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

• 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
• 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

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.

项目概要 牙周炎和 II 型糖尿病 (T2D) 是同时发生的疾病，也是最流行的疾病之一 在美国，估计有 46.5% 的成年人患有慢性疾病，9.4% 的成年人患有慢性疾病 患有后者，65岁以上的糖尿病成人中有62.3%同时患有这两种疾病。 T2D，其特点是 慢性全身炎症状态，可通过宿主免疫反应失调和牙周炎导致牙周炎。 全身炎症和口腔生态失调之间的正反馈循环。观察发现牙周炎 对血糖控制、胰岛素抵抗和糖尿病并发症（如神经病变、心血管疾病）产生不利影响 疾病，甚至死亡已被广泛接受，但其潜在机制尚不清楚。牙周炎已经出现 作为肠道微生物组的潜在调节剂，其在调节系统和代谢健康方面的作用是 越来越被认可。多项研究指出肠道微生物群失调是代谢的一个促成因素 疾病、炎症性肠病（IBD）、结直肠癌和类风湿性关节炎。结合 有证据表明口腔菌群失调与肠道微生物组组成的变化有关，并且口腔微生物使 T2D 中肠道微生物组特征的上升，口腔-肠道微生物组轴作为两者之间的联系的基本原理是存在的 牙周炎和糖尿病。 NRSA F30 提案的目标是评估牙周炎及其影响 相关的口腔微生物群失调，对代谢重要的肠道微生物群的代谢途径 疾病和 T2D。该提案的总体假设是牙周炎改变肠道微生物组 口腔至肠道的菌株传播会导致 T2D 的代谢功能障碍和炎症。目的 目标 1 是确定微生物特定菌株水平的遗传变异和口腔菌群失调是否与 肠道微生物组的功能变化。目标 2 的目的是测试口腔至肠道的菌株传播 牙周炎改变肠道微生物组并导致与 T2D 相关的不良结果的机制。 使用与受试者匹配的菌斑和粪便样本，口腔和肠道微生物组将在菌株特征 将为每个微生物组重建水平分辨率和代谢谱。中概述的实验 该提案将确定特定口腔菌株和口腔至肠道菌株传播在促进 T2D 中牙周炎的病理系统影响。这项工作将在布法罗大学进行 牙科医学院，微生物组研究专家 Patricia Diaz 博士的实验室。这 培训计划是为传染病领域的医师科学家的发展而量身定制的，其中包括 传染病和内分泌学的临床指导以获得跨学科经验， 反映本提案的研究目标。这些纵向临床指导将取得成功 医生科学家，他们也将直接参与拟议的研究，从而提供综合的 奖学金期间的指导。