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Identification of Potential Oral Microbial Biomarkers for the Diagnosis of Periodontitis.

ABSTRACT: Periodontitis is a chronic and multifactorial inflammatory disease that can lead to tooth loss. At present, the diagnosis for periodontitis is primarily based on clinical examination and radiographic parameters. Detecting the periodontal pathogens at the subgingival plaque requires skilled professionals to collect samples. Periodontal pathogens are also detected on various mucous membranes in patients with periodontitis. In this study, we characterized the oral microbiome profiles from buccal mucosa and supragingival space in a total of 272 healthy subjects as a control group, and periodontitis patients as a disease group. We identified 13 phyla, 193 genera, and 527 species and determined periodontitis-associated taxa. Porphyromonas gingivalis, Tannerella forsythia, Treponema denticolar, Filifactor alocis, Porphyromonas endodontalis, Fretibacterium fastiosum and Peptostreptococcus species were significantly increased in both the buccal mucosa and the supragingival space in periodontitis patients. The identified eight periodontitis-associated bacterial species were clinically validated in an independent cohort. We generated the prediction model based on the oral microbiome profiles using five machine learning algorithms, and validated its capability in predicting the status of patients with periodontitis. The results showed that the oral microbiome profiles from buccal mucosa and supragingival space can represent the microbial composition of subgingival plaque and further be utilized to identify potential microbial biomarkers for the diagnosis of periodontitis. Besides, bacterial community interaction network analysis found distinct patterns associated with dysbiosis in periodontitis. In summary, we have identified oral bacterial species from buccal and supragingival sites which can predict subgingival bacterial composition and can be used for early diagnosis of periodontitis. Therefore, our study provides an important basis for developing easy and noninvasive methods to diagnose and monitor periodontitis.

SUBMITTER: Na HS

PROVIDER: S-EPMC7290295 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Identification of Potential Oral Microbial Biomarkers for the Diagnosis of Periodontitis.

Na Hee Sam HS Kim Si Yeong SY Han Hyejung H Kim Hyun-Joo HJ Lee Ju-Youn JY Lee Jae-Hyung JH Chung Jin J

Journal of clinical medicine 20200520 5

Periodontitis is a chronic and multifactorial inflammatory disease that can lead to tooth loss. At present, the diagnosis for periodontitis is primarily based on clinical examination and radiographic parameters. Detecting the periodontal pathogens at the subgingival plaque requires skilled professionals to collect samples. Periodontal pathogens are also detected on various mucous membranes in patients with periodontitis. In this study, we characterized the oral microbiome profiles from buccal mu ...[more]

PMID: 32443919

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Project description:This study compared the subgingival microbiota of subjects with refractory periodontitis (RP) to those in subjects with treatable periodontitis (GRs = good responders) or periodontal health (PH) using the Human Oral Microbe Identification Microarray (HOMIM).At baseline, subgingival plaque samples were taken from 47 subjects with periodontitis and 20 individuals with PH and analyzed for the presence of 300 species by HOMIM. The subjects with periodontitis were classified as having RP (n = 17) based on mean attachment loss (AL) and/or more than three sites with AL >or=2.5 mm after scaling and root planing, surgery, and systemically administered amoxicillin and metronidazole or as GRs (n = 30) based on mean attachment gain and no sites with AL >or=2.5 mm after treatment. Significant differences in taxa among the groups were sought using the Kruskal-Wallis and chi(2) tests.More species were detected in patients with disease (GR or RP) than in those without disease (PH). Subjects with RP were distinguished from GRs or those with PH by a significantly higher frequency of putative periodontal pathogens, such as Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros), Campylobacter gracilis, Eubacterium nodatum, Selenomonas noxia, Tannerella forsythia (previously T. forsythensis), Porphyromonas gingivalis, Prevotella spp., Treponema spp., and Eikenella corrodens, as well as unusual species (Pseudoramibacter alactolyticus, TM7 spp. oral taxon [OT] 346/356, Bacteroidetes sp. OT 272/274, Solobacterium moorei, Desulfobulbus sp. OT 041, Brevundimonas diminuta, Sphaerocytophaga sp. OT 337, Shuttleworthia satelles, Filifactor alocis, Dialister invisus/pneumosintes, Granulicatella adiacens, Mogibacterium timidum, Veillonella atypica, Mycoplasma salivarium, Synergistes sp. cluster II, and Acidaminococcaceae [G-1] sp. OT 132/150/155/148/135) (P <0.05). Species that were more prevalent in subjects with PH than in patients with periodontitis included Actinomyces sp. OT 170, Actinomyces spp. cluster I, Capnocytophaga sputigena, Cardiobacterium hominis, Haemophilus parainfluenzae, Lautropia mirabilis, Propionibacterium propionicum, Rothia dentocariosa/mucilaginosa, and Streptococcus sanguinis (P <0.05).As determined by HOMIM, patients with RP presented a distinct microbial profile compared to patients in the GR and PH groups.

