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 mi...

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Main Authors: Simon Nicolas, Vincent Blasco‐Baque, Audren Fournel, Jerome Gilleron, Pascale Klopp, Aurelie Waget, Franck Ceppo, Alysson Marlin, Roshan Padmanabhan, Jason S Iacovoni, François Tercé, Patrice D Cani, Jean‐François Tanti, Remy Burcelin, Claude Knauf, Mireille Cormont, Matteo Serino
Format: Article
Language:English
Published: Springer Nature 2017-03-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.15252/msb.20167356
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author Simon Nicolas
Vincent Blasco‐Baque
Audren Fournel
Jerome Gilleron
Pascale Klopp
Aurelie Waget
Franck Ceppo
Alysson Marlin
Roshan Padmanabhan
Jason S Iacovoni
François Tercé
Patrice D Cani
Jean‐François Tanti
Remy Burcelin
Claude Knauf
Mireille Cormont
Matteo Serino
author_facet Simon Nicolas
Vincent Blasco‐Baque
Audren Fournel
Jerome Gilleron
Pascale Klopp
Aurelie Waget
Franck Ceppo
Alysson Marlin
Roshan Padmanabhan
Jason S Iacovoni
François Tercé
Patrice D Cani
Jean‐François Tanti
Remy Burcelin
Claude Knauf
Mireille Cormont
Matteo Serino
author_sort Simon Nicolas
collection DOAJ
description 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.
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spelling doaj-art-b955560a33e845d1b23e5d096d6e2b272025-01-12T12:45:37ZengSpringer NatureMolecular Systems Biology1744-42922017-03-0113311710.15252/msb.20167356Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolismSimon Nicolas0Vincent Blasco‐Baque1Audren Fournel2Jerome Gilleron3Pascale Klopp4Aurelie Waget5Franck Ceppo6Alysson Marlin7Roshan Padmanabhan8Jason S Iacovoni9François Tercé10Patrice D Cani11Jean‐François Tanti12Remy Burcelin13Claude Knauf14Mireille Cormont15Matteo Serino16Institut National de la Santé et de la Recherche Médicale (INSERM)Institut National de la Santé et de la Recherche Médicale (INSERM)Toulouse III, Institut de Recherche en Santé Digestive (IRSD) Team 3, “Intestinal Neuroimmune Interactions” INSERM U1220, Université Paul SabatierINSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'AzurInstitut National de la Santé et de la Recherche Médicale (INSERM)Institut National de la Santé et de la Recherche Médicale (INSERM)INSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'AzurToulouse III, Institut de Recherche en Santé Digestive (IRSD) Team 3, “Intestinal Neuroimmune Interactions” INSERM U1220, Université Paul SabatierInstitut National de la Santé et de la Recherche Médicale (INSERM)Institut National de la Santé et de la Recherche Médicale (INSERM)Institut National de la Santé et de la Recherche Médicale (INSERM)Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de LouvainINSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'AzurInstitut National de la Santé et de la Recherche Médicale (INSERM)Toulouse III, Institut de Recherche en Santé Digestive (IRSD) Team 3, “Intestinal Neuroimmune Interactions” INSERM U1220, Université Paul SabatierINSERM Unité 1065/Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'AzurInstitut National de la Santé et de la Recherche Médicale (INSERM)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.https://doi.org/10.15252/msb.20167356gut microbiota transferhepatic glucose productionhigh‐fat dietmetabolic diseasesmicrobiome
spellingShingle Simon Nicolas
Vincent Blasco‐Baque
Audren Fournel
Jerome Gilleron
Pascale Klopp
Aurelie Waget
Franck Ceppo
Alysson Marlin
Roshan Padmanabhan
Jason S Iacovoni
François Tercé
Patrice D Cani
Jean‐François Tanti
Remy Burcelin
Claude Knauf
Mireille Cormont
Matteo Serino
Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism
Molecular Systems Biology
gut microbiota transfer
hepatic glucose production
high‐fat diet
metabolic diseases
microbiome
title Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism
title_full Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism
title_fullStr Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism
title_full_unstemmed Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism
title_short Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism
title_sort transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism
topic gut microbiota transfer
hepatic glucose production
high‐fat diet
metabolic diseases
microbiome
url https://doi.org/10.15252/msb.20167356
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