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Introducción: la percepción de la salud es un predictor significativo de mortalidad, de actitudes hacia la muerte y de cumplimiento de tratamientos durante la enfermedad; cómo se observan las personas en bienestar físico actual, futuro y adaptación psicológica; por tanto, tiene un papel importante en la conducta promotora de salud. Lo descrito motivó la reflexión sobre esos conceptos y la actuación de los pacientes con diabetesmellitus tipo 2 (PDMT2), enfermedad que representa un problema de salud pública mundial. Propósito: determinar el efecto de los factores personales (biológicos, psicológicos y socioculturales) sobre el resultado de conducta (estilo de vida) de los pacientes con diabetes mellitus tipo 2. Marco teórico: “Modelo de promoción de la salud” de Pender (1). Metodología: diseño descriptivo-correlacional, en una muestra de 125 pacientes. Resultados: la variable factores personales mostró efecto sobre la variable estilo de vida (nutrición, ejercicio, responsabilidad en salud y manejo adecuado del estrés) (F cal = 4.780 R2 38,7, p = ,001). Conclusión: los resultados apoyan la relación entre los conceptos seleccionados del “Modelo de promoción de la salud” de Pender (2003) y muestran que la percepción de salud de los PDMT2 promueve cambios de la conducta promotora (estilo de vida), por lo que se cree que los pacientes pueden actuar, corresponsablemente con el equipo de salud, para mejorar el control del padecimiento y evitar o retrasar complicaciones.Introduction: Perceived Health is a significant predictor of mortality, attitude towards death, adherence to treatments during illnesses; i.e. the way people see themselves in their current and future condition and in their psychological adaptation to it. Therefore, it plays an important role on health promoting behavior. This study made us ponder about these concepts and about habits of patients with type 2 diabetes mellitus (PDMT2), which represents a global health problem. Purpose: to determine the effect of personal conditions (biological, psychological and social-cultural) over the behavior (life style) of patients with type 2 diabetes mellitus. Theoretical Framework: “Pender’s health promotion model” (1). Methodology: descriptive-co-relational design in a sample of 125 patients. Results: the personal condition variables (biological, psychological and social-cultural) had an impact on the lifestyle variable (nutrition, exercise, health related responsibility and appropriate stress management) (F cal, = 4.780 R2 38,7, p = 0,001). Conclusion: results support the relationship between concepts selected from “Pender’s health promotion model” (2003) and those that show that health perception of PDMT2 promotes changes in motor behavior (i.e. in lifestyle). Therefore, patients are able to act, in co-responsibility with the health team, to improve control of their illness and to avoid or to delay complications.Introdução: a saúde pode predizer a mortalidade, bem como as atitudes a respeito da morte, a adesão aos tratamentos durante a doença, a forma como as pessoas se observam em bem-estar físico atual, futuro e a adaptação psicológica. Portanto, a saúde tem um papel importante na conduta voltada à promoção da saúde. O descrito anteriormente levantou a reflexão sobre esses conceitos e sobre a atuação dos pacientes com diabetes tipo 2, doença que representa um problema de saúde pública mundial. Objetivo: determinar o efeito dos fatores pessoais (biológicos, psicológicos e sócio-culturais) no resultado de conduta (estilo de vida) dos pacientes com diabetes mellitus tipo 2 (PDMT2). Bases teóricas: “Modelo de promoção da saúde de Pender” (1). Metodologia: análise descritivo – correlacional, numa amostra de 125 pacientes. Resultados: a variável de fatores pessoais (biológicos, psicológicos y sócio-culturais) mostrou efeitos na variável estilo de vida (nutrição, exercício físico, responsabilidade com a saúde e gestão adequada do estresses) (F cal, = 4.780 R2 38,7, p = 0,001). Conclusão: os resultados demonstram a relação entre os conceitos selecionados do “Modelo de promoção da saúde” de Pender (2003) e provam que a promoção da saúde nos PDMT2 determina mudanças da conduta (estilo de vida). Por esta razão se considera que os PDMT2 podem agir, junto com sua equipe médica, para melhorar o controle da doença evitando ou retardando o aparecimento de complicações.

Fue el Dr. Fernández miembro destacado de la comunidad botánica latinoamericana formada hacia la mitad del siglo, y en Colombia desempeñó un papel importante como miembro de planta del Herbario Nacional Colombiano y del Instituto de Ciencias Naturales de la Facultad de Ciencias de la Universidad Nacional de Colombia. Nació el Dr. Fernández el 11 de febrero de 1920 en la procera ciudad de Popayán, donde tras adelantar los estudios primarios y secundarios obtuvo en 1940 el título de bachiller en el Liceo de la Universidad del Cauca; cumplida esta etapa se desplazó a Bogotá, ingresando a la Universidad Nacional donde completó el plan de estudios de la carrera de Farmacia e inició el curso del doctorado que se ofrecía para la época.

El epíteto específico alude al nombre vernáculo "Gorrelana" (deformación de las palabras gorro de lana) dado por los pobladores de la vereda Chaguacá a esta especie, hasta ahora conocida como uno de los elementos de las consociaciones de Robles (Quercetum) de la Cordillera Oriental de Colombia.Agradezco al profesor Lorenzo Uribe por la revisión de la diagnosis latina y al señor Silvio Fernández por su esmero al ilustrar la especie.

Se presenta tanto en forma numérica como alfabética, una completa relación de las Compositae del Herbario de J. C. MUTIS depositado en el Real Jardín Botánico de Madrid (MA) y se señalan los ejemplares duplicados en el Herbario Nacional Colombiano (COL) y en United States National Herbarium (US). Se acompaña esta relación con datos históricos relativos a las colecciones realizadas en desarrollo de la Expedición.En el Real Jardín Botánico de Madrid (MA) y bajo el nombre de "Plantae Expeditionis Botanicae Mutisii Vice - Regni Novae - Granatae (1783-1808) ", se encuentra depositada la mayor parte de las colecciones botánicas realizadas por JOSÉ CELESTINO MUTIS y por sus colaboradores en desarrollo de la célebre Expedición Botánica, Esta colecció agrupa no sólo el herbario del propio MUTIS, sino que incluye los herbarios de FRANCISCO JOSE DE CALDAS (herborizaciones hechas en el Sur de Colombia y en Ecuador), SINFOROSO MUTIS CONSUEGRA (herborizaciones llevadas a cabo en los alrededores de Bogotá y algunas colecciones hechas en Cuba), JUAN ELOY VALENZUELA (herborizaciones principalmente realizadas en Boyacá y Santander) y demás adjuntos de la Expedición. Estos materiales, junto con la colección iconográfica, gran parte de los manuscritos, correspondencia y demás colecciones, fueron remitidos a España en 1816 durante el período de reconquista del Virreinato.Una vez en Madrid, los materiales relativos a la labor botánica pasaron a custodia del Jardín. En el curso de 170 años, parte de ellos han sufrido la acción del tiempo, los elementos y los microorganismos, pero en su conjunto se conservan en estado satistactorio.

