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.

项目摘要 牙周炎和II型糖尿病（T2 D）是共同发生的疾病，并且是最普遍的疾病之一。 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。 65岁以上的糖尿病患者中，62.3%的人同时患有糖尿病和糖尿病。T2 D，其特征在于 慢性全身性炎症状态，可通过宿主免疫应答失调和 系统性炎症和口腔生态失调之间的正反馈回路。牙周炎的观察 不利地影响血糖控制、胰岛素抵抗和糖尿病并发症，如神经病变、心血管 疾病，甚至死亡是公认的，但其潜在的机制是未知的。牙周炎已经出现 作为肠道微生物组的潜在修饰剂，其在调节全身和代谢健康方面的作用是 越来越被认可。多项研究指出，肠道微生物组生态失调是代谢的贡献者。 疾病、炎性肠病（IBD）、结肠直肠癌和类风湿性关节炎。结合 证据表明，口腔生态失调与肠道微生物组组成的变化有关， T2 D中的上肠道微生物组特征，存在口腔-肠道微生物组轴作为T2 D中 牙周炎和糖尿病。这个NRSA F30提案的目标是评估牙周炎的影响， 相关的口腔微生物组生态失调，对代谢重要的肠道微生物组的代谢途径 疾病和T2 D。这项提议的首要假设是牙周炎改变了肠道微生物组 vis维斯到肠道的应变传递，以促进T2 D中的代谢功能障碍和炎症。目的 目的1是确定微生物特异性菌株水平的遗传变异和口腔生态失调是否与 肠道微生物组的功能变化。目标2的目的是测试口腔到肠道的菌株传播 牙周炎改变肠道微生物组的机制，并导致与T2 D相关的不良结果。 使用受试者匹配的菌斑和粪便样本，将在菌株- 水平分辨率和代谢谱将为每个微生物组重建。中概述的实验 这项建议将确定特定的口腔菌株和口腔到肠道菌株传播在促进 T2 D中牙周炎的病理性全身效应。这项工作将在布法罗大学进行， 牙科医学院，在帕特里夏迪亚兹博士的实验室，谁是微生物组研究的专家。的 培训计划是专门为发展作为一个医生，科学家在传染病领域，并将包括 传染病和内分泌学的临床导师，以获得跨学科的经验， 反映了本研究的目标。这些纵向临床指导将与成功的 医生科学家，谁也将直接参与拟议的研究，从而提供综合 在奖学金期间提供指导。