title: Periodontitis induced byPorphyromonas gingivalisdrives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response.
abstract: To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet.
  
  
  
  We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens likePorphyromonas gingivalis(Pg),Fusobacterium nucleatumandPrevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system.
  
  
  
  Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivatedPgprior to the periodontal infection induced specific antibodies againstPgand protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides fromPgmimicked the impact of periodontitis on immune and metabolic parameters.
  
  
  
  We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis.
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.|Faculté de Chirurgie-Dentaire de Toulouse, Technical platform of Research in Odontology, Toulouse Cedex 09, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Blasco-Baque
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Garidou
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Pomié
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Escoula
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.|Faculté de Chirurgie-Dentaire de Toulouse, Technical platform of Research in Odontology, Toulouse Cedex 09, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Loubieres
authors.affiliation: EA 1254 Microbiologie Risques infectieux-2, Rennes Cedex, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Le Gall-David
authors.affiliation: Faculté de Chirurgie-Dentaire de Toulouse, Technical platform of Research in Odontology, Toulouse Cedex 09, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemaitre
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Nicolas
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Klopp
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Waget
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Azalbert
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: André
authors.initials: A
authors.lastname: Colom
authors.affiliation: CHU Rennes et EA 1254 Microbiologie Risques infectieux-2, Rennes Cedex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Bonnaure-Mallet
authors.affiliation: Faculté de Chirurgie-Dentaire de Toulouse, Technical platform of Research in Odontology, Toulouse Cedex 09, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kemoun
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Serino
authors.affiliation: INSERM U1048, Toulouse, France.|Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.|Université Paul Sabatier (UPS), Toulouse, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications*; D017690:Cell Transplantation; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D005881:Gingiva / Q000382:microbiology; D006943:Hyperglycemia / Q000276:immunology / Q000382:microbiology; D007333:Insulin Resistance / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D010518:Periodontitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D016966:Porphyromonas gingivalis / Q000276:immunology; D011897:Random Allocation; D013154:Spleen / Q000166:cytology; D014611:Vaccination
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D007371:Interferon-gamma
keywords: BACTERIAL INFECTION; BACTERIAL PATHOGENESIS; DIABETES MELLITUS; DIET; IMMUNE RESPONSE
references.citation: Curr Cardiol Rep. 2014 Nov;16(11):540
references.pmid: 25303894
references.citation: Genome Biol. 2011 Jun 24;12(6):R60
references.pmid: 21702898
references.citation: J Leukoc Biol. 2014 Aug;96(2):349-57
references.pmid: 24782490
references.citation: Evid Based Dent. 2010;11(3):73-4
references.pmid: 20938470
references.citation: J Clin Endocrinol Metab. 2008 Oct;93(10):3989-94
references.pmid: 18682518
references.citation: Science. 2012 Jun 8;336(6086):1262-7
references.pmid: 22674330
references.citation: Am J Clin Nutr. 2008 May;87(5):1219-23
references.pmid: 18469242
references.citation: Mol Oral Microbiol. 2010 Oct;25(5):305-16
references.pmid: 20883220
references.citation: Diabetologia. 2012 Jan;55(1):21-31
references.pmid: 22057194
references.citation: J Gastroenterol. 2013 Nov;48(11):1259-70
references.pmid: 23307045
references.citation: PLoS One. 2011;6(6):e21184
references.pmid: 21698161
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5
references.pmid: 16033867
references.citation: J Immunol. 2014 May 1;192(9):4103-11
references.pmid: 24683190
references.citation: Acta Diabetol. 2013 Oct;50(5):753-61
references.pmid: 22711164
references.citation: Periodontol 2000. 2007;43:254-66
references.pmid: 17214843
references.citation: Gut. 2012 Apr;61(4):543-53
references.pmid: 22110050
references.citation: Semin Immunol. 2012 Feb;24(1):67-74
references.pmid: 22265028
references.citation: Mol Metab. 2013 Jul 04;2(3):281-91
references.pmid: 24049740
references.citation: PLoS One. 2012;7(11):e48220
references.pmid: 23133617
references.citation: Nature. 2006 Dec 14;444(7121):860-7
references.pmid: 17167474
references.citation: Adv Dent Res. 2014 May;26(1):15-22
references.pmid: 24736700
references.citation: Gut. 2013 Dec;62(12):1764-70
references.pmid: 22990306
references.citation: Endocrinology. 2010 Nov;151(11):5103-13
references.pmid: 20844009
references.citation: Infect Immun. 2013 Mar;81(3):690-6
references.pmid: 23250953
references.citation: Eur J Oral Sci. 2012 Oct;120(5):408-14
references.pmid: 22984998
references.citation: Sci Rep. 2014 May 06;4:4828
references.pmid: 24797416
references.citation: Front Biosci. 2007 May 01;12:3965-74
references.pmid: 17485350
references.citation: Mol Immunol. 2011 Oct;49(1-2):387-94
references.pmid: 21967868
references.citation: J Periodontal Res. 2007 Dec;42(6):559-65
references.pmid: 17956470
references.citation: Periodontol 2000. 2002;29:7-10
references.pmid: 12102700
references.citation: Pathog Dis. 2014 Apr;70(3):408-13
references.pmid: 24532232
references.citation: Pathol Biol (Paris). 2008 Jul;56(5):305-9
references.pmid: 18178333
references.citation: Crit Rev Oral Biol Med. 2002;13(2):132-42
references.pmid: 12097356
references.citation: PLoS One. 2012;7(12):e52606
references.pmid: 23300720
references.citation: Arch Oral Biol. 2014 Feb;59(2):167-75
references.pmid: 24370188
references.citation: J Clin Periodontol. 2005;32 Suppl 6:132-58
references.pmid: 16128835
references.citation: J Periodontol. 2005 Aug;76(8):1282-6
references.pmid: 16101359
references.citation: J Clin Periodontol. 2013 Jun;40(6):591-8
references.pmid: 23534379
references.citation: Physiol Rep. 2013 Oct;1(5):e00079
references.pmid: 24159380
references.citation: BMC Oral Health. 2010 Apr 29;10:10
references.pmid: 20429938
references.citation: Ann Cardiol Angeiol (Paris). 2012 Jun;61(3):173-7
references.pmid: 22621847
references.citation: J Rheumatol. 2010 Jun;37(6):1105-12
references.pmid: 20436074
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4592-8
references.pmid: 20937873
references.citation: Bioinformatics. 2005 Apr 1;21(7):1280-1
references.pmid: 15546938
references.citation: Diabetes. 2007 Jul;56(7):1761-72
references.pmid: 17456850
references.citation: Nat Rev Endocrinol. 2011 Oct 25;8(3):183-92
references.pmid: 22024974
references.citation: J Clin Periodontol. 2014 Jun;41(6):541-9
references.pmid: 24735470
references.citation: Periodontol 2000. 2010 Oct;54(1):207-21
references.pmid: 20712641
references.citation: J Microbiol. 2014 Feb;52(2):154-60
references.pmid: 24500480
references.citation: Oral Microbiol Immunol. 2005 Aug;20(4):244-52
references.pmid: 15943770