Oral to Gut Microbiome Transmission in Periodontitis and Type 2 Diabetes

牙周炎和 2 型糖尿病中口腔至肠道微生物群的传播

基本信息

批准号：
10619449
负责人：
Armond June
金额：
$ 3.34万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
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：
2022-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10619449
关键词：
16S ribosomal RNA sequencing Activities of Daily Living Adult Affect Aftercare Animals Bacteroides Branched-Chain Amino Acids Cardiovascular Diseases Cessation of life Chronic Chronic Disease Clinical Cohort Analysis Colorectal Cancer Communicable Diseases Complications of Diabetes Mellitus Dental Schools Development Diabetes Mellitus Disease Elderly Endocrinology Endotoxemia Feces Feedback Fellowship Firmicutes Functional disorder Genes Genetic Variation Glycosylated Hemoglobin Glycosylated hemoglobin A Goals Health Hemoglobin concentration result Human Immune response Individual Inflammation Inflammatory Inflammatory Bowel Diseases Insulin Resistance Knowledge Laboratories Link Longitudinal cohort Mediating Medicine Mentorship Metabolic Metabolic Diseases Metabolic Pathway Metabolic dysfunction Methodology Microbe Molecular Mouth Diseases National Research Service Awards Neuropathy Non-Insulin-Dependent Diabetes Mellitus Oral Oral Characters Outcome Oxidative Stress Pathogenicity Pathologic Pathway interactions Patients Pattern Periodontitis Permeability Physicians Population Preceptorship Research Resolution Rheumatoid Arthritis Risk Risk Factors Role Sampling Scientist Severities Shotguns Signal Transduction Testing Training United States Universities Volatile Fatty Acids Work diabetes control diabetes pathogenesis diabetic dysbiosis experience experimental study glycemic control gut inflammation gut microbiome high risk immunogenicity improved insight intestinal barrier metabolic phenotype metabolic profile metagenomic sequencing microbial microbiome microbiome composition microbiome research microbiome sequencing microbiome signature modifiable risk negative affect novel oral microbiome pathobiont pathogen sugar systemic inflammatory response transmission process

16S ribosomal RNA sequencing Activities of Daily Living Adult Affect Aftercare Animals Bacteroides Branched-Chain Amino Acids Cardiovascular Diseases Cessation of life Chronic Chronic Disease Clinical Cohort Analysis Colorectal Cancer Communicable Diseases Complications of Diabetes Mellitus Dental Schools Development Diabetes Mellitus Disease Elderly Endocrinology Endotoxemia Feces Feedback Fellowship Firmicutes Functional disorder Genes Genetic Variation Glycosylated Hemoglobin Glycosylated hemoglobin A Goals Health Hemoglobin concentration result Human Immune response Individual Inflammation Inflammatory Inflammatory Bowel Diseases Insulin Resistance Knowledge Laboratories Link Longitudinal cohort Mediating Medicine Mentorship Metabolic Metabolic Diseases Metabolic Pathway Metabolic dysfunction Methodology Microbe Molecular Mouth Diseases National Research Service Awards Neuropathy Non-Insulin-Dependent Diabetes Mellitus Oral Oral Characters Outcome Oxidative Stress Pathogenicity Pathologic Pathway interactions Patients Pattern Periodontitis Permeability Physicians Population Preceptorship Research Resolution Rheumatoid Arthritis Risk Risk Factors Role Sampling Scientist Severities Shotguns Signal Transduction Testing Training United States Universities Volatile Fatty Acids Work diabetes control diabetes pathogenesis diabetic dysbiosis experience experimental study glycemic control gut inflammation gut microbiome high risk immunogenicity improved insight intestinal barrier metabolic phenotype metabolic profile metagenomic sequencing microbial microbiome microbiome composition microbiome research microbiome sequencing microbiome signature modifiable risk negative affect novel oral microbiome pathobiont pathogen sugar systemic inflammatory response transmission process

