Celine Pomié1,2,3, Florence Servant4, Lucile Garidou1,2, Vincent Azalbert1,2, Aurélie Waget1,2, Pascale Klopp1,2, Céline Garret1,2, Julie Charpentier1,2, Francois Briand5, Thierry Sulpice5, Benjamin Lelouvier4, Victorine Douin-Echinard6,7, Rémy Burcelin8,9. 1. Institut National de La Santé et de la Recherche Médicale (INSERM), Toulouse, France. 2. Unité Mixte de Recherche (UMR) 1297, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2: 'Intestinal Risk Factors, Diabetes, Dyslipidemia', Université Paul Sabatier (UPS), 31432, Toulouse Cedex 4, France. 3. Evotec, Toulouse, France. 4. VAIOMER, Prologue Biotech, Rue Pierre et Marie Curie, Labège Innopole, France. 5. PHYSIOGENEX, Prologue Biotech, Rue Pierre et Marie Curie, Labège Innopole, France. 6. Institut National de La Santé et de la Recherche Médicale (INSERM), Toulouse, France. victorine.douin@inserm.fr. 7. Unité Mixte de Recherche (UMR) 1297, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2: 'Intestinal Risk Factors, Diabetes, Dyslipidemia', Université Paul Sabatier (UPS), 31432, Toulouse Cedex 4, France. victorine.douin@inserm.fr. 8. Institut National de La Santé et de la Recherche Médicale (INSERM), Toulouse, France. remy.burcelin@inserm.fr. 9. Unité Mixte de Recherche (UMR) 1297, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2: 'Intestinal Risk Factors, Diabetes, Dyslipidemia', Université Paul Sabatier (UPS), 31432, Toulouse Cedex 4, France. remy.burcelin@inserm.fr.
Abstract
OBJECTIVE: The intestinal microbiota to immune system crosstalk is a major regulator of metabolism and hence metabolic diseases. An impairment of the chemokine receptor CX3CR1, as a key regulator shaping intestinal microbiota under normal chow feeding, could be one of the early events of dysglycemia. METHODS: We studied the gut microbiota ecology by sequencing the gut and tissue microbiota. We studied its role in energy metabolism in CX3CR1-deficent and control mice using various bioassays notably the glycemic regulation during fasting and the respiratory quotient as two highly sensitive physiological features. We used antibiotics and prebiotics treatments, and germ free mouse colonization. RESULTS: We identify that CX3CR1 disruption impairs gut microbiota ecology and identified a specific signature associated to the genotype. The glycemic control during fasting and the respiratory quotient throughout the day are deeply impaired. A selected four-week prebiotic treatment modifies the dysbiotic microbiota and improves the fasting state glycemic control of the CX3CR1-deficent mice and following a glucose tolerance test. A 4 week antibiotic treatment also improves the glycemic control as well. Eventually, germ free mice colonized with the microbiota from CX3CR1-deficent mice developed glucose intolerance. CONCLUSIONS: CX3CR1 is a molecular mechanism in the control of the gut microbiota ecology ensuring the maintenance of a steady glycemia and energy metabolism. Its impairment could be an early mechanism leading to gut microbiota dysbiosis and the onset of metabolic disease.
OBJECTIVE: The intestinal microbiota to immune system crosstalk is a major regulator of metabolism and hence metabolic diseases. An impairment of the chemokine receptor CX3CR1, as a key regulator shaping intestinal microbiota under normal chow feeding, could be one of the early events of dysglycemia. METHODS: We studied the gut microbiota ecology by sequencing the gut and tissue microbiota. We studied its role in energy metabolism in CX3CR1-deficent and control mice using various bioassays notably the glycemic regulation during fasting and the respiratory quotient as two highly sensitive physiological features. We used antibiotics and prebiotics treatments, and germ free mouse colonization. RESULTS: We identify that CX3CR1 disruption impairs gut microbiota ecology and identified a specific signature associated to the genotype. The glycemic control during fasting and the respiratory quotient throughout the day are deeply impaired. A selected four-week prebiotic treatment modifies the dysbiotic microbiota and improves the fasting state glycemic control of the CX3CR1-deficent mice and following a glucose tolerance test. A 4 week antibiotic treatment also improves the glycemic control as well. Eventually, germ free mice colonized with the microbiota from CX3CR1-deficent mice developed glucose intolerance. CONCLUSIONS:CX3CR1 is a molecular mechanism in the control of the gut microbiota ecology ensuring the maintenance of a steady glycemia and energy metabolism. Its impairment could be an early mechanism leading to gut microbiota dysbiosis and the onset of metabolic disease.
