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

现在公认的是，组织中细菌的水平和多样性会影响疾病 进展，许多研究已经表征了各种不同的微生物群 患者和患者之间的神经疾病和状况以及已识别的差异 健康对照；产生影响疾病的代谢物的特定物种；以及 研究表明，修改微生物群可以改变疾病的进程。大多数人 这些研究，包括多发性硬化症患者，使用粪便样本检查肠道微生物群 作为肠道菌群的替代品。然而，口腔中的微生物群具有类似的 高度的细菌多样性，并开始更经常地作为一种更容易的 样本来源。在初步研究中，我们分析了一对 同卵双胞胎不符合多发性硬化症(RRMS和CIS)，并发现完全不同 分类学水平，物种差异超过30倍。在新的研究中， 在法国，我们比较了12名多发性硬化症患者和24名健康人的口腔生物群 对照，并发现在门和属水平上的差异。我们现在建议 使用从以下来源获得的样本在更大规模的MS患者队列中重复这些研究 非裔美国人和白人退伍军人患有多发性硬化症；并将他们的口腔生物群与多发性硬化症患者的口腔生物群进行比较 种族、性别和年龄与对照组匹配。生物群将由标准的16S确定 RRNA扩增子测序，并使用现有软件进行比较。我们将测试 如果相对丰度的差异可以区分多发性硬化症和对照，以及如果 AA和白色多发性硬化症患者存在差异。我们将对数据进行分层，以 确定相对丰度是否与年龄、性别或种族有关。我们会 还要测量产生丁酸盐的细菌水平，丁酸盐是一种强大的抗炎药物 分子，这已被证明在MS肠道研究中被减少。总体而言，这是一门知识 口腔微生物组的研究将有助于指导旨在提高水平的治疗方法 有益物种的数量，同时减少潜在有害细菌的水平； 可能被用于监测疾病进展和治疗效果；并可以 提供造成原因的线索