Non-pathogenic bacteria modulate colonic epithelial gene expression in germ-free mice

Kouhei Fukushima, H. Ogawa, K. Takahashi, H. Naito, Y. Funayama, T. Kitayama, H. Yonezawa, I. Sasaki

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Background: We established a bacterial reconstitution model to investigate epithelial cell-luminal bacteria interaction. The aim of the study was to identify the known genes directly or indirectly modulated by non-pathologic bacterial flora in the colonic epithelia of germ-free mice. Methods: Germ-free mice were orally given a bacterial suspension prepared from specific pathogen-free counterparts (bacterial reconstitution). Colonic epithelial cells were isolated, then total and poly (A) RNA were extracted. We investigated differential gene expression in colonic epithelial cells among germ-free, bacteria-reconstituted, and specific pathogen-free mice by DNA microarray. Finally, differential expression was confirmed by Northern blot or quantitative RT-PCR. Results: Thirty genes were initially selected as differentially expressed genes in DNA microarray analysis. We confirmed that genes associated with growth (Reg IIIβ, Reg IIIγ, guanylate nucleotide binding protein 2), apoptosis (Bcl-associated death promotor), cytoskeleton (tubulin α4, erythrocyte protein band 7.2), and immune response (lymphocyte antigen complex 6) were induced by bacterial reconstitution. In contrast, genes possibly participating in extracellular oxidant defence (selenoprotein P, metallothionein 1) and cellular metabolism (cytochrome P450, HMGCoA synthase 2, alcohol dehydrogenase 1 complex, aldehyde dehydrogenase family 1, carbonic anhydrase 1, glycoprotein galactosyltransferase α1,3) were down-regulated by bacterial challenge. Conclusion: Non-pathogenic bacteria modulated colonic gene expression in germ-free mice, suggesting that non-pathogenic bacteria possibly initiate epithelial change in genetically normal and/or abnormal hosts. The present study provides a basis for the functional study of each molecule in symbiosis with luminal bacteria in healthy and diseased colon.

Original languageEnglish
Pages (from-to)626-634
Number of pages9
JournalScandinavian journal of gastroenterology
Issue number6
Publication statusPublished - 2003 Jun 1
Externally publishedYes


  • Bacterial reconstitution
  • Epithelial cells
  • Gene expression
  • Germ-free
  • Microarray

ASJC Scopus subject areas

  • Gastroenterology


Dive into the research topics of 'Non-pathogenic bacteria modulate colonic epithelial gene expression in germ-free mice'. Together they form a unique fingerprint.

Cite this