Authors: Helle Krogh Pedersen; Valborg Gudmundsdottir; Henrik Bjørn Nielsen; Tuulia Hyotylainen; Trine Nielsen; Benjamin A H Jensen; Kristoffer Forslund; Falk Hildebrand; Edi Prifti; Gwen Falony; Emmanuelle Le Chatelier; Florence Levenez; Joel Doré; Ismo Mattila; Damian R Plichta; Päivi Pöhö; Lars I Hellgren; Manimozhiyan Arumugam; Shinichi Sunagawa; Sara Vieira-Silva; Torben Jørgensen; Jacob Bak Holm; Kajetan Trošt; Karsten Kristiansen; Susanne Brix; Jeroen Raes; Jun Wang; Torben Hansen; Peer Bork; Søren Brunak; Matej Oresic; S Dusko Ehrlich; Oluf Pedersen Journal: Nature Date: 2016-07-13 Impact factor: 49.962
Authors: Manimozhiyan Arumugam; Jeroen Raes; Eric Pelletier; Denis Le Paslier; Takuji Yamada; Daniel R Mende; Gabriel R Fernandes; Julien Tap; Thomas Bruls; Jean-Michel Batto; Marcelo Bertalan; Natalia Borruel; Francesc Casellas; Leyden Fernandez; Laurent Gautier; Torben Hansen; Masahira Hattori; Tetsuya Hayashi; Michiel Kleerebezem; Ken Kurokawa; Marion Leclerc; Florence Levenez; Chaysavanh Manichanh; H Bjørn Nielsen; Trine Nielsen; Nicolas Pons; Julie Poulain; Junjie Qin; Thomas Sicheritz-Ponten; Sebastian Tims; David Torrents; Edgardo Ugarte; Erwin G Zoetendal; Jun Wang; Francisco Guarner; Oluf Pedersen; Willem M de Vos; Søren Brunak; Joel Doré; María Antolín; François Artiguenave; Hervé M Blottiere; Mathieu Almeida; Christian Brechot; Carlos Cara; Christian Chervaux; Antonella Cultrone; Christine Delorme; Gérard Denariaz; Rozenn Dervyn; Konrad U Foerstner; Carsten Friss; Maarten van de Guchte; Eric Guedon; Florence Haimet; Wolfgang Huber; Johan van Hylckama-Vlieg; Alexandre Jamet; Catherine Juste; Ghalia Kaci; Jan Knol; Omar Lakhdari; Severine Layec; Karine Le Roux; Emmanuelle Maguin; Alexandre Mérieux; Raquel Melo Minardi; Christine M'rini; Jean Muller; Raish Oozeer; Julian Parkhill; Pierre Renault; Maria Rescigno; Nicolas Sanchez; Shinichi Sunagawa; Antonio Torrejon; Keith Turner; Gaetana Vandemeulebrouck; Encarna Varela; Yohanan Winogradsky; Georg Zeller; Jean Weissenbach; S Dusko Ehrlich; Peer Bork Journal: Nature Date: 2011-04-20 Impact factor: 49.962
Authors: Antonio Molinaro; Robert Caesar; Louise Mannerås Holm; Valentina Tremaroli; Patrice D Cani; Fredrik Bäckhed Journal: Mol Metab Date: 2017-09-21 Impact factor: 7.422