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Objective: To identify gingival crevicular fluid (GCF)‐derived inflammatory markers of periodontitis progression and periodontal treatment impact. Methods: Periodontally healthy (H; n = 112) and periodontitis (P; n = 302) patients were monitored bi‐monthly for 1 year without therapy. Periodontitis patients were re‐examined 6 months after non‐surgical periodontal therapy (NSPT). Levels of 64 biomarkers were measured in the GCF samples collected at each visit from progressing (n = 12 sites in H; n = 76 in P) and stable (n = 100 in H, n = 225 in P) sites. Clinical parameters and log‐transformed analyte levels were averaged within clinical groups at each time point and analysed using linear mixed models. Results: During monitoring, progressing sites had significantly higher levels of IL‐1β, MMP‐8, IL‐12p40, EGF and VEGF. MMP‐9 and Periostin were significantly more elevated in stable sites. Distinct cytokine profiles were observed based on baseline PD. Treatment led to significant reductions in Eotaxin, Flt‐3L, GDF‐15, GM‐CSF, IL‐1β, IL‐17, MIP‐1d, RANTES and sCD40L, and increases in IP‐10 and MMP‐9. Conclusion: Distinct cytokine signatures observed in stable and progressing sites were maintained over time in the absence of treatment and significantly affected by NSPT. [ABSTRACT FROM AUTHOR]

Aim: To identify serum‐ and salivary‐derived inflammatory biomarkers of periodontitis progression and determine their response to non‐surgical treatment. Materials and Methods: Periodontally healthy (H; n = 113) and periodontitis patients (P; n = 302) were monitored bi‐monthly for 1 year without therapy. Periodontitis patients were re‐examined 6 months after non‐surgical periodontal therapy (NSPT). Participants were classified according to disease progression: P0 (no sites progressed; P1: 1–2 sites progressed; P2: 3 or more sites progressed). Ten salivary and five serum biomarkers were measured using Luminex. Log‐transformed levels were compared over time according to baseline diagnosis, progression trajectory and after NSPT. Significant differences were sought using linear mixed models. Results: P2 presented higher levels (p <.05) of salivary IFNγ, IL‐6, VEGF, IL‐1β, MMP‐8, IL‐10 and OPG over time. Serum analytes were not associated with progression. NSPT led to clinical improvement and significant reduction of IFNγ, IL‐6, IL‐8, IL‐1β, MMP‐8, IL‐10, OPG and MMP‐9 in saliva and of CRP, MMP‐8, MMP‐9 and MPO in serum. Conclusions: Periodontitis progression results from a sustained pro‐inflammatory milieu that is reflected in salivary biomarkers, but less so in serum, likely because of the limited amount of progression per patient. NSPT can significantly decrease the levels of several salivary analytes. [ABSTRACT FROM AUTHOR]

Aims: To explore the influence of gender on periodontal treatment outcomes in a dataset of eight RCTs conducted in Brazil, United States, and Germany. Methods: Clinical parameters were compared between men and women with stages III/IV grades B/C generalized periodontitis at baseline and 1‐year post‐therapy, including scaling and root planing with or without antibiotics. Results: Data from 1042 patients were analyzed. Men presented a tendency towards higher probing depth (p =.07, effect size = 0.11) and clinical attachment level (CAL) than women at baseline (p =.01, effect size = 0.16). Males also presented statistically significantly lower CAL gain at sites with CAL of 4–6 mm at 1‐year post‐therapy (p =.001, effect size = 0.20). Among patients with Grade B periodontitis who took antibiotics, a higher frequency of women achieved the endpoint for treatment (i.e., ≤4 sites PD ≥5 mm) at 1 year than men (p <.05, effect size = 0.12). Conclusion: Men enrolled in RCTs showed a slightly inferior clinical response to periodontal therapy in a limited number of sub‐analyses when compared to women. These small differences did not appear to be clinically relevant. Although gender did not dictate the clinical response to periodontal treatment in this population, our findings suggest that future research should continue to explore this topic. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insights on the link between periodontal disease and lung cancer. Methods: In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls. We examined the association between 37 DNA-methylated 5'--C--phosphate--G--3' (CpG) sites at three genomic regions, homeobox 4 (HOXA4), zinc finger protein (ZFP57), and a long noncoding RNA gene located in Chr10 (ENSG00000231601), and lung cancer risk. Results: Statistically significant associations with lung cancer risk were observed for all 14 CpG sites from HOXA4 (OR ranging 1.41-1.62 for 1 SD increase in the DNA methylation level, especially within 15 years) and 1 CpG site on gene ENSG00000231601 (OR = 1.34 for 1 SD increase in the DNA methylation level). Although CpG sites on gene ZFP57 were not associated with lung cancer risk overall, statistically significant inverse associations were noted for six CpG sites when restricting follow-up to 15 years (OR = 0.73-0.77 for 1 SD increase in the DNA methylation level). Conclusions: Key methylation levels associated with periodontal disease are also associated with lung cancer risk. For both HOXA4 and ZFP57, the associations were stronger within 15 years of follow-up, which suggest that, if causal, the impact of methylation is acting late in the natural history of lung cancer. [ABSTRACT FROM AUTHOR]

