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Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> diabetes mice using <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>Pg<\/jats:italic>). We screened for <jats:italic>Pg<\/jats:italic>-specific peptides in the intestinal fecal specimens and examined whether <jats:italic>Pg<\/jats:italic> localization influenced the intestinal microbiota profile, in turn altering the levels of the gut metabolites. We evaluated whether the deterioration in fasting hyperglycemia was related to the changes in the intrahepatic glucose metabolism, using proteome and metabolome analyses. Oral <jats:italic>Pg<\/jats:italic> treatment aggravated both fasting and postprandial hyperglycemia (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), with a significant (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) increase in dental alveolar bone resorption. <jats:italic>Pg<\/jats:italic>-specific peptides were identified in fecal specimens following oral <jats:italic>Pg<\/jats:italic> treatment. The intestinal <jats:italic>Pg<\/jats:italic> profoundly altered the gut microbiome profiles at the phylum, family, and genus levels; <jats:italic>Prevotella<\/jats:italic> exhibited the largest increase in abundance. In addition, <jats:italic>Pg<\/jats:italic>-treatment significantly altered intestinal metabolite levels. Fasting hyperglycemia was associated with the increase in the levels of gluconeogenesis-related enzymes and metabolites without changes in the expression of proinflammatory cytokines and insulin resistance. Oral <jats:italic>Pg<\/jats:italic> administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thus aggravating hyperglycemia in an obese type 2 diabetes mouse model.<\/jats:p>","DOI":"10.1038\/s41598-021-97868-2","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T10:03:59Z","timestamp":1631700239000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model"],"prefix":"10.1038","volume":"11","author":[{"given":"Yoichiro","family":"Kashiwagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Aburaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Narukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatomo","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rentaro","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Tominaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takenori","family":"Nozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Izumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsunori","family":"Kashiwagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Bamba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Ishihama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"97868_CR1","first-page":"RA291","volume":"9","author":"S Amar","year":"2003","unstructured":"Amar, S. & Han, X. 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