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Identification of Salivary Microbiota and Its Association With Host Inflammatory Mediators in Periodontitis.

ABSTRACT: Periodontitis is a microbial-induced chronic inflammatory disease, which may not only result in tooth loss, but can also contribute to the development of various systemic diseases. The transition from healthy to diseased periodontium depends on microbial dysbiosis and impaired host immune response. Although periodontitis is a common disease as well as associated with various systemic inflammatory conditions, the taxonomic profiling of the salivary microbiota in periodontitis and its association with host immune and inflammatory mediators has not been reported. Therefore, the aim of this study was to identify key pathogens and their potential interaction with the host's inflammatory mediators in saliva samples for periodontitis risk assessment. The microbial 16S rRNA gene sequencing and the levels of inflammatory mediators were performed in saliva samples from patients with chronic periodontitis and periodontally healthy control subjects. The salivary microbial community composition differed significantly between patients with chronic periodontitis and healthy controls. Our analyses identified a number of microbes, including bacteria assigned to Eubacterium saphenum, Tannerella forsythia, Filifactor alocis, Streptococcus mitis/parasanguinis, Parvimonas micra, Prevotella sp., Phocaeicola sp., and Fretibacterium sp. as more abundant in periodontitis, compared to healthy controls. In samples from healthy individuals, we identified Campylobacter concisus, and Veillonella sp. as more abundant. Integrative analysis of the microbiota and inflammatory mediators/cytokines revealed associations that included positive correlations between the pathogens Treponema sp. and Selenomas sp. and the cytokines chitinase 3-like 1, sIL-6R?, sTNF-R1, and gp130/sIL-6R?. In addition, a negative correlation was identified between IL-10 and Filifactor alocis. Our results reveal distinct and disease-specific patterns of salivary microbial composition between patients with periodontitis and healthy controls, as well as significant correlations between microbiota and host-mediated inflammatory cytokines. The positive correlations between the pathogens Treponema sp. and Selenomas sp. and the cytokines chitinase 3-like 1, sIL-6R?, sTNF-R1, and gp130/sIL-6R? might have the future potential to serve as a combined bacteria-host salivary biomarker panel for diagnosis of the chronic infectious disease periodontitis. However, further studies are required to determine the capacity of these microbes and inflammatory mediators as a salivary biomarker panel for periodontitis.

SUBMITTER: Lundmark A

PROVIDER: S-EPMC6598052 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification of Salivary Microbiota and Its Association With Host Inflammatory Mediators in Periodontitis.

Lundmark Anna A Hu Yue O O YOO Huss Mikael M Johannsen Gunnar G Andersson Anders F AF Yucel-Lindberg Tülay T

Frontiers in cellular and infection microbiology 20190621

Periodontitis is a microbial-induced chronic inflammatory disease, which may not only result in tooth loss, but can also contribute to the development of various systemic diseases. The transition from healthy to diseased periodontium depends on microbial dysbiosis and impaired host immune response. Although periodontitis is a common disease as well as associated with various systemic inflammatory conditions, the taxonomic profiling of the salivary microbiota in periodontitis and its association ...[more]

PMID: 31281801

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Project description:ObjectivesPeriodontitis and rheumatoid arthritis (RA) are two widespread chronic inflammatory diseases with a previously suggested association. The objective of the current study was to compare the oral microbial composition and host´s inflammatory mediator profile of saliva samples obtained from subjects with periodontitis, with and without RA, as well as to predict biomarkers, of bacterial pathogens and/or inflammatory mediators, for classification of samples associated with periodontitis and RA.MethodsSalivary samples were obtained from 53 patients with periodontitis and RA and 48 non-RA with chronic periodontitis. The microbial composition was identified using 16S rRNA gene sequencing and compared across periodontitis patients with and without RA. Levels of inflammatory mediators were determined using a multiplex bead assay, compared between the groups and correlated to the microbial profile. The achieved data was analysed using PCoA, DESeq2 and two machine learning algorithms, OPLS-DA and sPLS-DA.ResultsDifferential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC >20) amplicon sequence variants (ASVs) in the non-RA periodontitis group included Alloprevotella sp., Prevotella sp., Haemophilus sp., and Actinomyces sp. whereas Granulicatella sp., Veillonella sp., Megasphaera sp., and Fusobacterium nucleatum were the most highly enriched ASVs (log2 FC >20) in the RA group. OPLS-DA with log2 FC analyses demonstrated that the top ASVs with the highest importance included Vampirovibrio sp. having a positive correlation with non-RA group, and seven ASVs belonging to Sphingomonas insulae, Sphingobium sp., Novosphingobium aromaticivorans, Delftia acidovorans, Aquabacterium spp. and Sphingomonas echinoides with a positive correlation with RA group. Among the detected inflammatory mediators in saliva samples, TWEAK/TNFSF12, IL-35, IFN-α2, pentraxin-3, gp130/sIL6Rb, sIL-6Ra, IL-19 and sTNF-R1 were found to be significantly increased in patients with periodontitis and RA compared to non-RA group with periodontitis. Moreover, correlations between ASVs and inflammatory mediators using sPLS-DA analysis revealed that TWEAK/TNFSF12, pentraxin-3 and IL-19 were positively correlated with the ASVs Sphingobium sp., Acidovorax delafieldii, Novosphingobium sp., and Aquabacterium sp.ConclusionOur results suggest that the combination of microbes and host inflammatory mediators could be more efficient to be used as a predictable biomarker associated with periodontitis and RA, as compared to microbes and inflammatory mediators alone.

