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

Gut. 2012 Jun;61(6):829-38. doi: 10.1136/gutjnl-2011-300367. Epub 2011 Oct 24.

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 5×10⁷ 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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cyclooxygenase 2 / physiology*
  • Female
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / radiation effects*
  • Lacticaseibacillus rhamnosus / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / physiology
  • Probiotics / therapeutic use*
  • Radiation Injuries, Experimental / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 2 / physiology*
  • Whole-Body Irradiation / adverse effects*

Substances

  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2