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

S. El Aidy, C.A. Merrifield, M. Derrien, P. van Baarlen, G.J. Hooiveld, F. Levenez, J. Dore, J. Dekker, E. Holmes, S.P. Claus, D.J. Reijngoud, M. Kleerebezem

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Abstract

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, (1)H 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.
Original languageEnglish
Pages (from-to)1306-1314
JournalGut
Volume62
DOIs
Publication statusPublished - 2013

Fingerprint

Microbiota
Mucous Membrane
Jejunum
Intestinal Mucosa
Transcriptome
Type 2 Diabetes Mellitus
Insulin Resistance
Homeostasis
Basal Metabolism
Food
Acute-Phase Reaction
Metabolomics
Gene Expression Profiling
Small Intestine
Histology
Cell Cycle
Glucose
Gastrointestinal Microbiome

Keywords

  • inflammatory-bowel-disease
  • gastric bypass
  • amino-acid
  • glutamate
  • intestine
  • surgery
  • mice
  • biosynthesis
  • homeostasis
  • expression

Cite this

El Aidy, S. ; Merrifield, C.A. ; Derrien, M. ; van Baarlen, P. ; Hooiveld, G.J. ; Levenez, F. ; Dore, J. ; Dekker, J. ; Holmes, E. ; Claus, S.P. ; Reijngoud, D.J. ; Kleerebezem, M. / The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation. In: Gut. 2013 ; Vol. 62. pp. 1306-1314.
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title = "The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation",
abstract = "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, (1)H 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.",
keywords = "inflammatory-bowel-disease, gastric bypass, amino-acid, glutamate, intestine, surgery, mice, biosynthesis, homeostasis, expression",
author = "{El Aidy}, S. and C.A. Merrifield and M. Derrien and {van Baarlen}, P. and G.J. Hooiveld and F. Levenez and J. Dore and J. Dekker and E. Holmes and S.P. Claus and D.J. Reijngoud and M. Kleerebezem",
year = "2013",
doi = "10.1136/gutjnl-2011-301955",
language = "English",
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El Aidy, S, Merrifield, CA, Derrien, M, van Baarlen, P, Hooiveld, GJ, Levenez, F, Dore, J, Dekker, J, Holmes, E, Claus, SP, Reijngoud, DJ & Kleerebezem, M 2013, 'The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation', Gut, vol. 62, pp. 1306-1314. https://doi.org/10.1136/gutjnl-2011-301955

The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation. / El Aidy, S.; Merrifield, C.A.; Derrien, M.; van Baarlen, P.; Hooiveld, G.J.; Levenez, F.; Dore, J.; Dekker, J.; Holmes, E.; Claus, S.P.; Reijngoud, D.J.; Kleerebezem, M.

In: Gut, Vol. 62, 2013, p. 1306-1314.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation

AU - El Aidy, S.

AU - Merrifield, C.A.

AU - Derrien, M.

AU - van Baarlen, P.

AU - Hooiveld, G.J.

AU - Levenez, F.

AU - Dore, J.

AU - Dekker, J.

AU - Holmes, E.

AU - Claus, S.P.

AU - Reijngoud, D.J.

AU - Kleerebezem, M.

PY - 2013

Y1 - 2013

N2 - 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, (1)H 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.

AB - 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, (1)H 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.

KW - inflammatory-bowel-disease

KW - gastric bypass

KW - amino-acid

KW - glutamate

KW - intestine

KW - surgery

KW - mice

KW - biosynthesis

KW - homeostasis

KW - expression

U2 - 10.1136/gutjnl-2011-301955

DO - 10.1136/gutjnl-2011-301955

M3 - Article

VL - 62

SP - 1306

EP - 1314

JO - Gut

JF - Gut

SN - 0017-5749

ER -