Espeletia guacharaca Díaz, sp. nov. / Caulirrosuletum / Typus / Aquenios / Isotypus / Paratypi

Bajo este título se han publicado varios artículos en los cuales se han propuesto nuevas especies de asteráceas de los géneros Espeletia, Paragynoxys, Senecio y Verbesina; en esta ocasión se describe una especie de Senecio, novedad surgida en desarrollo de la revisión del material de herbario y preparación de los textos del tratamiento de las Cornpositae de la Flora de la Real Expedición Botánica del Nuevo Reino de Granada. Se trata de una interesante especie sobresaliente por el color blanco de las flores femeninas y de la cual se conservan en los archivos del Real Jardín Botánico de Madrid, una bella lámina iluminada en color y una diagnosis.

Eighty-six chromosome counts of Compositae are reported from differentprovinces of Colombia. Twenty-four are first counts from the genusPlagiocheilus (Astereae), and from species in Achyrocline, Aspilia, Baccharis, Calea, Eupatorium, Hieracium, Liabum, T agetes, Verbesina, Vernonia and We delia. Additional counts are also provided for 62 populations of taxa counted previously of which nine are new numbers. The systematic significance of certain of these counts is discussed.Se proporciona información acerca de ochenta y seis recuentos cromosómicos de Compositae de varias regiones de Colombia.Veinticuatro recuentos corresponden a los primeros resultados citológicos para el género Plagiocbeilus (Astereae), y para especies de Aclryrocltne, Aspilia, Baccharis, Calea, Eupatorium, Hieracium, Liabum, Tagetes, Verbesina y Wedelia. Se mencionan también recuentos en sesenta y dos poblaciones de taxa investigados anteriormente, de las cuales nueve corresponden a nuevos números, Se menciona la importancia sistemática de algunos de los nuevos recuentos.

Rafael Romero Castañeda / Andrés Soriano Lleras.

Background: Dietary intake has been suggested to be associated with the oral microbiome, but no study has examined the association between overall diet quality and the oral microbiome., Objectives: This study aimed to investigate the cross-sectional association between the Healthy Eating Index-2020 (HEI-2020) and the diversity and composition of the oral microbiome among participants in the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) Study., Methods: In 1175 postmenopausal women (mean age: 67 ± 7.0 y), we estimated the HEI-2020 scores for each woman from a food frequency questionnaire administered from 1997 to 2000. Bacterial DNA was extracted from subgingival plaque samples and analyzed using 16S ribosomal RNA sequencing. The alpha-diversity (within-sample diversity) and β-diversity (between-sample diversity) across HEI-2020 quartiles were examined using analysis of covariance and permutational multivariate analysis of variance, respectively. The associations between the HEI-2020 score and the relative abundance of microbial taxa were examined by linear regression models. The analyses were further conducted for individual components of the HEI-2020., Results: No statistically significant associations were observed between the HEI-2020 scores and alpha- or beta-diversity. However, greater consumption of seafood, plant proteins, and total protein and lower consumption of added sugars were positively associated with alpha-diversity. After we applied a false detection rate (FDR) correction, higher HEI-2020 scores were significantly associated with decreased abundance of Lautropia, Streptococcus gordonii, Cardiobacterium valvarum, and Cardiobacterium hominis, and increased abundance of Selenomonas sp. oral taxon 133 and Selenomonas dianae (FDR-adjusted P values < 0.10). Additionally, 28 other taxa were identified as being associated with HEI-2020 components., Conclusions: Although the HEI-2020 was associated with the composition, but not the diversity, of the oral microbiome, individual HEI-2020 components were associated with both its diversity and composition. Specific dietary components may have more impact on the diversity and composition of oral microbiome than overall diet quality assessed by the HEI-2020., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Many chronic inflammatory diseases are attributed to disturbances in host-microbe interactions, which drive immune-mediated tissue damage. Depending on the anatomic setting, a chronic inflammatory disease can exert unique local and systemic influences, which provide an exceptional opportunity for understanding disease mechanism and testing therapeutic interventions. The oral cavity is an easily accessible environment that allows for protective interventions aiming at modulating the immune response to control disease processes driven by a breakdown of host-microbe homeostasis. Periodontal disease (PD) is a prevalent condition in which quantitative and qualitative changes of the oral microbiota (dysbiosis) trigger nonresolving chronic inflammation, progressive bone loss, and ultimately tooth loss. Here, we demonstrate the therapeutic benefit of local sustained delivery of the myeloid-recruiting chemokine (C-C motif) ligand 2 (CCL2) in murine ligature-induced PD using clinically relevant models as a preventive, interventional, or reparative therapy. Local delivery of CCL2 into the periodontium inhibited bone loss and accelerated bone gain that could be ascribed to reduced osteoclasts numbers. CCL2 treatment up-regulated M2-macrophage and downregulated proinflammatory and pro-osteoclastic markers. Furthermore, single-cell ribonucleic acid (RNA) sequencing indicated that CCL2 therapy reversed disease-associated transcriptomic profiles of murine gingival macrophages via inhibiting the triggering receptor expressed on myeloid cells-1 (TREM-1) signaling in classically activated macrophages and inducing protein kinase A (PKA) signaling in infiltrating macrophages. Finally, 16S ribosomal ribonucleic acid (rRNA) sequencing showed mitigation of microbial dysbiosis in the periodontium that correlated with a reduction in microbial load in CCL2-treated mice. This study reveals a novel protective effect of CCL2 local delivery in PD as a model for chronic inflammatory diseases caused by a disturbance in host-microbe homeostasis., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: The aim of the present study was to evaluate the subgingival microbiome in patients with grade C molar-incisor pattern periodontitis (C-MIP) affecting the primary or permanent dentitions., Methods: DNA was isolated from subgingival biofilm samples from diseased and healthy sites from 45 C-MIP patients and subjected to phylogenetic microarray analysis. C-MIP sites were compared between children affected in the primary to those affected in the permanent dentitions. Within-subject differences between C-MIP-affected sites and dentition-matched healthy sites were also evaluated., Results: C-MIP sites of subjects affected in the primary dentition showed partially overlapping but distinct microbial communities from C-MIP permanent dentition sites (p < 0.05). Differences were due to increased levels in primary C-MIP sites of certain species of the genera Capnocytophaga and Leptotrichia, while C-MIP permanent dentition sites showed higher prevalence of Filifactor alocis. Aggregatibacter actinomycetemcomitans (Aa) was among species seen in high prevalence and levels in both primary and permanent C-MIP sites. Moreover, both permanent and primary C-MIP sites showed distinct microbial communities when compared to dentition-matched healthy sites in the same subject (p < 0.01)., Conclusions: Primary and permanent teeth with C-MIP showed a dysbiotic microbiome, with children affected in the primary dentition showing a distinct profile from those affected in the permanent dentition. However, Aa was enriched in both primary and permanent diseased sites, confirming that this microorganism is implicated in C-MIP in both dentitions., (© 2024 American Academy of Periodontology.)

