Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

Abstract Periodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the...

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Autores principales: Yoichiro Kashiwagi, Shunsuke Aburaya, Naoyuki Sugiyama, Yuki Narukawa, Yuta Sakamoto, Masatomo Takahashi, Hayato Uemura, Rentaro Yamashita, Shotaro Tominaga, Satoko Hayashi, Takenori Nozaki, Satoru Yamada, Yoshihiro Izumi, Atsunori Kashiwagi, Takeshi Bamba, Yasushi Ishihama, Shinya Murakami
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:06dbafb43c554a6c8bc8b1479388ef002021-12-02T15:15:35ZPorphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model10.1038/s41598-021-97868-22045-2322https://doaj.org/article/06dbafb43c554a6c8bc8b1479388ef002021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97868-2https://doaj.org/toc/2045-2322Abstract Periodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the intestinal fecal specimens and examined whether Pg 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 Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05), with a significant (P < 0.01) increase in dental alveolar bone resorption. Pg-specific peptides were identified in fecal specimens following oral Pg treatment. The intestinal Pg profoundly altered the gut microbiome profiles at the phylum, family, and genus levels; Prevotella exhibited the largest increase in abundance. In addition, Pg-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 Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thus aggravating hyperglycemia in an obese type 2 diabetes mouse model.Yoichiro KashiwagiShunsuke AburayaNaoyuki SugiyamaYuki NarukawaYuta SakamotoMasatomo TakahashiHayato UemuraRentaro YamashitaShotaro TominagaSatoko HayashiTakenori NozakiSatoru YamadaYoshihiro IzumiAtsunori KashiwagiTakeshi BambaYasushi IshihamaShinya MurakamiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yoichiro Kashiwagi
Shunsuke Aburaya
Naoyuki Sugiyama
Yuki Narukawa
Yuta Sakamoto
Masatomo Takahashi
Hayato Uemura
Rentaro Yamashita
Shotaro Tominaga
Satoko Hayashi
Takenori Nozaki
Satoru Yamada
Yoshihiro Izumi
Atsunori Kashiwagi
Takeshi Bamba
Yasushi Ishihama
Shinya Murakami
Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model
description Abstract Periodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the intestinal fecal specimens and examined whether Pg 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 Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05), with a significant (P < 0.01) increase in dental alveolar bone resorption. Pg-specific peptides were identified in fecal specimens following oral Pg treatment. The intestinal Pg profoundly altered the gut microbiome profiles at the phylum, family, and genus levels; Prevotella exhibited the largest increase in abundance. In addition, Pg-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 Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thus aggravating hyperglycemia in an obese type 2 diabetes mouse model.
format article
author Yoichiro Kashiwagi
Shunsuke Aburaya
Naoyuki Sugiyama
Yuki Narukawa
Yuta Sakamoto
Masatomo Takahashi
Hayato Uemura
Rentaro Yamashita
Shotaro Tominaga
Satoko Hayashi
Takenori Nozaki
Satoru Yamada
Yoshihiro Izumi
Atsunori Kashiwagi
Takeshi Bamba
Yasushi Ishihama
Shinya Murakami
author_facet Yoichiro Kashiwagi
Shunsuke Aburaya
Naoyuki Sugiyama
Yuki Narukawa
Yuta Sakamoto
Masatomo Takahashi
Hayato Uemura
Rentaro Yamashita
Shotaro Tominaga
Satoko Hayashi
Takenori Nozaki
Satoru Yamada
Yoshihiro Izumi
Atsunori Kashiwagi
Takeshi Bamba
Yasushi Ishihama
Shinya Murakami
author_sort Yoichiro Kashiwagi
title Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model
title_short Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model
title_full Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model
title_fullStr Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model
title_full_unstemmed Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model
title_sort porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/06dbafb43c554a6c8bc8b1479388ef00
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