The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation

Sahar El Aidy, Claire A. Merrifield, Muriel Derrien, Peter van Baarlen, Guido Hooiveld, Florence Levenez, Joel Dore, Jan Dekker, Elaine Holmes, Sandrine P. Claus, Dirk-Jan Reijngoud, Michiel Kleerebezem*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    92 Citations (Scopus)



    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.


    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, H-1 NMR metabonomics and microbiota phylogenetic profiling analyses were used.


    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.


    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.

    Original languageEnglish
    Pages (from-to)1306-1314
    Number of pages9
    Issue number9
    Publication statusPublished - Sep-2013


    • 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
    • MICE

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