At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The control of dental biofilm regrowth after nonsurgical periodontal therapy is associated with better clinical outcomes. However, many patients have difficulty achieving optimal plaque control. Subjects with diabetes, in which immune and wound-healing responses are typically impaired, may benefit from intensive antiplaque control regimens after scaling and root planing (SRP)., Objectives: This study aimed to evaluate the effects of an intensive, at-home, chemical, and mechanical antiplaque regimen as an adjunct to SRP for the treatment of moderate to severe periodontitis. A secondary objective was to compare responses in subjects with type 2 diabetes and nondiabetics., Methods: This was a 6-mo, single-center, parallel-group, randomized trial. The test group received SRP and oral hygiene instructions, and subjects were instructed to use a 0.12% chlorhexidine gluconate mouthrinse twice a day for 3 mo and utilize rubber interproximal bristle cleaners twice a day for 6 mo. The control group received SRP and oral hygiene instructions. The main outcome was change in mean probing depth (PD) from baseline to 6 mo. Secondary outcomes included change in sites with deep PDs, mean clinical attachment level, bleeding on probing, plaque index, hemoglobin A1C, fasting blood glucose, C-reactive protein, and taste assessment. This study was registered at ClinicalTrials.gov as NCT04830969., Results: In total, 114 subjects were randomized to either treatment. Eighty-six subjects completed the trial with no missing visits. Neither an intention-to-treat nor a per-protocol analysis showed statistically significant differences between treatment groups in mean PD at 6 mo. In a subgroup analysis, subjects with diabetes in the test group showed a statistically significant greater reduction in mean PD at 6 mo when compared to subjects with diabetes receiving the control treatment (Δ = 0.15, P = 0.04), while there were no differences within nondiabetics (Δ = 0.02, P = 0.75)., Conclusion: Outcomes in subjects with diabetes may be improved by chemo-mechanical antiplaque measures after nonsurgical periodontal therapy., Knowledge Transfer Statement: This study suggests diabetic subjects may benefit from an intensive, at-home, chemical, and mechanical antiplaque regimen to improve nonsurgical periodontal therapy outcomes., Competing Interests: Declaration of Conflicting InterestsThis study was funded by Sunstar, Inc. who manufactures Paroex and Soft-Picks. Sunstar employees who are coauthors in this manuscript participated in the study design but did not participate in data analysis or manuscript writing.

Porphyromonas gingivalis, a Gram-negative anaerobic bacterium commonly found in human subgingival plaque, is a major etiologic agent for periodontitis and has been associated with multiple systemic pathologies. Many P. gingivalis strains have been identified and different strains possess different virulence factors. Current oral microbiome approaches (16S or shotgun) have been unable to differentiate P. gingivalis strains. This study presents a new approach that aims to improve the accuracy of strain identification, using a detection method based on sequencing of the intergenic spacer region (ISR) which is variable between P. gingivalis strains. Our approach uses two-step PCR to amplify only the P. gingivalis ISR region. Samples are then sequenced with an Illumina sequencer and mapped to specific strains. Our approach was validated by examining subgingival plaque from 153 participants with and without periodontal disease. We identified the avirulent strain ATCC33277/381 as the most abundant strain across all sample types. The W83/W50 strain was significantly enriched in periodontitis, with 13% of participants harboring that strain. Overall, this approach can have significant implications not only for the diagnosis and treatment of periodontal disease but also for other diseases where P. gingivalis or its toxins have been implicated, such as Alzheimer's disease., (© 2024. The Author(s).)

Neutrophil infiltration is a hallmark of periodontitis, a prevalent oral inflammatory condition in which Th17-driven mucosal inflammation leads to destruction of tooth-supporting bone. Herein, we document that neutrophil extracellular traps (NETs) are early triggers of pathogenic inflammation in periodontitis. In an established animal model, we demonstrate that neutrophils infiltrate the gingival oral mucosa at early time points after disease induction and expel NETs to trigger mucosal inflammation and bone destruction in vivo. Investigating mechanisms by which NETs drive inflammatory bone loss, we find that extracellular histones, a major component of NETs, trigger upregulation of IL-17/Th17 responses, and bone destruction. Importantly, human findings corroborate our experimental work. We document significantly increased levels of NET complexes and extracellular histones bearing classic NET-associated posttranslational modifications, in blood and local lesions of severe periodontitis patients, in the absence of confounding disease. Our findings suggest a feed-forward loop in which NETs trigger IL-17 immunity to promote immunopathology in a prevalent human inflammatory disease., (© 2023 Moutsopoulos et al.)

Intestinal colonization of the oral bacterium Haemophilus parainfluenzae has been associated with Crohn's disease (CD) severity and progression. This study examines the role of periodontal disease (PD) as a modifier for colonization of H. parainfluenzae in patients with CD and explores the mechanisms behind H. parainfluenzae-mediated intestinal inflammation. Fifty subjects with and without CD were evaluated for the presence of PD, and their oral and fecal microbiomes were characterized. PD is associated with increased levels of H. parainfluenzae strains in subjects with CD. Oral inoculation of H. parainfluenzae elicits strain-dependent intestinal inflammation in murine models of inflammatory bowel disease, which is associated with increased intestinal interferon-γ (IFN-γ)+ CD4+ T cells and disruption of the host hypusination pathway. In summary, this study establishes a strain-specific pathogenic role of H. parainfluenzae in intestinal inflammation and highlights the potential effect of PD on intestinal colonization by pathogenic H. parainfluenzae strains in patients with CD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study investigated the association between menopausal hormone therapy (HT) use and the subgingival microbiome, for which published information is limited., Methods: This cross-sectional study included 1270 postmenopausal women, aged 53-81 years, who completed clinical examinations. Detailed information on HT use (type, delivery mode, duration) was obtained from questionnaires. HT use was categorized into three groups (never, former, current). 16S rRNA sequencing was performed on subgingival plaque samples obtained during dental examinations. Operational taxonomic units were centered log2-ratio (CLR) transformed to account for the compositional data structure. Analysis of variance was used to compare mean microbial relative abundances across HT categories with Benjamini-Hochberg correction., Results: Significantly higher alpha diversity (Shannon Index) and beta diversity (Aitchison distance) was observed in never compared with current HT users (p < 0.05, each). Of the total 245 microbial taxa identified, 18 taxa differed significantly among the three HT groups, 11 of which were higher in current users and seven of which were lower in current users as compared with never users (p < 0.05, each). Differences in relative abundance between never and current HT users were materially unchanged after adjustment for age, body mass index, and oral hygiene., Conclusions: Relative abundance of several subgingival bacteria differed significantly between never and current HT users in a cohort of postmenopausal women. Additional studies are needed to determine the extent that these relationships might account for the previously reported inverse association between HT use and periodontal disease in older women., (© 2022 American Academy of Periodontology.)

