Periodontitis and cardiometabolic disorders : The role of lipopolysaccharide and endotoxemia

Lipopolysaccharide is a virulence factor of gram-negative bacteria with a crucial importance to the bacterial surface integrity. From the host's perspective, lipopolysaccharide plays a role in both local and systemic inflammation, activates both innate and adaptive immunity, and can trigger inflammation either directly (as a microbe-associated molecular pattern) or indirectly (by inducing the generation of nonmicrobial, danger-associated molecular patterns). Translocation of lipopolysaccharide into the circulation causes endotoxemia, which is typically measured as the biological activity of lipopolysaccharide to induce coagulation of an aqueous extract of blood cells of the assay. Apparently healthy subjects have a low circulating lipopolysaccharide activity, since it is neutralized and cleared rapidly. However, chronic endotoxemia is involved in the pathogenesis of many inflammation-driven conditions, especially cardiometabolic disorders. These include atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome, where endotoxemia has been recognized as a risk factor. The main source of endotoxemia is thought to be the gut microbiota. However, the oral dysbiosis in periodontitis, which is typically enriched with gram-negative bacterial species, may also contribute to endotoxemia. As endotoxemia is associated with an increased risk of cardiometabolic disorders, lipopolysaccharide could be considered as a molecular link between periodontal microbiota and cardiometabolic diseases.Peer reviewe

Subgingival lipid A profile and endotoxin activity in periodontal health and disease.

OBJECTIVES: Regulation of lipopolysaccharide (LPS) chemical composition, particularly its lipid A domain, is an important, naturally occurring mechanism that drives bacteria-host immune system interactions into either a symbiotic or pathogenic relationship. Members of the subgingival oral microbiota can critically modulate host immuno-inflammatory responses by synthesizing different LPS isoforms. The objectives of this study were to analyze subgingival lipid A profiles and endotoxin activities in periodontal health and disease and to evaluate the use of the recombinant factor C assay as a new, lipid A-based biosensor for personalized, point-of-care periodontal therapy. MATERIALS AND METHODS: Subgingival plaque samples were collected from healthy individuals and chronic periodontitis patients before and after periodontal therapy. Chemical composition of subgingival lipid A moieties was determined by ESI-Mass Spectrometry. Endotoxin activity of subgingival LPS extracts was assessed using the recombinant factor C assay, and their inflammatory potential was examined in THP-1-derived macrophages by measuring TNF-α and IL-8 production. RESULTS: Characteristic lipid A molecular signatures, corresponding to over-acylated, bi-phosphorylated lipid A isoforms, were observed in diseased samples. Healthy and post-treatment samples were characterized by lower m/z peaks, related to under-acylated, hypo-phosphorylated lipid A structures. Endotoxin activity levels and inflammatory potentials of subgingival LPS extracts from periodontitis patients were significantly higher compared to healthy and post-treatment samples. CONCLUSIONS: This is the first study to consider structure-function-clinical implications of different lipid A isoforms present in the subgingival niche and sheds new light on molecular pathogenic mechanisms of subgingival biofilm communities. CLINICAL RELEVANCE: Subgingival endotoxin activity (determined by lipid A chemical composition) could be a reliable, bacterially derived biomarker and a risk assessment tool for personalized periodontal care

La arquitectura de los despoblados moriscos en los valles de la Marina Alta.

La tesis realiza el estudio arquitectónico de los núcleos de población de origen islámico y mudéjar, que quedaron abandonados tras la expulsión de los moriscos, en el ámbito geográfico de los Valles de la Marina Alta (Alicante). El método desarrollado se inscribe en la línea de los estudios e investigaciones relacionadas con el conocimiento para la conservación del patrimonio arquitectónico. A partir de una lectura arquitectónica basada en la observación directa de las edificaciones se realiza una planimetría completa del estado actual y un análisis arquitectónico-constructivo. El conjunto de la documentación elaborada para los distintos despoblados constituye un catálogo. Se ha estructurado mediante una ficha, que recoge la información organizada por campos y sirve de guía para el estudio normalizado. La lectura de los datos recogidos ha permitido analizar y conocer los sistemas y procesos constructivos empleados, en concreto la técnica del tapial, pudiendo definirse el sistema empleado: dimensiones, forma de colocación de los componentes principales, materiales, etc. También se ha dado importancia a la definición de los sistemas constructivos: muros, vanos, forjados, etc. El estudio minucioso permite interpretar las superposiciones de fases en el estado actual. Por otra parte se ha definido el espacio arquitectónico generado y la tipología resultante a varios niveles, desde el doméstico hasta el paisajístico en una gradación de escalas en función del menor o mayor nivel de agrupación existente considerando la casa, la aldea (garya), y el territorio. Se ha detectado la presencia de una serie de invariantes en el empleo de diversos tipos y tecnologías constructivas dentro de una tradición cultural musulmana-andalusí prolongada en época mudéjar y morisca.Soler Estrela, A. (2009). La arquitectura de los despoblados moriscos en los valles de la Marina Alta [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/602

Evaluating Clinical Utility of Subgingival and Salivary Endotoxin Activity Levels as Periodontal Biomarkers

OBJECTIVES: The use of periodontal biomarkers for identification and monitoring of unique patient populations could foster better stratification of at-risk groups, increase access to treatment for those most in need, facilitate preventive measures and improve personalised care plans. The aim of this study was to examine the diagnostic and prognostic utility of oral lipopolysaccharides as bacterially-derived periodontal biomarkers. METHODS: Periodontal parameters were recorded, and saliva and subgingival plaque samples were collected at the beginning of the study from periodontally healthy volunteers and periodontitis patients, and three months after completion of conventional periodontal treatment in the periodontitis group. Endotoxin activity in the samples was measured using the recombinant factor C assay. Associations between clinical periodontal parameters and subgingival and salivary endotoxin activities were analysed using a multivariate regression model, while the ROC curve was applied to estimate the sensitivity, specificity and c-statistics for salivary and subgingival endotoxin activities as diagnostic biomarkers for periodontitis. RESULTS: Significant correlations were found between subgingival endotoxin activities, probing pocket depth and periodontal diagnosis, which were independent from patients' age, gender and smoking status. In addition, subgingival endotoxin levels had high specificity and sensitivity in detecting periodontal health and disease (0.91 and 0.85 respectively). Salivary endotoxin activity was positively associated with periodontal diagnosis, mean probing pocket depth, percentages of sites over 4 mm and full mouth bleeding score. However, it was inferior in discriminating patients with stable periodontium from those with periodontitis (sensitivity = 0.69, specificity = 0.61) compared to subgingival endotoxin activity. CONCLUSIONS: Subgingival endotoxin activity has good diagnostic and prognostic values as a site-specific periodontal biomarker and is not influenced by the patient's age, gender or smoking status. In contrast, salivary endotoxin activity, as a patient-level biomarker, is dependent on patient's age, has poorer diagnostic and prognostic capability, but shows good correlations with disease susceptibility and both its extent and severity