title: Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver.
abstract: Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease.
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; 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: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; 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: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kato
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; Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuda
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; 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: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
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: D000284:Administration, Oral; D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications* / Q000382:microbiology; D064806:Dysbiosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D019446:Endotoxemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004755:Enterobacteriaceae / Q000502:physiology; D004756:Enterobacteriaceae Infections / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016966:Porphyromonas gingivalis / Q000502:physiology*; D012336:RNA, Ribosomal, 16S
chemical_list: D018836:Inflammation Mediators; D012336:RNA, Ribosomal, 16S