Background: Dental caries is a microbe and sugar-mediated biofilm-dependent oral disease. Of particular significance, a virulent type of dental caries, known as severe early childhood caries (S-ECC), is characterized by the synergistic polymicrobial interaction between the cariogenic bacterium, Streptococcus mutans, and an opportunistic fungal pathogen, Candida albicans. Although cross-sectional studies reveal their important roles in caries development, these exhibit limitations in determining the significance of these microbial interactions in the pathogenesis of the disease. Thus, it remains unclear the mechanism(s) through which the cross-kingdom interaction modulates the composition of the plaque microbiome. Here, we employed a novel ex vivo saliva-derived microcosm biofilm model to assess how exogenous pathogens could impact the structural and functional characteristics of the indigenous native oral microbiota. Results: Through shotgun whole metagenome sequencing, we observed that saliva-derived biofilm has decreased richness and diversity but increased sugar-related metabolism relative to the planktonic phase. Addition of S. mutans and/or C. albicans to the native microbiome drove significant changes in its bacterial composition. In addition, the effect of the exogenous pathogens on microbiome diversity and taxonomic abundances varied depending on the sugar type. While the addition of S. mutans induced a broader effect on Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog abundances with glucose/fructose, S. mutans-C. albicans combination under sucrose conditions triggered unique and specific changes in microbiota composition/diversity as well as specific effects on KEGG pathways. Finally, we observed the presence of human epithelial cells within the biofilms via confocal microscopy imaging. Conclusions: Our data revealed that the presence of S. mutans and C. albicans, alone or in combination, as well as the addition of different sugars, induced unique alterations in both the composition and functional attributes of the biofilms. In particular, the combination of S. mutans and C. albicans seemed to drive the development (and perhaps the severity) of a dysbiotic/cariogenic oral microbiome. Our work provides a unique and pragmatic biofilm model for investigating the functional microbiome in health and disease as well as developing strategies to modulate the microbiome. 7vqKFKr_A75FzMGKU9ihFH Video Abstract [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of scaling and root planing (SRP) on the dynamics of gene expression by the host and the microbiome in subgingival plaque samples. Materials and Methods: Fourteen periodontitis patients were closely monitored in the absence of periodontal treatment for 12 months. During this period, comprehensive periodontal examination and subgingival biofilm sample collection were performed bi‐monthly. After 12 months, clinical attachment level (CAL) data were compiled and analysed using linear mixed models (LMM) fitted to longitudinal CAL measurements for each tooth site. LMM classified the sites as stable (S), progressing (P), or fluctuating (F). After the 12‐month visit, subjects received SRP, and at 15 months they received comprehensive examination and supportive periodontal therapy. Those procedures were repeated at the 18‐month visit, when patients were also sampled. Each patient contributed with one S, one P, and one F site collected at the 12‐ and 18‐month visits. Samples were analysed using Dual RNA‐Sequencing to capture host and bacterial transcriptomes simultaneously. Results: Microbiome and host response behaviour were specific to the site's progression classification (i.e., S, P, or F). Microbial profiles of pre‐ and post‐treatment samples exhibited specific microbiome changes, with progressing sites showing the most significant changes. Among them, Porphyromonas gingivalis was reduced after treatment, while Fusobacterium nucleatum showed an increase in proportion. Transcriptome analysis of the host response showed that interleukin (IL)‐17, TNF signalling pathways, and neutrophil extracellular trap formation were the primary immune response activities impacted by periodontal treatment. Conclusions: SRP resulted in a significant "rewiring" of host and microbial activities in the progressing sites, while restructuring of the microbiome was minor in stable and fluctuating sites. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, to date, no studies have comprehensively assessed the changes occurring in the subgingival microbiome of young patients with periodontitis treated by means of mechanical and antibiotic therapy. Thus, this study aimed to use next-generation sequencing to evaluate the subgingival microbial composition of young patients with severe periodontitis treated with scaling and root planing and systemic metronidazole and amoxicillin.Methods: Subgingival samples from healthy individuals and shallow and deep sites from periodontitis patients were individually collected at baseline and 90 days post-treatment. The samples were analyzed using 16S rRNA-gene sequencing (MiSeq-Illumina) and QIIME pipeline. Differences between groups for the microbiological data were determined using principal coordinate analysis (PCoA), linear mixed models, and the PERMANOVA test.Results: One hundred samples were collected from 10 periodontitis patients and seven healthy individuals. PCoA analysis revealed significant partitioning between pre-and post-treatment samples. No major differences in the composition of the subgingival microbiota were observed between shallow and deep sites, at baseline or at 90-days post-treatment, and the microbiome of both site categories after treatment moved closer in similarity to that observed in periodontal health. Treatment significantly improved all clinical parameters and reduced the relative abundance of classical periodontal pathogens and of Fretibacterium fastidiosum, Eubacterium saphenum, Porphyromonas endodontalis, Treponema medium, Synergistetes, TM7, and Treponema spp, and increased that of Actinomyces, Rothia, Haemophilus, Corynebacterium, and Streptococci spp.Conclusion: Mechanical treatment associated with metronidazole and amoxicillin promoted a beneficial change in the microbiome of young individuals with severe periodontitis. [ABSTRACT FROM AUTHOR]

