Clara Moon, Xueping Ee, Gerardo M. Nava, Monica R. Walker, Jeffrey M. Marinshaw, Thaddeus S. Stappenbeck, William F. Stenson

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Background: The small intestinal epithelium is highly sensitive to radiation and is a major site of injury during radiation therapy and environmental overexposure. Objective: To examine probiotic bacteria as potential radioprotective agents in the intestine. Methods: 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). Results: Gavage of 5×10 7 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalGut
Volume61
Issue number6
DOIs
StatePublished - Jun 1 2012

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    Ciorba, M. A., Riehl, T. E., Rao, M. S., Moon, C., Ee, X., Nava, G. M., Walker, M. R., Marinshaw, J. M., Stappenbeck, T. S., & Stenson, W. F. (2012). Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner. Gut, 61(6), 829-838. https://doi.org/10.1136/gutjnl-2011-300367