A microbial community is a dynamic system undergoing constant change in response to internal and external stimuli. These changes can have significant implications for human health. However, due to the difficulty in obtaining longitudinal samples, the study of the dynamic relationship between the microbiome and human health remains a challenge. Here, we introduce a novel computational strategy that uses massive cross-sectional sample data to model microbiome landscapes associated with chronic disease development. The strategy is based on the rationale that each static sample provides a snapshot of the disease process, and if the number of samples is sufficiently large, the footprints of individual samples populate progression trajectories, which enables us to recover disease progression paths along a microbiome landscape by using computational approaches. To demonstrate the validity of the proposed strategy, we developed a bioinformatics pipeline and applied it to a gut microbiome dataset available from a Crohn's disease study. Our analysis resulted in one of the first working models of microbial progression for Crohn's disease. We performed a series of interrogations to validate the constructed model. Our analysis suggested that the model recapitulated the longitudinal progression of microbial dysbiosis during the known clinical trajectory of Crohn's disease. By overcoming restrictions associated with complex longitudinal sampling, the proposed strategy can provide valuable insights into the role of the microbiome in the pathogenesis of chronic disease and facilitate the shift of the field from descriptive research to mechanistic studies., Competing Interests: The authors have declared that no competing interests exist.

Background: The integrated approach to electrical cardioversion (EC) in atrial fibrillation (AF) is complex; candidates can resolve spontaneously while waiting for EC, and post-cardioversion recurrence is high. Thus, it is especially interesting to avoid the programming of EC in patients who would restore sinus rhythm (SR) spontaneously or present early recurrence. We have analyzed the whole elective EC of the AF process using machine-learning (ML) in order to enable a more realistic and detailed simulation of the patient flow for decision making purposes. Methods: The dataset consisted of electronic health records (EHRs) from 429 consecutive AF patients referred for EC. For analysis of the patient outcome, we considered five pathways according to restoring and maintaining SR: (i) spontaneous SR restoration, (ii) pharmacologic-cardioversion, (iii) direct-current cardioversion, (iv) 6-month AF recurrence, and (v) 6-month rhythm control. We applied ML classifiers for predicting outcomes at each pathway and compared them with the CHA2DS2-VASc and HATCH scores. Results: With the exception of pathway (iii), all ML models achieved improvements in comparison with CHA2DS2-VASc or HATCH scores (p < 0.01). Compared to the most competitive score, the area under the ROC curve (AUC-ROC) was: 0.80 vs. 0.66 for predicting (i); 0.71 vs. 0.55 for (ii); 0.64 vs. 0.52 for (iv); and 0.66 vs. 0.51 for (v). For a threshold considered optimal, the empirical net reclassification index was: +7.8%, +47.2%, +28.2%, and +34.3% in favor of our ML models for predicting outcomes for pathways (i), (ii), (iv), and (v), respectively. As an example tool of generalizability of ML models, we deployed our algorithms in an open-source calculator, where the model would personalize predictions. Conclusions: An ML model improves the accuracy of restoring and maintaining SR predictions over current discriminators. The proposed approach enables a detailed simulation of the patient flow through personalized predictions.

The subgingival crevice harbors diverse microbial communities. Shifts in the composition of these communities occur with the development of gingivitis and periodontitis, which are considered as successive stages of periodontal health deterioration. It is not clear, however, to what extent health- and gingivitis-associated microbiota are protective, or whether these communities facilitate the successive growth of periodontitis-associated taxa. To further our understanding of the dynamics of the microbial stimuli that trigger disruptions in periodontal homeostasis, we reviewed the available literature with the aim of defining specific microbial signatures associated with different stages of periodontal dysbiosis. Although several studies have evaluated the subgingival communities present in different periodontal conditions, we found limited evidence for the direct comparison of communities in health, gingivitis, and periodontitis. Therefore, we aimed to better define subgingival microbiome shifts by merging and reanalyzing, using unified bioinformatic processing strategies, publicly available 16S ribosomal RNA gene amplicon datasets of periodontal health, gingivitis, and periodontitis. Despite inherent methodological differences across studies, distinct community structures were found for health, gingivitis, and periodontitis, demonstrating the specific associations between gingival tissue status and the subgingival microbiome. Consistent with the concept that periodontal dysbiosis is the result of a process of microbial succession without replacement, more species were detected in disease than in health. However, gingivitis-associated communities were more diverse than those from subjects with periodontitis, suggesting that certain species ultimately become dominant as dysbiosis progresses. We identified the bacterial species associated with each periodontal condition and prevalent species that do not change in abundance from one state to another (core species), and we also outlined species co-occurrence patterns via network analysis. Most periodontitis-associated species were rarely detected in health but were frequently detected, albeit in low abundance, in gingivitis, which suggests that gingivitis and periodontitis are a continuum. Overall, we provide a framework of subgingival microbiome shifts, which can be used to generate hypotheses with respect to community assembly processes and the emergence of periodontal dysbiosis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogen Porphyromonas gingivalis. This bacterial pathogen overcomes the requirement for an endogenous cue by utilizing a cell-density dependent, growth-promoting, soluble molecule provided by the symbiotic early colonizer Veillonella parvula, but not produced by other commensals tested. Our work shows that exchange of cell-density-dependent diffusible cues between specific early and late colonizing species in a polymicrobial community drives microbial successions, pathogen colonization and disease development, representing a target process for manipulation of the microbiome towards the healthy state.

