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The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation
  1. Sahar El Aidy1,2,
  2. Claire A Merrifield3,
  3. Muriel Derrien1,2,
  4. Peter van Baarlen4,
  5. Guido Hooiveld5,
  6. Florence Levenez6,
  7. Joel Doré6,
  8. Jan Dekker1,7,
  9. Elaine Holmes3,
  10. Sandrine P Claus8,
  11. Dirk-Jan Reijngoud9,
  12. Michiel Kleerebezem1,2,4,10
  1. 1Top Institute Food and Nutrition, Wageningen, The Netherlands
  2. 2Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
  3. 3Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
  4. 4Host-Microbe Interactomics, Wageningen University, Wageningen, The Netherlands
  5. 5Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
  6. 6INRA, UMR1319, Jouy-en-Josas, France
  7. 7Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands
  8. 8Department of Food and Nutritional Sciences, The University of Reading, Reading, UK
  9. 9Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  10. 10Department of Health, NIZO food research, Ede, The Netherlands
  1. Correspondence to Michiel Kleerebezem, Health Department, NIZO food research, PO Box 20, Ede 6710 BA, The Netherlands; michiel.kleerebezem{at}


Objective Proper interactions between the intestinal mucosa, gut microbiota and nutrient flow are required to establish homoeostasis of the host. Since the proximal part of the small intestine is the first region where these interactions occur, and since most of the nutrient absorption occurs in the jejunum, it is important to understand the dynamics of metabolic responses of the mucosa in this intestinal region.

Design Germ-free mice aged 8–10 weeks were conventionalised with faecal microbiota, and responses of the jejunal mucosa to bacterial colonisation were followed over a 30-day time course. Combined transcriptome, histology, 1H NMR metabonomics and microbiota phylogenetic profiling analyses were used.

Results The jejunal mucosa showed a two-phase response to the colonising microbiota. The acute-phase response, which had already started 1 day after conventionalisation, involved repression of the cell cycle and parts of the basal metabolism. The secondary-phase response, which was consolidated during conventionalisation (days 4–30), was characterised by a metabolic shift from an oxidative energy supply to anabolic metabolism, as inferred from the tissue transcriptome and metabonome changes. Detailed transcriptome analysis identified tissue transcriptional signatures for the dynamic control of the metabolic reorientation in the jejunum. The molecular components identified in the response signatures have known roles in human metabolic disorders, including insulin sensitivity and type 2 diabetes mellitus.

Conclusion This study elucidates the dynamic jejunal response to the microbiota and supports a prominent role for the jejunum in metabolic control, including glucose and energy homoeostasis. The molecular signatures of this process may help to find risk markers in the declining insulin sensitivity seen in human type 2 diabetes mellitus, for instance.

  • C57/BL 6J ex-germ-free mice
  • jejunum
  • transcriptome
  • metabonome
  • microbiota
  • gut immunology
  • gastrointestinal tract
  • gene expression
  • gene regulation
  • gut inflammation
  • probiotics
  • mucosal immunology
  • mucins
  • anti-bacterial mucosal immunity
  • bacterial interactions
  • Campylobacter jejuni
  • colonic microflora
  • crohn's disease
  • intestinal bacteria
  • immune response
  • energy metabolism
  • liver metabolism
  • glucose metabolism
  • lipid metabolism
  • inherited metabolic disease

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  • Funding This work was funded by the Top Institute Food and Nutrition (TIFN, Wageningen).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.