Obesity-Related Gut Microbiota Aggravates Alveolar Bone Destruction in Experimental Periodontitis through Elevation of Uric Acid

Sato, Keisuke; Yamazaki, Kyoko; Kato, Tamotsu; Nakanishi, Yumiko; Tsuzuno, Takahiro; Yokoji-Takeuchi, Mai; Yamada-Hara, Miki; Miura, Nobuaki; Okuda, Shujiro; Ohno, Hiroshi; Yamazaki, Kazuhisa

doi:10.1128/mbio.00771-21

Cited by 52 publications

(37 citation statements)

References 47 publications

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“…Furthermore, ligature-induced periodontitis caused more severe bone destruction in hyperuricemic mice than in normouricemic mice. They concluded that obesity increases the risk of periodontal disease by increasing the production of uric acid mediated by gut dysbiosis [93].…”

Section: Diabetes and Obesity Model Mice With Ligature-induced Periodontitismentioning

confidence: 99%

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Lin

Niimi

Ohsugi

et al. 2021

IJMS

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Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.

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Section: Diabetes and Obesity Model Mice With Ligature-induced Periodontitismentioning

confidence: 99%

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Lin

Niimi

Ohsugi

et al. 2021

IJMS

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show abstract

“…In present study, we used 16S rRNA gene sequencing to detect the oral microbiota after ligature-induced periodontitis for seven days according to previous study [29,30]. The experimental periods various from 5 days to 60 days [29,31,32] and in this study, we found signi cant alveolar bone loss and in ammatory cells in ltration in the ligature-induced periodontitis group for seven days.…”

Section: Discussionmentioning

confidence: 68%

Pasteurella multocidia toxin aggravates ligatured-induced periodontal bone loss and inflammation via NOD-like receptor protein 3 inflammasome

Han

Gao

Yang

et al. 2022

Preprint

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NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is reportedly involved in periodontal pathogenesis. Pasteurella multocida toxin (PMT) is the major virulence factor of Pasteurella multocida strains, which belongs to the GNFR. The existence of GNFR and their toxin may aggravate periodontitis. Therefore, it’s important to unclose the regulatory mechanisms of PMT in periodontitis. However, the involvement of NLRP3 inflammasome and PMT in periodontitis remain unclear. The results showed that NLRP3 expression was increased in human and mice gingivae from periodontitis patients and periodontitis mice by immunohistochemical staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Nlrp3-/- mice showed less periodontal bone loss and lower abundances of Pasteurella multocida by 16S rRNA sequencing. PMT promoted NLRP3 expressions by activating nuclear factor kappa light chain enhancer of B cells (NF-κB) pathway and activated NLRP3 inflammasome. This effect was reversed by NLRP3 inhibitor MCC950. Furthermore, PMT aggravated periodontal bone loss and inflammation in WT mice while MCC950 attenuated periodontal bone loss and inflammation. The Nlrp3-/- periodontitis models with PMT local injection showed less bone loss and inflammation compared with WT periodontitis mice after PMT treatment. Taken together, our results showed that PMT aggravates periodontal response to the ligature by promoting NLRP3 expression and activating NLRP3 inflammasome, suggesting that NLRP3 may be an effective target for the treatment of periodontitis caused by GNFR and MCC950 may be a potential drug against this disease.

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“…The construction of the EP model and animal experiments were consistent with our previous study ( Fang et al, 2021a ). After 4 weeks of the experiment, the feces of each rat were collected using sterile cryopreservation tubes with a unique label, and frozen at −80°C within 3 h after sampling ( Sato et al, 2021 ). Bilateral maxillary alveolar bone–contained molars were harvested and fixed with 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

Alterations and Correlations of Gut Microbiota and Fecal Metabolome Characteristics in Experimental Periodontitis Rats

Han

Nie

et al. 2022

Front. Microbiol.

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ObjectivesPeriodontitis affects the progression of many diseases, while its detailed mechanism remains unclear. This study hopes to provide new ideas for exploring its mechanism by analyzing the gut microbiota and fecal metabolic characteristics of experimental periodontitis rats.MethodsA total of 10 rats were randomly divided into ligature-induced experimental periodontitis (EP) group and healthy control group. After 4 weeks of the experiment, the feces of all rats were collected for sequencing through 16S ribosomal DNA (rDNA) sequencing technology and liquid chromatography–mass spectrometry (LC–MS).Results16S rDNA sequencing results showed that the β-diversity of gut microbiota was significantly different between the EP and control group, and the levels of dominant genera were different. Compared with the control group, Ruminococcus, Escherichia, and Roseburia were significantly enriched in EP, and Coprococcus, Turicibacter, Lachnospira were significantly decreased. Correlation analysis showed that Roseburia exhibited the highest correlation within the genus. Of 3,488 qualitative metabolites, 164 metabolites were upregulated and 362 metabolites were downregulated in EP. Enrichment analysis showed that periodontitis significantly changed 45 positive/negative ion metabolic pathways. Five KEGG pathways, protein digestion and absorption, tyrosine metabolism, glycolysis/gluconeogenesis, niacin and nicotinamide metabolism, and oxidative phosphorylation, are enriched in both the microbiome and metabolome. Correlation analysis showed that the genera with significant differences in periodontitis were usually significantly correlated with more metabolites, such as Roseburia, Lachnospira, Escherichia, Turicibacter, and Ruminococcus. The genera with the same changing trend tended to have a similar correlation with some certain metabolites. In addition, vitamin D2 and protoporphyrin IX have the most significant correlations with microorganisms.ConclusionOur study reveals that periodontitis alters gut microbiota and fecal metabolites. The correlation analysis of microbiota and metabolome provides a deeper understanding of periodontitis, and also provides a direction for the study of periodontitis affecting other diseases.

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Obesity-Related Gut Microbiota Aggravates Alveolar Bone Destruction in Experimental Periodontitis through Elevation of Uric Acid

Abstract: Obesity is an epidemic health issue with a rapid increase worldwide. It increases the risk of various diseases, including periodontal disease, an oral chronic infectious disease.

Cited by 52 publications

References 47 publications

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Pasteurella multocidia toxin aggravates ligatured-induced periodontal bone loss and inflammation via NOD-like receptor protein 3 inflammasome

Alterations and Correlations of Gut Microbiota and Fecal Metabolome Characteristics in Experimental Periodontitis Rats

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