The microbial communities that inhabit the gingival crevice are responsible for the pathological processes that affect the periodontium. The changes in composition and function of subgingival bacteria as disease develops have been extensively studied. Subgingival communities, however, also contain fungi, Archaea, and viruses, which could contribute to the dysbiotic processes associated with periodontal diseases. High-throughput DNA sequencing has facilitated a better understanding of the mycobiome, archaeome, and virome. However, the number of studies available on the nonbacterial components of the subgingival microbiome remains limited in comparison with publications focusing on bacteria. Difficulties in characterizing fungal, archaeal, and viral populations arise from the small portion of the total metagenome mass they occupy and lack of comprehensive reference genome databases. In addition, specialized approaches potentially introducing bias are required to enrich for viral particles, while harsh methods of cell lysis are needed to recover nuclei acids from certain fungi. While the characterization of the subgingival diversity of fungi, Archaea and viruses is incomplete, emerging evidence suggests that they could contribute in different ways to subgingival dysbiosis. Certain fungi, such as Candida albicans are suggested to facilitate colonization of bacterial pathogens. Methanogenic Archaea are associated with periodontitis severity and are thought to partner synergistically with bacterial fermenters, while viruses may affect immune responses or shape microbial communities in ways incompletely understood. This review describes the manner in which omics approaches have improved our understanding of the diversity of fungi, Archaea, and viruses within subgingival communities. Further characterization of these understudied components of the subgingival microbiome is required, together with mechanistic studies to unravel their ecological role and potential contributions to dysbiosis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent efforts to understand the oral microbiome have focused on its fungal component. Since fungi occupy a low proportion of the oral microbiome biomass, mycobiome studies rely on sequencing of internal transcribed spacer (ITS) amplicons. ITS-based studies usually detect hundreds of fungi in oral samples. Here, we review the oral mycobiome, critically appraising the significance of such large fungal diversity. When harsh lysis methods are used to extract DNA, 2 oral mycobiome community types (mycotypes) are evident, each dominated by only 1 genus, either Candida or Malassezia . The rest of the diversity in ITS surveys represents low-abundance fungi possibly acquired from the environment and ingested food. So far, Candida is the only genus demonstrated to reach a significant biomass in the oral cavity and clearly shown to be associated with a distinct oral ecology. Candida thrives in the presence of lower oral pH and is enriched in caries, with mechanistic studies in animal models suggesting it participates in the disease process by synergistically interacting with acidogenic bacteria. Candida serves as the main etiological agent of oral mucosal candidiasis, in which a Candida -bacteriome partnership plays a key role. The function of other potential oral colonizers, such as lipid-dependent Malassezia , is still unclear, with further studies needed to establish whether Malassezia are metabolically active oral commensals. Low-abundance oral mycobiome members acquired from the environment may be viable in the oral cavity, and although they may not play a significant role in microbiome communities, they could serve as opportunistic pathogens in immunocompromised hosts. We suggest that further work is needed to ascertain the significance of oral mycobiome members beyond Candida . ITS-based surveys should be complemented with other methods to determine the in situ biomass and metabolic state of fungi thought to play a role in the oral environment.

Efforts to map gingival tissue proteomes and microbiomes have been hampered by lack of sufficient tissue extraction methods. The pressure cycling technology (PCT) is an emerging platform for reproducible tissue homogenisation and improved sequence retrieval coverage. Therefore, we employed PCT to characterise the proteome and microbiome profiles in healthy and diseased gingival tissue. Healthy and diseased contralateral gingival tissue samples (total n = 10) were collected from five systemically healthy individuals (51.6 ± 4.3 years) with generalised chronic periodontitis. The tissues were then lysed and digested using a Barocycler, proteins were prepared and submitted for mass spectrometric analysis and microbiome DNA for 16S rRNA profiling analysis. Overall, 1,366 human proteins were quantified (false discovery rate 0.22%), of which 69 proteins were differentially expressed (≥2 peptides and p < 0.05, 62 up, 7 down) in periodontally diseased sites, compared to healthy sites. These were primarily extracellular or vesicle-associated proteins, with functions in molecular transport. On the microbiome level, 362 species-level operational taxonomic units were identified. Of those, 14 predominant species accounted for >80% of the total relative abundance, whereas 11 proved to be significantly different between healthy and diseased sites. Among them, Treponema sp. HMT253 and Fusobacterium naviforme and were associated with disease sites and strongly interacted ( r > 0.7) with 30 and 6 up-regulated proteins, respectively. Healthy-site associated strains Streptococcus vestibularis, Veillonella dispar, Selenomonas sp. HMT478 and Leptotrichia sp. HMT417 showed strong negative interactions ( r < -0.7) with 31, 21, 9, and 18 up-regulated proteins, respectively. In contrast the down-regulated proteins did not show strong interactions with the regulated bacteria. The present study identified the proteomic and intra-tissue microbiome profile of human gingiva by employing a PCT-assisted workflow. This is the first report demonstrating the feasibility to analyse full proteome profiles of gingival tissues in both healthy and disease sites, while deciphering the tissue site-specific microbiome signatures., (Copyright © 2020 Bao, Li, Poveda, Qi, Selevsek, Gumus, Emingil, Grossmann, Diaz, Hajishengallis, Bostanci and Belibasakis.)

A broad range of fungi has been detected in molecular surveys of the oral mycobiome. However, knowledge is still lacking on interindividual variability of these communities and the ecologic and clinical significance of oral fungal commensals. In this cross-sectional study, we use internal transcribed spacer 1 amplicon sequencing to evaluate the salivary mycobiome in 59 subjects, 36 of whom were scheduled to receive cancer chemotherapy. Analysis of the broad population structure of fungal communities in the whole cohort identified 2 well-demarcated genus-level community types (mycotypes), with Candida and Malassezia as the main taxa driving cluster partitioning. The Candida mycotype had lower diversity than the Malassezia mycotype and was positively correlated with cancer and steroid use in these subjects, smoking, caries, utilizing a removable prosthesis, and plaque index. Mycotypes were also associated with metabolically distinct bacteria indicative of divergent oral environments, with aciduric species enriched in the Candida mycotype and inflammophilic bacteria increased in the Malassezia mycotype. Similar to their fungal counterparts, coexisting bacterial communities associated with the Candida mycotype showed lower diversity than those associated with the Malassezia mycotype, suggesting that common environmental pressures affected bacteria and fungi. Mycotypes were also seen in an independent cohort of 24 subjects, in which cultivation revealed Malassezia as viable oral mycobiome members, although the low-abundance Malassezia sympodialis was the only Malassezia species recovered. There was a high degree of concordance between the molecular detection and cultivability of Candida , while cultivation showed low sensitivity for detection of the Malassezia mycotype. Overall, our work provides insights into the oral mycobiome landscape, revealing 2 community classes with apparently distinct ecologic constraints and specific associations with coexisting bacteria and clinical parameters. The utility of mycotypes as biomarkers for oral diseases warrants further study.

