Functional study of the periodontal microbiome and host immune response in T2D patients with different levels of glycemic control

不同血糖控制水平的2型糖尿病患者牙周微生物组和宿主免疫反应的功能研究

• 批准号: 10427068
• 负责人: Huiying Li
• 金额: $ 57.08万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-18 至 2023-08-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427068
• 关键词: Address; Adult; Affect; Aftercare; American; Automobile Driving; Behavior; Biological Models; Chronic; Chronic Disease; Clinical; Communities; Development; Diabetes Mellitus; Diagnosis; Disease; Etiology; Future; Gene Expression Profile; Genes; Genetic Transcription; Glycosylated hemoglobin A; Health; Human; Immune response; Individual; Inflammation; Inflammatory; Inflammatory Response; Investigation; Knowledge; Lead; Light; Link; Metabolic; Metagenomics; Microbe; Microbial Biofilms; Mouth Diseases; Nature; Non-Insulin-Dependent Diabetes Mellitus; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Pattern; Periodontal Diseases; Periodontal Pocket; Periodontitis; Play; Population; Prevention; Prevention approach; Production; Public Health; Publishing; Reporting; Research; Ribosomal RNA; Risk; Role; Severities; Shapes; Shotguns; Systemic disease; Taxonomy; Testing; Tissues; Tooth Diseases; Work; base; case control; cytokine; design; diabetes management; glycemic control; high risk; host microbiome; immune function; improved; in vivo; individual patient; innovation; insight; member; microbial; microbiome; microbiome composition; microorganism; neutrophil; non-diabetic; novel strategies; oral microbiome; response; subgingival microbiome; success; systemic inflammatory response; treatment effect; treatment response

PROJECT SUMMARY Type 2 diabetes (T2D) is a significant and increasingly prevalent disease in the US population. It substantially increases the risk for chronic periodontitis (PD), another important public health problem affecting nearly half of the American adults. Conversely, PD adversely affects glycemic control in T2D patients, supporting a bi-directional relationship between these two major chronic diseases. Currently, the mechanisms underlying this two-way relationship are not well understood. PD is an inflammatory disease associated with the alterations of the subgingival microbiome. In T2D, the host immune response is altered, which could affect the host-biofilm interaction of the subgingival microbiome and thus disease etiology. However, comprehensive analysis of the subgingival microbiome and its changes upon treatment, and the associated functions including host responses in T2D with PD is lacking. To address this knowledge gap, we propose to investigate the subgingival microbiome and host responses in T2D patients with different levels of glycemic control and systemically healthy, non-diabetic individuals (ND) with PD. Specifically, we hypothesize that the response of the subgingival microbiome to PD treatment in T2D patients with different levels of glycemic control and ND individuals differ at the levels of transcriptional activities and spatial organization of key community members. We also hypothesize that the host immune responses including neutrophil behavior differ significantly among the groups and play an important role in shaping the microbiome. To reveal whether microbiome composition and activities differ between T2D and ND in response to treatment, in Aim 1, we will characterize the composition and transcriptional activities of the subgingival microbiome in T2D patients with well, moderately, or poorly controlled glycemic level, in comparison to ND subjects, prior to and after periodontal treatment. In Aim 2, we will focus on the spatial organization of key PD-associated taxa to reveal their relationship in vivo in T2D and ND patient groups before and after treatment. In Aim 3, we will investigate host cytokine production and neutrophil responses to microbial challenge with core PD-associated species and compare the differences among the T2D and ND patient groups. This research will address a fundamental gap in our knowledge of the subgingival microbiome in a population at high risk for PD, which may lead to further studies for the development of innovative clinical approaches to PD diagnosis, prevention and management in T2D population. This study can also provide a model system for future investigations of the interplay between a localized microbiome and a systemic disease. The success of this project will not only shed light on the oral microbiome and PD pathogenesis in relation to T2D but also have a significant impact on future investigations of host - microbiome interactions.

项目总结