Characterization of the oral microbiome of patients with Multiple Sclerosis

多发性硬化症患者口腔微生物组的特征

• 批准号: 10484039
• 负责人: Douglas L. Feinstein
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484039
• 关键词: 16S ribosomal RNA sequencing; Address; African American; Age; Anti-Inflammatory Agents; Bacteria; Butyrates; Butyrivibrio; Clinical; Computer software; DNA; Data; Diagnosis; Disease; Disease Progression; Disease remission; Ethnic Origin; Etiology; Fatty Acids; France; Gender; Genetic; Home; Human Genetics; Knowledge; Measures; Methods; Monitor; Monozygotic twins; Neurodegenerative Disorders; Oral; Oral Characters; Oral cavity; Patients; Population; Prognosis; Race; Relapse; Reporting; Risk Reduction; Saliva; Salivary; Sampling; Severity of illness; Source; Specificity; Stress; Syndrome; Taxonomy; Testing; Therapeutic; Tissues; Treatment Efficacy; Twin Multiple Birth; Veterans; caucasian American; cohort; comparison control; design; genetic variant; gut microbiome; gut microbiota; infection risk; metabolomics; microbial; microbiome; microbiome analysis; microbiome composition; microbiota; military veteran; multiple sclerosis patient; multiple sclerosis treatment; nervous system disorder; oral microbiome; racial diversity; rapid technique; saliva sample; species difference

It is now accepted that levels and diversity of bacteria present in tissues influence disease progression, and numerous studies have characterized the microbiome in a variety of neurological diseases and conditions and identified differences between patients and healthy controls; specific species that produce metabolites that influence disease; and shown that modifying the microbiome can alter the course of disease. The majority of these studies, including in MS patients, examined the gut microbiome using fecal samples as a surrogate for intestinal flora. However, the microbiome of the oral cavity has a similar high degree of bacterial diversity, and is beginning to be used more often as an easier source of samples. In preliminary studies we analyzed saliva DNA from a pair of monozygotic twins discordant for MS (RRMS versus CIS), and found differences at all taxonomic levels, with species differences greater than 30-fold. In new studies with collaborators in France, we compared the oral biome of 12 MS patients to 24 healthy controls, and found differences at the phylum and genus levels. We now propose to replicate those studies in larger cohorts of MS patients using samples obtained from African American and White Veterans with MS; and compare their oral biome to that of race, gender and age matched controls. The biome will be determined by standard 16S rRNA amplicon sequencing, and comparisons made using available software. We will test if differences in relative abundance can distinguish between MS and controls, and if differences are present in both AA and White MS patients. We will stratify the data to determine if relative abundances are associated with age, gender, or ethnicity. We will also measure levels of bacteria that produce butyrate, a powerful anti-inflammatory molecule, which has been shown to be reduced in MS gut studies. Overall, a knowledge of the oral microbiome will help guide therapeutic approaches designed to increase levels of beneficial species, while reducing levels of potentially detrimental bacteria; and can potentially be used to monitor disease progression and treatment efficacy; and could provide clues as to the contributing causes

现在可以接受的是，组织中存在的细菌的水平和多样性会影响疾病 进展，许多研究表征了各种微生物组 神经系统疾病和条件，并确定了患者之间的差异 健康对照；产生影响疾病的代谢产物的特定物种；和 表明修改微生物组可以改变疾病的进程。大多数 这些研究，包括MS患者，使用粪便样品检查了肠道微生物组 作为肠道菌群的代孕。但是，口腔的微生物组具有相似的 高度的细菌多样性，并开始更频繁地使用更容易 样品的来源。在初步研究中，我们分析了一对 单卵双胞胎与MS（RRMS与顺式）不一致，并且发现差异 分类水平，物种差异大于30倍。在新研究中 法国的合作者，我们将12 ms患者的口服生物群体与24名健康 对照，并在门水平和属水平上发现差异。我们现在建议 使用从 MS的非裔美国人和白人退伍军人；并将他们的口头生物群落与 种族，性别和年龄匹配的控件。生物群组将由标准16S确定 rRNA扩增子测序以及使用可用软件进行的比较。我们将测试 如果相对丰度的差异可以区分MS和对照，以及 AA和白色MS患者均存在差异。我们将将数据分类为 确定相对丰度是否与年龄，性别或种族有关。我们将 还测量产生丁酸酯的细菌水平，这是一种强大的抗炎 在MS肠道研究中已显示出降低的分子。总体而言，一种知识 口服微生物组的中心将有助于指导旨在提高水平的治疗方法 有益的物种，同时降低了潜在有害细菌的水平；可以 有可能用于监测疾病进展和治疗效果；可以 提供有关贡献原因的线索