The last decade has witnessed unparalleled advances in our understanding of the complexity of the oral microbiome and the compositional changes that occur in subgingival biofilms in the transition from health to gingivitis and to destructive periodontal disease. The traditional view, which has held sway for the last 2 decades, that disease is characterized by the outgrowth of a consortium, or consortia, of a limited number of potentially pathogenic organisms, has given way to an alternative paradigm. In this new view, the microbiological changes associated with disease represent whole-scale alterations to the overall microbial population structure and to the functional properties of the entire community. Thus, and in common with other microbially mediated diseases of the gastrointestinal tract, the normally balanced, symbiotic, and generally benign commensal microbiome of the tooth-associated biofilm undergoes dysbiosis to a potentially deleterious microbiota. Coincident with progress in defining the microbiology of these diseases, there have been equally important advances in our understanding of the inflammatory systems of the periodontal tissues, their control, and how inflammation may contribute both to the development of dysbiosis and, in a deregulated state, the destructive disease process. One can therefore speculate that the inflammatory response and the periodontal microbiome are in a bidirectional balance in oral health and a bidirectional imbalance in periodontitis. However, despite these clear insights into both sides of the host/microbe balance in periodontal disease, there remain several unresolved issues concerning the role of the microbiota in disease. These include, but are not limited to, the factors which determine progression from gingivitis to periodontitis in a proportion of the population, whether dysbiosis causes disease or results from disease, and the molecular details of the microbial stimulus responsible for driving the destructive inflammatory response. Further progress in resolving these issues may provide significant benefit to diagnosis, treatment, and prevention., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: This review summarizes mechanisms by which Porphyromonas gingivalis interacts with community members and the host so that it can persist in the periodontium under inflammatory conditions that drive periodontal disease., Recent Findings: Recent advances indicate that, in great part, the pathogenicity of P. gingivalis is dependent upon its ability to establish residence in the subgingival environment and to subvert innate immunity in a manner that uncouples the nutritionally favorable (for the bacteria) inflammatory response from antimicrobial pathways. While the initial establishment of P. gingivalis is dependent upon interactions with early colonizing bacteria, the immune subversion strategies of P. gingivalis in turn benefit co-habiting species., Summary: Specific interspecies interactions and subversion of the host response contribute to the emergence and persistence of dysbiotic communities and are thus targets of therapeutic approaches for the treatment of periodontitis., Competing Interests: Conflict of Interest: George Hajishengallis is an inventor of a patent that describes the use of complement inhibitors for therapeutic purposes in periodontal disease. Patricia I. Diaz declares that she has no conflict of interest.

Oral microbial communities are extraordinarily complex in taxonomic composition and comprise interdependent biological systems. The bacteria, archaea, fungi, and viruses that thrive within these communities engage in extensive cell-cell interactions, which are both beneficial and antagonistic. Direct physical interactions among individual cells mediate large-scale architectural biofilm arrangements and provide spatial proximity for chemical communication and metabolic cooperation. In this review, we summarize recent work in identifying specific molecular components that mediate cell-cell interactions and describe metabolic interactions, such as cross-feeding and exchange of electron acceptors and small molecules, that modify the growth and virulence of individual species. We argue, however, that although pairwise interaction models have provided useful information, complex community-like systems are needed to study the properties of oral communities. The networks of multiple synergistic and antagonistic interactions within oral biofilms give rise to the emergent properties of persistence, stability, and long-range spatial structure, with these properties mediating the dysbiotic transitions from health to oral diseases. A better understanding of the fundamental properties of interspecies networks will lead to the development of effective strategies to manipulate oral communities.

Oral candidiasis is a common side effect of cancer chemotherapy. To better understand predisposing factors, we followed forty-five subjects who received 5-fluorouracil- or doxorubicin-based treatment, during one chemotherapy cycle. Subjects were evaluated at baseline, prior to the first infusion, and at three additional visits within a two-week window. We assessed the demographic, medical and oral health parameters, neutrophil surveillance, and characterized the salivary bacteriome and mycobiome communities through amplicon high throughput sequencing. Twenty percent of all subjects developed oral candidiasis. Using multivariate statistics, we identified smoking, amount of dental plaque, low bacteriome and mycobiome alpha-diversity, and the proportions of specific bacterial and fungal taxa as baseline predictors of oral candidiasis development during the treatment cycle. All subjects who developed oral candidiasis had baseline microbiome communities dominated by Candida and enriched in aciduric bacteria. Longitudinally, oral candidiasis was associated with a decrease in salivary flow prior to lesion development, and occurred simultaneously or before oral mucositis. Candidiasis was also longitudinally associated with a decrease in peripheral neutrophils but increased the neutrophil killing capacity of Candida albicans . Oral candidiasis was not found to be associated with mycobiome structure shifts during the cycle but was the result of an increase in Candida load, with C. albicans and Candida dubliniensis being the most abundant species comprising the salivary mycobiome of the affected subjects. In conclusion, we identified a set of clinical and microbiome baseline factors associated with susceptibility to oral candidiasis, which might be useful tools in identifying at risk individuals, prior to chemotherapy.

Background: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues., Results: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity., Conclusions: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.

Infectious complications are a common cause of morbidity and mortality in cancer patients undergoing chemotherapy due to increased risk of oral and gastrointestinal candidiasis, candidemia and septicemia. Interactions between C. albicans and endogenous mucosal bacteria are important in understanding the mechanisms of invasive infection. We published a mouse intravenous chemotherapy model that recapitulates oral and intestinal mucositis, and myelosuppression in patients receiving 5-fluorouracil. We used this model to study the influence of C. albicans on the mucosal bacterial microbiome and compared global community changes in the oral and intestinal mucosa of the same mice. We validated 16S rRNA gene sequencing data by qPCR, in situ hybridization and culture approaches. Mice receiving both 5Fu and C. albicans had an endogenous bacterial overgrowth on the oral but not the small intestinal mucosa. C. albicans infection was associated with loss of mucosal bacterial diversity in both sites with indigenous Stenotrophomonas, Alphaproteobacteria and Enterococcus species dominating the small intestinal, and Enterococcus species dominating the oral mucosa. Both immunosuppression and Candida infection contributed to changes in the oral microbiota. Enterococci isolated from mice with oropharyngeal candidiasis were implicated in degrading the epithelial junction protein E-cadherin and increasing the permeability of the oral epithelial barrier in vitro. Importantly, depletion of these organisms with antibiotics in vivo attenuated oral mucosal E-cadherin degradation and C. albicans invasion without affecting fungal burdens, indicating that bacterial community changes represent overt dysbiosis. Our studies demonstrate a complex interaction between C. albicans, the resident mucosal bacterial microbiota and the host environment in pathogenesis. We shed significant new light on the role of C. albicans in shaping resident bacterial communities and driving mucosal dysbiosis., Competing Interests: N/A

