Biofilm Spatial Structure in the Transition from Health to Periodontal Disease

从健康向牙周病转变的生物膜空间结构

基本信息

批准号：
10674685
负责人：
Alex M Valm
金额：
$ 46.16万
依托单位：
STATE UNIVERSITY OF NEW YORK AT ALBANY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10674685
关键词：
Address Adult Affect Architecture Bacteria Biochemical Canis familiaris Cells Chronic Clinical Markers Coculture Techniques Communities Data Dental Plaque Development Diagnosis Disease Disease Progression Epithelium Fostering Gene Expression Genes Gingiva Gingivitis Health Health Transition Human Image Image Analysis Immune Immune response Immune system Inflammation Inflammatory Inflammatory Response Knowledge Linear Regressions Location Machine Learning Maps Mediating Messenger RNA Metagenomics Microbe Microbial Biofilms Monitor Organism Pathogenicity Patients Periodontal Diseases Periodontitis Play Porphyromonas gingivalis Process Research Role Spatial Distribution Structure Structure-Activity Relationship Sum Surveys Taxon Taxonomy Testing Time Tissue-Specific Gene Expression Tooth structure Work canine model comparative dental biofilm design differential expression dysbiosis healthy volunteer holistic approach human model metagenomic sequencing metatranscriptomics microbial microbial community novel pathobiont pathogen prevent quantitative imaging scaffold subgingival biofilm subgingival microbiome success tooth surface transcriptome sequencing whole genome wisdom tooth

项目摘要

ABSTRACT Periodontal disease is mediated by the dynamic interplay between host inflammation and changes in subgingival biofilm community composition. The keystone pathogen, Porphyromonas gingivalis is known to subvert the immune response to promote inflammation and favorable conditions for pathobiont organisms, while inhibiting immune system clearance of bacteria. Because of this, P. gingivalis has been proposed to initiate periodontal disease. Here we propose a new paradigm for the initiation of periodontal disease, mediated at the gingival margin by long filamentous cells that bring plaque organisms into close or direct contact with the epithelium to initiate inflammation in the form of gingivitis. This reversible inflammatory state then induces dysbiosis in the subgingival community. We will test our hypothesis by imaging intact biofilms on extracted teeth involved in gingivitis and periodontitis, including the biofilm at the gingival margin with FISH probes for up to 18 different taxa. We will further perform quantitative comparative structural analyses of periodontitis associated human biofilms and canine models to specifically identify conserved structural features of pathogenic subgingival biofilms. Lastly, we will map the spatial location of differentially expressed genes within filamentous cells in plaque biofilms when these cells are in direct or close contact with specific partner species. This work will comprise a holistic approach to identify structure-function relationships in healthy and periodontal disease-associated biofilms that underly periodontal disease initiation and progression.

抽象的牙周病是由宿主炎症和牙周组织变化之间的动态相互作用介导的龈下生物膜群落组成。已知主要病原体牙龈卟啉单胞菌破坏免疫反应，促进炎症和致病生物体的有利条件，同时抑制免疫系统清除细菌。因此，牙龈卟啉单胞菌被提议引发牙周病。在这里，我们提出了牙周病发生的新范例，由长丝状细胞在牙龈边缘介导，使牙菌斑生物靠近或直接与上皮接触引发牙龈炎形式的炎症。这种可逆的炎症状态然后引起龈下群落生态失调。我们将通过对完整生物膜进行成像来检验我们的假设拔除牙龈炎和牙周炎的牙齿，包括 FISH 牙龈边缘的生物膜探针多达 18 个不同的分类群。我们将进一步进行定量比较结构分析牙周炎相关的人类生物膜和犬模型，以特异性识别保守的结构特征致病性龈下生物膜。最后，我们将绘制差异表达基因的空间位置图当这些细胞与特定伙伴直接或密切接触时，在斑块生物膜的丝状细胞内物种。这项工作将包括一种整体方法，以确定健康和健康中的结构与功能关系。牙周病相关生物膜是牙周病发生和进展的基础。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Epithelial-derived interleukin-23 promotes oral mucosal immunopathology.

上皮源性白细胞介素 23 促进口腔粘膜免疫病理学。

DOI：
10.1016/j.immuni.2024.02.020
发表时间：
2024-03-01
期刊：
Immunity
影响因子：
32.4
作者：
Tae Sung Kim;Tomoko Ikeuchi;V. Theofilou;D. Williams;T. Greenwell;Armond June;Emmanuel E. Adade;Lu Li;L. Abusleme;N. Dutzan;Yao Yuan;L. Brenchley;N. Bouladoux;Y. Sakamachi;Robert J. Palmer;Ramiro Iglesias;Giorgio Trinchieri;Stavros Garantziotis;Y. Belkaid;A. Valm;Patricia I. Diaz;Steven M. Holl;Niki M Moutsopoulos
通讯作者：
Niki M Moutsopoulos