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项目摘要

Project Summary Periodontitis and Type II Diabetes (T2D) are co-occurring diseases and among the most prevalent chronic illnesses in the United States with an estimated 46.5% of adults suffering from the former, 9.4% adults suffering from the latter, and 62.3% of diabetic adults older than 65 burdened by both. T2D, characterized by a state of chronic systemic inflammation, can lead to periodontitis via dysregulated host immune responses and a positive feedback loop between systemic inflammation and oral dysbiosis. The observation that periodontitis adversely affects glycemic control, insulin resistance, and diabetic complications like neuropathy, cardiovascular disease, and even death is well accepted, but the underlying mechanism is unknown. Periodontitis has emerged as a potential modifier of the gut microbiome, whose role in regulating systemic and metabolic health is increasingly being recognized. Multiple studies point to gut microbiome dysbiosis as a contributor to metabolic disorders, inflammatory bowel disease (IBD), colorectal cancer and rheumatoid arthritis. Combined with evidence oral dysbiosis is associated with gut microbiome compositional changes, and, that oral microbes make up gut microbiome signatures in T2D, rationale exists for the oral-gut microbiome axis as a link between periodontitis and diabetes. The goal of this NRSA F30 proposal is to evaluate the effect of periodontitis, and its associated mouth microbiome dysbiosis, on metabolic pathways of the gut microbiome important to metabolic disorders and T2D. The overarching hypothesis of this proposal is that periodontitis alters the gut microbiome vis oral-to-gut strain transmission to contribute to metabolic dysfunction and inflammation in T2D. The purpose of Aim 1 is to determine if microbial specific strain-level genetic variation and oral dysbiosis are associated with functional changes in the gut microbiome. The purpose of Aim 2 is to test oral-to-gut strain transmission as a mechanism by which periodontitis alters the gut microbiome, and contributes to poor outcomes related to T2D. Using subject-matched plaque and feces samples, the oral and gut microbiomes will be characterized at strain- level resolution, and metabolic profiles will be reconstructed for each microbiome. The experiments outlined in this proposal will determine the role of specific oral strains and oral-to-gut strain transmission in contributing to the pathologic systemic effects of periodontitis seen in T2D. This work will take place at the University at Buffalo, School of Dental Medicine, in the laboratory of Dr. Patricia Diaz, who is an expert in microbiome research. The training plan is tailored for development as a physician-scientist in the field of infectious disease, and will include clinical preceptorships in infectious disease and endocrinology in order to gain cross-disciplinary experience, reflecting the research goals of this proposal. These longitudinal clinical preceptorships will be with successful physician-scientists, who also will be directly involved in the proposed research, thereby providing integrated mentorship over the course of the fellowship.

项目摘要牙周炎和II型糖尿病（T2D）是同时发生的疾病，最普遍美国的慢性疾病估计有46.5％的成年人，9.4％的成年人患有后者的患者和62.3％的糖尿病成年人都受到了65岁的负担。 T2D，以一个为特征慢性全身炎症状态，可以通过失调的宿主免疫反应和A导致牙周炎全身炎症和口腔失调之间的正反馈回路。牙周炎的观察不利影响血糖控制，胰岛素抵抗和糖尿病并发症，例如神经病，心血管疾病，甚至死亡都被广泛接受，但潜在的机制尚不清楚。牙周炎已经出现作为肠道微生物组的潜在修饰符，其在调节系统性和代谢健康中的作用是越来越多地被认可。多个研究指出肠道微生物组营养不良是代谢的原因疾病，炎症性肠病（IBD），结直肠癌和类风湿关节炎。与证据口腔失调与肠道微生物组组成变化有关，并且口服微生物使在T2D中，肠道微生物组的特征是口服微生物组轴的基本原理作为链接牙周炎和糖尿病。该NRSA F30提案的目的是评估牙周炎的作用及其相关的口腔微生物组营养不良，在肠道微生物组的代谢途径上对代谢很重要疾病和T2D。该提议的总体假设是牙周炎改变了肠道微生物组口腔到肠道应变的传播有助于T2D中的代谢功能障碍和炎症。目的 AIM 1的是确定微生物特异性应变水平的遗传变异和口服失调与肠道微生物组的功能变化。 AIM 2的目的是测试口服到肠道应变的传播牙周炎改变肠道微生物组的机制，并导致与T2D相关的不良结果。使用受试者匹配的斑块和粪便样品，口服和肠道微生物组将在应变时进行表征水平分辨率和代谢谱将针对每个微生物组重建。概述的实验该提案将确定特定的口服菌株和口服应变的作用在有助于 T2D中看到的牙周炎的病理系统作用。这项工作将在布法罗大学举行牙科医学学院，在微生物组研究专家Patricia Diaz博士的实验室中。这培训计划是针对传染病领域的医师科学家的发展而量身定制的，将包括为了获得跨学科的经验，传染病和内分泌学的临床主持反映该提案的研究目标。这些纵向的临床教育将成功医师科学家也将直接参与拟议的研究，从而提供综合的研究在团契过程中指导。