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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97868-2 |
| _version_ | 1818422512175808512 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T13:27:26Z |
| format | Article |
| id | doaj.art-06dbafb43c554a6c8bc8b1479388ef00 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:27:26Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-06dbafb43c554a6c8bc8b1479388ef002022-12-21T22:59:48ZengNature PortfolioScientific Reports2045-23222021-09-0111111610.1038/s41598-021-97868-2Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse modelYoichiro Kashiwagi0Shunsuke Aburaya1Naoyuki Sugiyama2Yuki Narukawa3Yuta Sakamoto4Masatomo Takahashi5Hayato Uemura6Rentaro Yamashita7Shotaro Tominaga8Satoko Hayashi9Takenori Nozaki10Satoru Yamada11Yoshihiro Izumi12Atsunori Kashiwagi13Takeshi Bamba14Yasushi Ishihama15Shinya Murakami16Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of DentistryDivision of Metabolomics, Medical Institute of Bioregulation, Kyushu UniversityGraduate School of Pharmaceutical Sciences, Kyoto UniversityDepartment of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of DentistryGraduate School of Pharmaceutical Sciences, Kyoto UniversityDivision of Metabolomics, Medical Institute of Bioregulation, Kyushu UniversityGraduate School of Pharmaceutical Sciences, Kyoto UniversityGraduate School of Pharmaceutical Sciences, Kyoto UniversityDepartment of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of DentistryDepartment of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of DentistryDivision for Interdisciplinary Dentistry, Osaka University Dental HospitalDepartment of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of DentistryDivision of Metabolomics, Medical Institute of Bioregulation, Kyushu UniversityKusatsu General HospitalDivision of Metabolomics, Medical Institute of Bioregulation, Kyushu UniversityGraduate School of Pharmaceutical Sciences, Kyoto UniversityDepartment of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of DentistryAbstract 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.https://doi.org/10.1038/s41598-021-97868-2 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-97868-2 |
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