title: Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism.
abstract: Gut microbiota dysbiosis has been implicated in a variety of systemic disorders, notably metabolic diseases including obesity and impaired liver function, but the underlying mechanisms are uncertain. To investigate this question, we transferred caecal microbiota from either obese or lean mice to antibiotic-free, conventional wild-type mice. We found that transferring obese-mouse gut microbiota to mice on normal chow (NC) acutely reduces markers of hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non-inoculated mice, a phenotypic trait blunted in conventional NOD2 KO mice. Furthermore, transferring of obese-mouse microbiota changes both the gut microbiota and the microbiome of recipient mice. We also found that transferring obese gut microbiota to NC-fed mice then fed with a high-fat diet (HFD) acutely impacts hepatic metabolism and prevents HFD-increased hepatic gluconeogenesis compared to non-inoculated mice. Moreover, the recipient mice exhibit reduced hepatic PEPCK and G6Pase activity, fed glycaemia and adiposity. Conversely, transfer of lean-mouse microbiota does not affect markers of hepatic gluconeogenesis. Our findings provide a new perspective on gut microbiota dysbiosis, potentially useful to better understand the aetiology of metabolic diseases.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), 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.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse Cedex 4, France.|Faculté de Chirurgie Dentaire de Toulouse, Université Paul Sabatier, Toulouse Cedex, France.
authors.forename: Vincent
authors.identifier: 0000-0003-3012-8980
authors.initials: V
authors.lastname: Blasco-Baque
authors.affiliation: Toulouse III, Institut de Recherche en Santé Digestive (IRSD) Team 3, "Intestinal Neuroimmune Interactions" INSERM U1220, Université Paul Sabatier, Toulouse Cedex 3, France.|European Associated Laboratory NeuroMicrobiota (INSERM/UCL), Bâtiment B - Pavillon Lefebvre, Toulouse Cedex 3, France.
authors.forename: Audren
authors.initials: A
authors.lastname: Fournel
authors.affiliation: INSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'Azur, Nice, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Gilleron
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), 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.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse Cedex 4, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Waget
authors.affiliation: INSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'Azur, Nice, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Ceppo
authors.affiliation: Toulouse III, Institut de Recherche en Santé Digestive (IRSD) Team 3, "Intestinal Neuroimmune Interactions" INSERM U1220, Université Paul Sabatier, Toulouse Cedex 3, France.|European Associated Laboratory NeuroMicrobiota (INSERM/UCL), Bâtiment B - Pavillon Lefebvre, Toulouse Cedex 3, France.
authors.forename: Alysson
authors.initials: A
authors.lastname: Marlin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse Cedex 4, France.
authors.forename: Roshan
authors.identifier: 0000-0001-6781-8569
authors.initials: R
authors.lastname: Padmanabhan
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse Cedex 4, France.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse Cedex 4, France.
authors.forename: François
authors.initials: F
authors.lastname: Tercé
authors.affiliation: Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Patrice D
authors.identifier: 0000-0003-2040-2448
authors.initials: PD
authors.lastname: Cani
authors.affiliation: INSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'Azur, Nice, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanti
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse Cedex 4, France.
authors.forename: Remy
authors.initials: R
authors.lastname: Burcelin
authors.affiliation: Toulouse III, Institut de Recherche en Santé Digestive (IRSD) Team 3, "Intestinal Neuroimmune Interactions" INSERM U1220, Université Paul Sabatier, Toulouse Cedex 3, France.|European Associated Laboratory NeuroMicrobiota (INSERM/UCL), Bâtiment B - Pavillon Lefebvre, Toulouse Cedex 3, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
authors.affiliation: INSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'Azur, Nice, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Cormont
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France matteo.serino@inserm.fr.|Unité Mixte de Recherche (UMR) 1048, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse Cedex 4, France.
authors.forename: Matteo
authors.identifier: 0000-0003-4644-8532
authors.initials: M
authors.lastname: Serino
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D064806:Dysbiosis; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000382:microbiology*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics
chemical_list: D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)
keywords: gut microbiota transfer; hepatic glucose production; high‐fat diet; metabolic diseases; microbiome