title: Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota.
abstract: Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders. To investigate this hypothesis, changes in the gut microbiota, insulin and glucose intolerance, and levels of tissue inflammation were analysed in mice after oral administration of Porphyromonas gingivalis, a representative periodontopathogens. Pyrosequencing revealed that the population belonging to Bacteroidales was significantly elevated in P. gingivalis-administered mice which coincided with increases in insulin resistance and systemic inflammation. In P. gingivalis-administered mice blood endotoxin levels tended to be higher, whereas gene expression of tight junction proteins in the ileum was significantly decreased. These results provide a new paradigm for the interrelationship between periodontitis and systemic diseases.
authors.affiliation: 1] Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan [2] Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Arimatsu
authors.affiliation: 1] Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan [2] Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: 1] Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan [2] Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Miyazawa
authors.affiliation: 1] Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan [2] Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Minagawa
authors.affiliation: 1] Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan [2] Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Mayuka
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Division of Periodontology, Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, USA.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Ryder
authors.affiliation: Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Gotoh
authors.affiliation: Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Motooka
authors.affiliation: Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003773:Dental Plaque / Q000382:microbiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005881:Gingiva / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018149:Glucose Intolerance / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007082:Ileum / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008659:Metabolic Diseases / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D010518:Periodontitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016966:Porphyromonas gingivalis; D062725:Tight Junction Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D062725:Tight Junction Proteins