Untargeted and targeted gingival metabolome in rodents reveal metabolic links between high‐fat diet‐induced obesity and periodontitis

Chen, Ziyun; Xu, Ting; Liang, Zhanhua; Zhao, Li; Xiong, Xiao-Qing; Xie, Kunke; Yu, Wenxia; Zeng, Xiao‐Wen; Gao, Jie; Zhou, Yinghong; Luo, Gang; Takata, Yasuyuki

doi:10.1111/jcpe.13486

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…Compared with healthy counterparts, periodontitis and a high-fat diet had distinct effects on the gingival metabolome. The metabolomic impact of periodontitis was generally greater in high-fat diet mice than in lean controls [92]. Another study performed fecal microbiota transplantation and ligature-induced periodontitis in mice with high-fat diet-induced obesity and demonstrated that gut dysbiosis-associated metabolites from high-fat diet-fed mice worsen alveolar bone destruction.…”

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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“…More and more research evidence shows that the changes of gut microbiota affect the levels of metabolites, leading to the development of insulin resistance, atherosclerosis, and other diseases ( Lin and Zhang, 2017 ; Canfora et al, 2019 ; Verhaar et al, 2020 ). Chen et al (2021) showed that compared with healthy controls, periodontitis and high-fat diet had a significant impact on gingival metabolome, and experiments verified that high-fat diet had a superimposed effect on metabolome such as arginine metabolism in the presence of periodontitis. A recent animal study suggested that the periodontal pathogen P. gingivalis may increase insulin resistance and circulating branched-chain amino acids elevation through its metabolic activity ( Tian et al, 2020 ).…”

Section: Discussionmentioning

confidence: 94%

“… Sakanaka et al (2021) explored the potential link between periodontitis and cardiometabolic diseases by studying metabolites. Previous studies have pointed out that the use of metabolomics to study the relationship between periodontitis and obesity gets significantly more outputs than the pure oral microbiome ( Chen et al, 2021 ). At present, 16S rDNA sequencing technology is mostly used in the analysis of the gut microbiome, but this technology has the limitation of lacking quantitative functional annotation.…”

Section: Introductionmentioning

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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“…Animal studies have indicated that an increased alveolar bone loss in obese animals with PD and significantly greater alveolar bone loss in obese rats than in lean controls ( 12 , 13 ). In addition, obese individuals who consume an excessively high-fat diet have an enhanced metabolic response to PD and show a metabolic susceptibility to increased periodontal destruction ( 14 ). These findings highlighted the existence of an association between OB and PD.…”

Section: Introductionmentioning

confidence: 99%

“…A growing body of clinical and experimental evidence suggests that immune cell infiltration and inflammatory factors play a critical role in the development of OB or PD ( 2 , 14 ). On the one hand, mouse models of OB and diabetes were found to be characterized by impaired T and B lymphocyte-mediated immune responses ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis

Cai

Zuo

et al. 2023

Front. Immunol.

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BackgroundBoth obesity (OB) and periodontitis (PD) are chronic non-communicable diseases, and numerous epidemiological studies have demonstrated the association between these two diseases. However, the molecular mechanisms that could explain the association between OB and PD are largely unclear. This study aims to investigate the common gene signatures and biological pathways in OB and PD through bioinformatics analysis of publicly available transcriptome datasets.MethodsThe RNA expression profile datasets of OB (GSE104815) and PD (GSE106090) were used as training data, and GSE152991 and GSE16134 as validation data. After screening for differentially expressed genes (DEGs) shared by OB and PD, gene enrichment analysis, protein-protein interaction (PPI) network construction, GeneMANIA analysis, immune infiltration analysis and gene set enrichment analysis (GSEA) were performed. In addition, receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the hub gene. Finally, we constructed the hub gene-associated TF-miRNA-mRNA regulatory network.ResultsWe identified a total of 147 DEGs shared by OB and PD (38 down-regulated and 109 up-regulated). Functional analysis showed that these genes were mainly enriched in immune-related pathways such as B cell receptor signalling, leukocyte migration and cellular defence responses. 14 hub genes (FGR, MNDA, NCF2, FYB1, EVI2B, LY86, IGSF6, CTSS, CXCR4, LCK, FCN1, CXCL2, P2RY13, MMP7) showed high sensitivity and specificity in the ROC curve analysis. The results of immune infiltration analysis showed that immune cells such as macrophages, activated CD4 T cells and immune B cells were present at high infiltration levels in both OB and PD samples.The results of GeneMANIA analysis and GSEA analysis suggested that five key genes (FGR, LCK, FYB1, LY86 and P2RY13) may be strongly associated with macrophages. Finally, we constructed a TF-miRNA-mRNA regulatory network consisting of 233 transcription factors (TFs), 8 miRNAs and 14 mRNAs based on the validated information obtained from the database.ConclusionsFive key genes (FGR, LCK, FYB1, LY86, P2RY13) may be important biomarkers of OB and PD. These genes may play an important role in the pathogenesis of OB and PD by affecting macrophage activity and participating in immune regulation and inflammatory responses.

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Untargeted and targeted gingival metabolome in rodents reveal metabolic links between high‐fat diet‐induced obesity and periodontitis

Cited by 8 publications

References 52 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

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

Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis

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