title: Periodontal dysbiosis linked to periodontitis is associated with cardiometabolic adaptation to high-fat diet in mice.
abstract: Periodontitis and type 2 diabetes are connected pandemic diseases, and both are risk factors for cardiovascular complications. Nevertheless, the molecular factors relating these two chronic pathologies are poorly understood. We have shown that, in response to a long-term fat-enriched diet, mice present particular gut microbiota profiles related to three metabolic phenotypes: diabetic-resistant (DR), intermediate (Inter), and diabetic-sensitive (DS). Moreover, many studies suggest that a dysbiosis of periodontal microbiota could be associated with the incidence of metabolic and cardiac diseases. We investigated whether periodontitis together with the periodontal microbiota may also be associated with these different cardiometabolic phenotypes. We report that the severity of glucose intolerance is related to the severity of periodontitis and cardiac disorders. In detail, alveolar bone loss was more accentuated in DS than Inter, DR, and normal chow-fed mice. Molecular markers of periodontal inflammation, such as TNF-α and plasminogen activator inhibitor-1 mRNA levels, correlated positively with both alveolar bone loss and glycemic index. Furthermore, the periodontal microbiota of DR mice was dominated by the Streptococcaceae family of the phylum Firmicutes, whereas the periodontal microbiota of DS mice was characterized by increased Porphyromonadaceae and Prevotellaceae families. Moreover, in DS mice the periodontal microbiota was indicated by an abundance of the genera Prevotella and Tannerella, which are major periodontal pathogens. PICRUSt analysis of the periodontal microbiome highlighted that prenyltransferase pathways follow the cardiometabolic adaptation to a high-fat diet. Finally, DS mice displayed a worse cardiac phenotype, percentage of fractional shortening, heart rhythm, and left ventricle weight-to-tibia length ratio than Inter and DR mice. Together, our data show that periodontitis combined with particular periodontal microbiota and microbiome is associated with metabolic adaptation to a high-fat diet related to the severity of cardiometabolic alteration.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Maxime
authors.initials: M
authors.lastname: Branchereau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: François
authors.initials: F
authors.lastname: Reichardt
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France; Faculté de Chirurgie-Dentaire de Toulouse, Toulouse, France; and.
authors.forename: Pascale
authors.initials: P
authors.lastname: Loubieres
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Pauline
authors.initials: P
authors.lastname: Marck
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Aurélie
authors.initials: A
authors.lastname: Waget
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Vincent
authors.initials: V
authors.lastname: Azalbert
authors.affiliation: Equipe Intéraction Mycobactériennes avec les Cellules Hôtes, Institute of Pharmacology and Structural Biology, Centre National de la Recherche Scientifique, Toulouse, France.
authors.forename: André
authors.initials: A
authors.lastname: Colom
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Roshan
authors.initials: R
authors.lastname: Padmanabhan
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Anaïs
authors.initials: A
authors.lastname: Giry
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: François
authors.initials: F
authors.lastname: Tercé
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Christophe
authors.initials: C
authors.lastname: Heymes
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Remy
authors.initials: R
authors.lastname: Burcelin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France;
authors.forename: Matteo
authors.initials: M
authors.lastname: Serino
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048 and Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France; Université Paul Sabatier, Toulouse, France; Faculté de Chirurgie-Dentaire de Toulouse, Toulouse, France; and vincent.blasco@inserm.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Blasco-Baque
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism* / Q000382:microbiology; D059305:Diet, High-Fat; D004122:Dimethylallyltranstransferase / Q000378:metabolism; D064806:Dysbiosis / Q000382:microbiology; D018149:Glucose Intolerance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D010518:Periodontitis / Q000150:complications / Q000382:microbiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D018720:Prevotella / Q000302:isolation & purification; D013289:Streptococcaceae / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016276:Ventricular Function
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D004122:Dimethylallyltranstransferase
keywords: high-fat diet; metabolic diseases; periodontal dysbiosis; periodontal microbiome; periodontitis