title: Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia.
abstract: OBJECTIVE
  To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk.
  
  
  METHODS
  We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease.
  
  
  RESULTS
  Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD.
  
  
  CONCLUSIONS
  Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Pomié
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Blasco-Baque
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Klopp
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Nicolas
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Waget
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Loubières
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Azalbert
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Puel
authors.affiliation: Groupe Protéomique Centre Recherche Cancer Toulouse, Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1037, 2 avenue Hubert Curien, CS 53717, 31037 Toulouse Cedex 1, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lopez
authors.affiliation: Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 3: « Adipokines, obesity and associated Pathologies », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Dray
authors.affiliation: Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 3: « Adipokines, obesity and associated Pathologies », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: VAIOMER SAS, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lelouvier
authors.affiliation: VAIOMER SAS, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Servant
authors.affiliation: VAIOMER SAS, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Courtney
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Amar
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France. Electronic address: remy.burcelin@inserm.fr.
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France. Electronic address: lucile.garidou@gmail.com.
authors.forename: Lucile
authors.initials: L
authors.lastname: Garidou
keywords: APC, Antigen presenting cells; AT, Adipose tissue; Gut microbiota and metabolic diseases; Immunity; Insulin resistance; LN, Lymph nodes; NC, Normal chow; T2D, Type 2 diabetes; VL, Vastus lateralis muscle