Introduction: This study aims to obtain data on the prevalence and incidence of structural heart disease in a population setting and, to analyse and present those data on the application of spatial and machine learning methods that, although known to geography and statistics, need to become used for healthcare research and for political commitment to obtain resources and support effective public health programme implementation., Methods and Analysis: We will perform a cross-sectional survey of randomly selected residents of Salamanca (Spain). 2400 individuals stratified by age and sex and by place of residence (rural and urban) will be studied. The variables to analyse will be obtained from the clinical history, different surveys including social status, Mediterranean diet, functional capacity, ECG, echocardiogram, VASERA and biochemical as well as genetic analysis., Ethics and Dissemination: The study has been approved by the ethical committee of the healthcare community. All study participants will sign an informed consent for participation in the study. The results of this study will allow the understanding of the relationship between the different influencing factors and their relative importance weights in the development of structural heart disease. For the first time, a detailed cardiovascular map showing the spatial distribution and a predictive machine learning system of different structural heart diseases and associated risk factors will be created and will be used as a regional policy to establish effective public health programmes to fight heart disease. At least 10 publications in the first-quartile scientific journals are planned., Trial Registration Number: NCT03429452., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Periodontitis is one of the most common human inflammatory diseases, yet the mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion of resident memory T helper 17 (T H 17) cells in human periodontitis. Phenocopying humans, T H 17 cells expanded in murine experimental periodontitis through local proliferation. Unlike homeostatic oral T H 17 cells, which accumulate in a commensal-independent and interleukin-6 (IL-6)-dependent manner, periodontitis-associated expansion of T H 17 cells was dependent on the local dysbiotic microbiome and required both IL-6 and IL-23. T H 17 cells and associated neutrophil accumulation were necessary for inflammatory tissue destruction in experimental periodontitis. Genetic or pharmacological inhibition of T H 17 cell differentiation conferred protection from immunopathology. Studies in a unique patient population with a genetic defect in T H 17 cell differentiation established human relevance for our murine experimental studies. In the oral cavity, human T H 17 cell defects were associated with diminished periodontal inflammation and bone loss, despite increased prevalence of recurrent oral fungal infections. Our study highlights distinct functions of T H 17 cells in oral immunity and inflammation and paves the way to a new targeted therapeutic approach for the treatment of periodontitis., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Studies in patients with genetic defects can provide unique insights regarding the role of specific genes and pathways in humans. Patients with defects in the Th17/IL-17 axis, such as patients harboring loss-of-function STAT3 mutations (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral fungal infections. Our studies aimed to comprehensively evaluate consequences of STAT3 deficiency on the oral commensal microbiome. We characterized fungal and bacterial communities in AD-HIES in the presence and absence of oral fungal infection compared with healthy volunteers. Analyses of oral mucosal fungal communities in AD-HIES revealed severe dysbiosis with dominance of Candida albicans (C. albicans) in actively infected patients and minimal representation of health-associated fungi and/or opportunists. Bacterial communities also displayed dysbiosis in AD-HIES, particularly in the setting of active Candida infection. Active candidiasis was associated with decreased microbial diversity and enrichment of the streptococci Streptococcus oralis (S. oralis) and S. mutans, suggesting an interkingdom interaction of C. albicans with oral streptococci. Increased abundance of S. mutans was consistent with susceptibility to dental caries in AD-HIES. Collectively, our findings illustrate a critical role for STAT3/Th17 in the containment of C. albicans as a commensal organism and an overall contribution in the establishment of fungal and bacterial oral commensal communities.

Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti-neoplastic treatment. There is a lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis because relevant experimental models are non-existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy-induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy-induced mucositis was developed based on a human oral epithelial cell line and a fibroblast-embedded collagen matrix. Treatment of organotypic constructs with 5-fluorouracil (5-FU) reproduced major histopathologic characteristics of oral mucositis, such as DNA synthesis inhibition, apoptosis and cytoplasmic vacuolation, without compromising the three-dimensional structure of the multilayer organotypic mucosa. Although structural integrity of the model was preserved, 5-FU treatment resulted in a widening of epithelial intercellular spaces, characterized by E-cadherin dissolution from adherens junctions. In a neutrophil transmigration assay we discovered that this treatment facilitated transport of neutrophils through epithelial layers. Moreover, 5-FU treatment stimulated key proinflammatory cytokines that are associated with the pathogenesis of oral mucositis. 5-FU treatment of mucosal constructs did not significantly affect fungal or bacterial biofilm growth under the conditions tested in this study; however, it exacerbated the inflammatory response to certain bacterial and fungal commensals. These findings suggest that commensals may play a role in the pathogenesis of oral mucositis by amplifying the proinflammatory signals to mucosa that is injured by cytotoxic chemotherapy., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Knowledge Transfer Statement: This article discusses the proceedings of the conference organized by the Task Force on Design and Analysis in Oral Health Research on the new advances in host-microbiome interactions, analytical methods, and their implication in inflammatory periodontal disease management., Competing Interests: The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

The oral microbiome has been implicated as a trigger for immune responsiveness in the oral cavity, particularly in the setting of the inflammatory disease periodontitis. The protocol presented here is aimed at characterizing the oral microbiome in murine models at steady state and during perturbations of immunity or physiology. Herein, we describe murine oral microbiome sampling procedures, processing of low biomass samples and subsequent microbiome characterization based on 16S rRNA gene sequencing., Competing Interests: The authors do not have any conflict of interest or competing interests to declare.

The three main oral diseases of humans, that is, caries, periodontal diseases, and oral candidiasis, are associated with microbiome shifts initiated by changes in the oral environment and/or decreased effectiveness of mucosal immune surveillance. In this review, we discuss the role that microbial-based therapies may have in the control of these conditions. Most investigations on the use of microorganisms for management of oral disease have been conducted with probiotic strains with some positive but very discrete clinical outcomes. Other strategies such as whole oral microbiome transplantation or modification of community function by enrichment with health-promoting indigenous oral strains may offer more promise, but research in this field is still in its infancy. Any microbial-based therapeutics for oral conditions, however, are likely to be only one component within a holistic preventive strategy that should also aim at modification of the environmental influences responsible for the initiation and perpetuation of microbiome shifts associated with oral dysbiosis.

Research on oral fungi has centered on Candida. However, recent internal transcribed spacer (ITS)-based studies revealed a vast number of fungal taxa as potential oral residents. We review DNA-based studies of the oral mycobiome and contrast them with cultivation-based surveys, showing that most genera encountered by cultivation have also been detected molecularly. Some taxa such as Malassezia, however, appear in high prevalence and abundance in molecular studies but have not been cultivated. Important technical and bioinformatic challenges to ITS-based oral mycobiome studies are discussed. These include optimization of sample lysis, variability in length of ITS amplicons, high intra-species ITS sequence variability, high inter-species variability in ITS copy number and challenges in nomenclature and maintenance of curated reference databases. Molecular surveys are powerful first steps to characterize the oral mycobiome but further research is needed to unravel which fungi detected by DNA are true oral residents and what role they play in oral homeostasis.

Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism. Accumulation of Th17 cells at the gingiva was driven in response to the physiological barrier damage that occurs during mastication. Physiological mechanical damage, via induction of interleukin 6 (IL-6) from epithelial cells, tailored effector T cell function, promoting increases in gingival Th17 cell numbers. These data highlight that diverse tissue-specific mechanisms govern education of Th17 cell responses and demonstrate that mechanical damage helps define the immune tone of this important oral barrier., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Tissues surrounding dental implants and teeth develop clinical inflammation in response to microbial stimuli. However, the literature suggests that differences exist in the microbial insult and inflammatory responses leading to gingivitis and peri-implant mucositis. In this pilot study, the authors use for the first time a systems biology approach to comprehensively evaluate clinical parameters, selected inflammatory markers, and the microbiome of subject-matched tooth and implant sites during native inflammation and in response to experimental plaque accumulation. Fifteen subjects with 2 posterior implants and corresponding contralateral teeth were examined at enrollment; at day 0, after reinstitution of gingival/mucosal health; at days 7, 14, and 21, during stent-mediated oral hygiene (OH) abstention; and at day 42, after resumption of OH. The subgingival microbiome was evaluated via 16S rRNA gene sequencing and 8 selected inflammatory markers measured in crevicular fluid. Comparison of teeth and implants via general linear models based on orthogonal polynomials showed similar responses in clinical parameters, inflammatory mediators, and proportions of individual microbial taxa during OH abstention. Implants, however, accumulated less plaque and underwent more heterogeneous shifts in microbiome structure. A multilevel, within-group, sparse partial least squares analysis of covariation of microbial, inflammatory, and clinical parameters throughout all study visits found inflammation around teeth and implants positively correlated with IL-1 alpha and IL-1 beta and with the proportions of Selenomonas, Prevotella, and 5 species-level phylotypes. Gingivitis, however, showed a stronger positive correlation with lactoferrin and IL-1ra and a stronger negative correlation with Rothia. Peri-implant mucositis, on the contrary, correlated positively with certain microbial taxa not associated with gingivitis by a previous study or the current one. In summary, differences existed between implants and tooth sites in microbiome evolution during OH abstention and in the correlation of specific inflammatory mediators and microbial taxa with clinical inflammation. Common biological features, however, were also identified for gingivitis and mucositis.

Background: Probiotics are living microorganisms that provide beneficial effects for the host when administered in proper quantities. The aim of this double-masked placebo-controlled parallel-arm randomized clinical trial is to evaluate the clinical effects of a Lactobacillus rhamnosus SP1-containing probiotic sachet as an adjunct to non-surgical therapy., Methods: Twenty-eight systemically healthy volunteers with chronic periodontitis were recruited and monitored clinically at baseline and 3, 6, 9, and 12 months after therapy. Clinical parameters measured included plaque accumulation, bleeding on probing, probing depths (PDs), and clinical attachment loss. Patients received non-surgical therapy, including scaling and root planing (SRP), and were assigned randomly to a test (SRP + probiotic, n = 14) or control (SRP + placebo, n = 14) group. The intake, once a day for 3 months, of an L. rhamnosus SP1 probiotic sachet commenced after the last session of SRP., Results: Both test and control groups showed improvements in clinical parameters at all time points evaluated. However, the test group showed greater reductions in PD than the control. Also, at initial visits and after 1-year follow-up, the test group showed a statistically significant reduction in the number of participants with PD ≥6 mm, indicating a reduced need for surgery, in contrast to the placebo group., Conclusion: The results of this trial indicate that oral administration of L. rhamnosus SP1 resulted in similar clinical improvements compared with SRP alone.

High-throughput 16S rRNA gene sequencing has allowed the characterization of subgingival microbiome shifts from health to periodontitis identifying health-associated, periodontitis-associated and core species, which preserve their proportions from health to disease. The development of gingivitis is also characterized by distinct shifts. Microbiome shifts resemble microbial successions and result from interspecies interactions and community adaptation to the changing environment as inflammation ensues. Gingivitis-associated and core species are proposed as likely mediators of microbiome transitions.

Background: Evidence supports high prevalence of periodontitis in patients with chronic kidney disease. Several renal factors have been proposed as possible modifiers of periodontitis pathogenesis in this population. In this cross sectional study, we investigated whether distinct microbial profiles in renal patients could explain high periodontitis prevalence., Methods: We characterized the subgingival microbiome in 14 End Stage Renal Disease (ESRD) and 13 control individuals with chronic periodontitis with similar demographic and clinical parameters. Medical, demographic and periodontal parameters were recorded. Subgingival biofilm samples were collected from the deepest pocket in two different quadrants and characterized via 454-pyrosequencing of the 16S rRNA gene., Results: We found 874 species-level operational taxonomic units (OTU) across samples. Renal and control groups did not differ in the individual proportions of periodontitis-associated taxa. However, in principal coordinate plots of distance among samples based on OTU prevalence, some renal patients clustered apart from controls, with the microbial communities of these outlier subjects showing less diversity. Univariate correlation analysis showed a significant negative correlation between dialysis vintage and community diversity., Conclusions: Within the study limitations, dialysis vintage was associated with a less diverse periodontal microbial community in ESRD suggesting the need for further research.

Periodontitis is an inflammatory condition that affects the supporting tissues surrounding teeth. The occurrence of periodontitis is associated with shifts in the structure of the communities that inhabit the gingival sulcus. Although great inter-subject variability in the subgingival microbiome has been observed in subjects with periodontitis, it is unclear whether distinct community types exist and if differences in microbial signatures correlate with host characteristics or with the variable clinical presentations of periodontitis. Therefore, in this study we explored the existence of different community types in periodontitis and their relationship with host demographic, medical and disease-related clinical characteristics. Clustering analyses of microbial abundance profiles suggested two types of communities (A and B) existed in the 34 subjects with periodontitis evaluated. Type B communities harbored greater proportions of certain periodontitis-associated taxa, including species historically associated with the disease, such as Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola, and taxa recently linked to periodontitis. In contrast, subjects with type A communities had increased proportions of different periodontitis-associated species, and were also enriched for health-associated species and core taxa (those equally prevalent in health and periodontitis). Periodontitis subgingival clusters were not associated with demographic, medical or disease-specific clinical parameters other than periodontitis extent (proportion of sites affected), which positively correlated with the total proportion of cluster B signature taxa. In conclusion, two types of microbial communities were detected in subjects with periodontitis. Host demographics and underlying medical conditions did not correlate with these profiles, which instead appeared to be related to periodontitis extent, with type B communities present in more widespread disease cases. The two identified periodontitis profiles may represent distinct dysbiotic processes potentially requiring community-tailored therapeutic interventions.