Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species

EMBO J. 2013 Nov 27;32(23):3017-28. doi: 10.1038/emboj.2013.224. Epub 2013 Oct 18.

Abstract

The resident prokaryotic microbiota of the metazoan gut elicits profound effects on the growth and development of the intestine. However, the molecular mechanisms of symbiotic prokaryotic-eukaryotic cross-talk in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signalling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. Here, we report that commensal bacteria, particularly members of the genus Lactobacillus, can stimulate NADPH oxidase 1 (Nox1)-dependent ROS generation and consequent cellular proliferation in intestinal stem cells upon initial ingestion into the murine or Drosophila intestine. Our data identify and highlight a highly conserved mechanism that symbiotic microorganisms utilize in eukaryotic growth and development. Additionally, the work suggests that specific redox-mediated functions may be assigned to specific bacterial taxa and may contribute to the identification of microbes with probiotic potential.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation*
  • Drosophila / growth & development
  • Drosophila / metabolism
  • Drosophila / microbiology*
  • Histones / metabolism
  • Host-Pathogen Interactions
  • Intestinal Mucosa / metabolism
  • Intestines / cytology*
  • Intestines / microbiology
  • Lactobacillus / pathogenicity
  • Larva / cytology*
  • Larva / metabolism
  • Larva / microbiology
  • Mice
  • NADH, NADPH Oxidoreductases / metabolism*
  • NADPH Oxidase 1
  • Oxidation-Reduction
  • Phosphorylation
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Stem Cells / microbiology
  • Symbiosis

Substances

  • Histones
  • Reactive Oxygen Species
  • NADH, NADPH Oxidoreductases
  • NADPH Oxidase 1
  • NOX1 protein, mouse