Project description:Inflammation is a driven force in modulating microbial communities, but little is known about the interplay between colonizing microorganisms and the immune response in periodontitis. Since local and systemic inflammation may play a whole role in disease, we aimed to evaluate the oral and fecal microbiome of patients with periodontitis and to correlate the oral microbiome data with levels of inflammatory mediator in saliva. Methods: Nine patients with periodontitis (P) in Stage 3/Grade B and nine age-matched non-affected controls (H) were evaluated. Microbial communities of oral biofilms (the supra and subgingival from affected and non-affected sites) and feces were determined by sequencing analysis of the 16SrRNA V3-V4 region. Salivary levels of 40 chemokines and cytokines were correlated with oral microbiome data. Results: Supragingival microbial communities of P differed from H (Pielou's evenness index, and Beta diversity, and weighted UniFrac), since relative abundance (RA) of Defluviitaleaceae, Desulfobulbaceae, Mycoplasmataceae, Peptostreococcales-Tissierellales, and Campylobacteraceae was higher in P, whereas Muribaculaceae and Streptococcaceae were more abundant in H. Subgingival non-affected sites of P did not differ from H, except for a lower abundance of Gemellaceae. The microbiome of affected periodontitis sites (PD ≥ 4 mm) clustered apart from the subgingival sites of H. Oral pathobionts was more abundant in sub and supragingival biofilms of P than H. Fecal samples of P were enriched with Acidaminococcus, Clostridium, Lactobacillus, Bifidobacterium, Megasphaera, and Romboutsia when compared to H. The salivary levels of interleukin 6 (IL-6) and inflammatory chemokines were positively correlated with the RA of several recognized and putative pathobionts, whereas the RA of beneficial species, such as Rothia aeria and Haemophilus parainfluenzae was negatively correlated with the levels of Chemokine C-C motif Ligand 2 (CCL2), which is considered protective. Dysbiosis in patients with periodontitis was not restricted to periodontal pockets but was also seen in the supragingival and subgingival non-affected sites and feces. Subgingival dysbiosis revealed microbial signatures characteristic of different immune profiles, suggesting a role for candidate pathogens and beneficial organisms in the inflammatory process of periodontitis.

Project description:ObjectivePeriodontal disease has been associated with pregnancy complications including preeclampsia. This bioinformatic study is aimed at investigating the possible role of circulating microRNAs (miRNAs) as mediators of the association between maternal periodontal disease and preeclampsia.MethodsPeripheral blood miRNA profiles of periodontitis and controls were sought from Gene Expression Omnibus (GEO), and differential expression analysis was performed. Experimentally validated circulating miRNAs associated with preeclampsia were determined from the Human MicroRNA Disease Database (HMDD v3.0). Venn diagrams were drawn to identify shared circulating differential miRNAs (DEmiRNAs). Significantly enriched target genes, KEGG pathways, and Gene Ontology (GO) terms for the set of shared DEmiRNA were predicted using miRNA enrichment analysis and annotation tool (miEAA v 2.0). Additionally, the shared DEmiRNA-enriched target genes were analyzed for enriched WikiPathways, BioCarta metabolic pathways, and tissue proteins in the human proteome map.ResultsAmong 183 circulating DEmiRNA in periodontitis and 60 experimentally validated miRNA in preeclampsia, 9 shared DEmiRNA were identified. The top among 32 overrepresented target genes included MAFB, PSAP, and CDK5RAP2, top among 14 enriched KEGG pathways were renin-angiotensin system and graft-versus-host disease, and that among enriched 44 GO profiles included "positive regulation of epidermal growth factor-activated receptor activity" and "sequestering of calcium ion." In the overrepresented target gene set, among 10 enriched WikiPathways, the top included "NAD metabolism, sirtuins, and aging" and "regulation of Wnt/B-catenin signaling by small molecule compounds" and PPAR-related mechanisms was top among 13 enriched BioCarta metabolic pathways.ConclusionA circulating 9-DEmiRNA set was significantly linked to both periodontitis and preeclampsia. Enrichment analysis identified specific genes, pathways, and functional mechanisms, which may be epigenetically altered and thereby mediate the biological association of periodontitis and preeclampsia.

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Identification of Salivary Microbiota and Its Association With Host Inflammatory Mediators in Periodontitis.

Publications

Identification of Salivary Microbiota and Its Association With Host Inflammatory Mediators in Periodontitis.

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