Differential Modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids.

S. Lukovac, C. Belzer, L. Pellis, B.J. Keijser, W.M. de Vos, R.C. Montijn, G. Roeselers

Research output: Contribution to journalArticleAcademicpeer-review

148 Citations (Scopus)

Abstract

The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional response of organoids upon exposure to short-chain fatty acids (SCFAs) and products generated by two abundant microbiota constituents, Akkermansia muciniphila and Faecalibacterium prausnitzii. We observed that A. muciniphila metabolites affect various transcription factors and genes involved in cellular lipid metabolism and growth, supporting previous in vivo findings. Contrastingly, F. prausnitzii products exerted only weak effects on host transcription. Additionally, A. muciniphila and its metabolite propionate modulated expression of Fiaf, Gpr43, histone deacetylases (HDACs), and peroxisome proliferator-activated receptor gamma (Ppar¿), important regulators of transcription factor regulation, cell cycle control, lipolysis, and satiety. This work illustrates that specific bacteria and their metabolites differentially modulate epithelial transcription in mouse organoids. We demonstrate that intestinal organoids provide a novel and powerful ex vivo model for host-microbiome interaction studies.
Original languageEnglish
Article numbere01438-14
Number of pages10
JournalmBio
Volume5
Issue number4
DOIs
Publication statusPublished - 2014

Keywords

  • chain fatty-acids
  • diet-induced obesity
  • intestinal microbiota
  • cholesterol-synthesis
  • adipose factor
  • gen. nov.
  • in-vitro
  • colon
  • cell
  • expression

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