Since 2010, next-generation sequencing platforms have laid the foundation to an exciting phase of discovery in oral microbiology as it relates to oral and systemic health and disease. Next-generation sequencing has allowed large-scale oral microbial surveys, based on informative marker genes, such as 16S ribosomal RNA, community gene inventories (metagenomics), and functional analyses (metatranscriptomics), to be undertaken. More specifically, the availability of next-generation sequencing has also paved the way for studying, in greater depth and breadth, the effect of systemic factors on the periodontal microbiome. It was natural to investigate systemic diseases, such as diabetes, in such studies, along with systemic conditions or states, , pregnancy, menopause, stress, rheumatoid arthritis, and systemic lupus erythematosus. In addition, in recent years, the relevance of systemic "variables" (ie, factors that are not necessarily diseases or conditions, but may modulate the periodontal microbiome) has been explored in detail. These include ethnicity and genetics. In the present manuscript, we describe and elaborate on the new and confirmatory findings unveiled by next-generation sequencing as it pertains to systemic factors that may shape the periodontal microbiome. We also explore the systemic and mechanistic basis for such modulation and highlight the importance of those relationships in the management and treatment of patients. [ABSTRACT FROM AUTHOR]

The starting point for defining effective treatment protocols is a clear understanding of the etiology and pathogenesis of a condition. In periodontal diseases, this understanding has been hindered by a number of factors, such as the difficulty in differentiating primary pathogens from nonpathogens in complex biofilm structures. The introduction of DNA sequencing technologies, including taxonomic and functional analyses, has allowed the oral microbiome to be investigated in much greater breadth and depth. This article aims to compile the results of studies, using next-generation sequencing techniques to evaluate the periodontal microbiome, in an attempt to determine how far the knowledge provided by these studies has brought us in terms of influencing the way we treat periodontitis. The taxonomic data provided, to date, by published association and elimination studies using next-generation sequencing confirm previous knowledge on the role of classic periodontal pathogens in the pathobiology of disease and include new species/genera. Conversely, species and genera already considered as host-compatible and others less explored were associated with periodontal health as their levels were elevated in healthy individuals and increased after therapy. Functional and transcriptomic analyses also demonstrated that periodontal biofilms are taxonomically diverse, functionally congruent, and highly cooperative. Very few interventional studies to date have examined the effects of treatment on the periodontal microbiome, and such studies are heterogeneous in terms of design, sample size, sampling method, treatment provided, and duration of follow-up. Hence, it is still difficult to draw meaningful conclusions from them. Thus, although OMICS knowledge has not yet changed the way we treat patients in daily practice, the information provided by these studies opens new avenues for future research in this field. As new pathogens and beneficial species become identified, future randomized clinical trials could monitor these species/genera more comprehensively. In addition, the metatranscriptomic data, although still embryonic, suggest that the interplay between the host and the oral microbiome may be our best opportunity to implement personalized periodontal treatments. Therapeutic schemes targeting particular bacterial protein products in subjects with specific genetic profiles, for example, may be the futuristic view of enhanced periodontal therapy. [ABSTRACT FROM AUTHOR]

A better characterization of the peri-implant microbiome can improve the understanding of the etiology of peri-implant diseases. Ultimately, more detailed information about the peri-implantitis microbiome will lead to better strategies for prevention, supportive therapy, and risk assessment, as well as early diagnosis of peri-implantitis and timely intervention, all of which are critical for the long-term retention of implants. [ABSTRACT FROM AUTHOR]