Project description:Hepatocellular carcinoma (HCC) has a high mortality rate owing to its complexity. Identification of abnormally expressed genes in HCC tissues compared to those in normal liver tissues is a viable strategy for investigating the mechanisms of HCC tumorigenesis and progression as a means of developing novel treatments. A significant advantage of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) is that the data therein were collected from different independent researchers and may be integrated, allowing for a more robust data analysis. Accordingly, in the present study, the gene expression profiles for HCC and control samples were downloaded from the GEO and TCGA. Functional enrichment analysis was performed using a Metascape dataset, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/proteins (STRING) online database. The prognostic value of mRNA for HCC was assessed using the Kaplan-Meier Plotter, a public online tool. A gene mRNA heatmap and DNA amplification numbers were obtained from cBioPortal. A total of 2,553 upregulated genes were identified. Functional enrichment analysis revealed that these differentially expressed genes (DEGs) were mainly accumulated in metabolism of RNA and the cell cycle. Considering the complexity and heterogeneity of the molecular alterations in HCC, multiple genes for the prognostication of patients with HCC are more reliable than a single gene. Thus, the PPI network and univariate Cox regression analysis were applied to screen candidate genes (small nuclear ribonucleoprotein polypeptide B and B1, nucleoporin 37, Rac GTPase activating protein 1, kinesin family member 20A, minichromosome maintenance 10 replication initiation factor, ubiquitin conjugating enzyme E2 C and hyaluronan mediated motility receptor) that are associated with the overall survival and progression-free survival of patients with HCC. In conclusion, the present study identified a set of genes that are associated with overall survival and progression-free survival of patients with HCC, providing valuable information for the prognosis of HCC.

Project description:Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell's neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.'s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li & Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher's exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or 'phenotype' of community assembly), it does not seem to cause the 'mutation' of the 'genotype" (mechanism) of community assembly. We argue that the 'phenotypic' changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation.

Project description:BackgroundOral lichen planus (OLP) is a chronic autoimmune oral mucosal disease that seriously affects the life quality of the patients. But till now, the exact etiology and pathogenesis of OLP remain unclear. Our study is aimed at finding the key molecules and pathways involved in the pathogenesis mechanisms of OLP, providing more effective therapeutic strategies for OLP.MethodsData from GSE52130 were downloaded from GEO datasets for analysis. Then, we carried out enrichment analysis of the differentially expressed genes (DEGs) using Gene Ontology (GO) and KEGG pathway analyses. Next, the CIBERSORT algorithm was used to assess immune cell infiltration in OLP patients. Furthermore, we also constructed a protein-protein interaction network using STRING and Cytoscape and simultaneously sought potential transcription factors plug-in including MCODE CytoHubba and iRegulon. In addition, ROC analysis was employed to assess the diagnostic performance of these hub genes. Lastly, we identified 6 promising novel drugs to treat OLP through Connectivity Map.ResultsWe illustrated that 255 DEGs were mainly enriched in the focal adhesion pathway and metabolism pathways. Besides, Cibersort analysis showed that M1 macrophages, T follicular helper cells, and T regulatory cells are more infiltrated in OLP samples. In addition, ROC analysis demonstrated that these hub genes owned higher diagnostic value in OLP, in which SPRR1B had the highest diagnostic value. And we also predicted that SOX7 was the most relevant transcription factor of those hub genes. Lastly, through the CMap database, we identified 6 small molecules as possible treatment drugs of OLP.ConclusionOur research identified that SPRR1B could be used as potential biomarkers for the early diagnosis of OLP. In addition, as a chronic autoimmune oral mucosal disease, OLP has different infiltration types of immune cells. Furthermore, 6 small molecules were proposed as promising novel treatment drugs for OLP patients. Therefore, our research may provide new impetus for the development of effective OLP biological treatment options.

Project description:BackgroundOral microbiota is closely related to the homeostasis of the oral cavity and lungs. To provide potential information for the prediction, screening, and treatment strategies of individuals, this study compared and investigated the bacterial signatures in periodontitis and chronic obstructive pulmonary disease (COPD).Materials and methodsWe collected subgingival plaque and gingival crevicular fluid samples from 112 individuals (31 healthy controls, 24 patients with periodontitis, 28 patients with COPD, and 29 patients with both periodontitis and COPD). The oral microbiota was analyzed using 16S rRNA gene sequencing and diversity and functional prediction analysis were performed.ResultsWe observed higher bacterial richness in individuals with periodontitis in both types of oral samples. Using LEfSe and DESeq2 analyses, we found differentially abundant genera that may be potential biomarkers for each group. Mogibacterium is the predominant genus in COPD. Ten genera, including Desulfovibrio, Filifactor, Fretibacterium, Moraxella, Odoribacter, Pseudoramibacter Pyramidobacter, Scardovia, Shuttleworthia and Treponema were predominant in periodontitis. Bergeyella, Lautropia, Rothia, Propionibacterium and Cardiobacterium were the signature of the healthy controls. The significantly different pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) between healthy controls and other groups were concentrated in genetic information processing, translation, replication and repair, and metabolism of cofactors and vitamins.ConclusionsWe found the significant differences in the bacterial community and functional characterization of oral microbiota in periodontitis, COPD and comorbid diseases. Compared to gingival crevicular fluid, subgingival plaque may be more appropriate for reflecting the difference of subgingival microbiota in periodontitis patients with COPD. These results may provide potentials for predicting, screening, and treatment strategies for individuals with periodontitis and COPD.

Dataset Information

Identification of Potential Oral Microbial Biomarkers for the Diagnosis of Periodontitis.

Publications

Identification of Potential Oral Microbial Biomarkers for the Diagnosis of Periodontitis.

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