Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model.
Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model.
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DOI：
10.1038/s41598-021-97868-2
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发表时间：
2021-09-15
影响因子：
4.6
通讯作者：
Murakami S
中科院分区：
文献类型：
--
作者：
Kashiwagi Y;Aburaya S;Sugiyama N;Narukawa Y;Sakamoto Y;Takahashi M;Uemura H;Yamashita R;Tominaga S;Hayashi S;Nozaki T;Yamada S;Izumi Y;Kashiwagi A;Bamba T;Ishihama Y;Murakami S
牙周炎感染引起全身性炎症;因此，加重糖尿病。口服牙周病原体可能直接改变肠道微生物群。我们使用牙龈卟啉单胞菌（Pg）口服治疗肥胖db/db糖尿病小鼠。我们在肠道粪便标本中筛选了Pg特异性肽，并检查了Pg定位是否影响肠道微生物群，进而改变肠道代谢产物的水平。我们使用蛋白质组和代谢组分析来评估空腹高血糖的恶化是否与肝内葡萄糖代谢的变化有关。口服前列腺素可加重空腹和餐后高血糖（P < 0.05），牙槽骨吸收显著增加（P < 0.01）。在口服Pg治疗后的粪便标本中鉴定出Pg特异性肽。肠道Pg在门、科和属水平上深刻地改变了肠道微生物组谱;普雷沃菌属表现出丰度的最大增加。此外，PG治疗显着改变肠道代谢物水平。空腹高血糖与促新生血管生成相关酶和代谢物水平的增加相关，而促炎细胞因子的表达和胰岛素抵抗没有变化。口服Pg给药诱导肠道微生物群变化，导致肠-肝代谢紊乱，从而加重肥胖2型糖尿病小鼠模型的高血糖症。
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.
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Keystone-Pathogen假设。
DOI：
10.1038/nrmicro2873
发表时间：
2012-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Arimatsu K;Yamada H;Miyazawa H;Minagawa T;Nakajima M;Ryder MI;Gotoh K;Motooka D;Nakamura S;Iida T;Yamazaki K
通讯作者：
Yamazaki K
影响因子：
1.9
作者：
Mortensen, PB;Clausen, MR
通讯作者：
Clausen, MR
影响因子：
4.3
作者：
Cutler, CW;Machen, RL;Iacopino, AM
通讯作者：
Iacopino, AM
影响因子：
5.6
作者：
Kim, Young-Je;Jung, Un Ju
通讯作者：
Jung, Un Ju