The oral microbiome as a window into the pathobiology of multiple sclerosis, leading to new ideas for personalized microbial therapies

口腔微生物组作为了解多发性硬化症病理学的窗口，为个性化微生物疗法带来新思路

• 批准号: 10819820
• 负责人: Rachel Lynn Fitzjerrells
• 金额: $ 4.36万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10819820
• 关键词: Affect; Age; Alzheimer' s Disease; Atherosclerosis; Autoimmune Diseases; Bacteria; Biochemical Pathway; Bioinformatics; Biological Markers; Data; Diagnostic; Disease; Environmental Risk Factor; Future; Genes; Genetic; Goals; Health; Heart Diseases; Individual; Inflammatory; Investigation; Iowa; Knowledge; Link; Machine Learning; Maps; Metabolic; Metabolic Pathway; Metagenomics; Microbe; Multiple Sclerosis; Nerve Degeneration; Neurodegenerative Disorders; Oral; Oral Characters; Oral cavity; Oral health; Parkinson Disease; Pathway interactions; Patient Agents; Patients; Persons; Play; Pneumonia; Publishing; Qualifying; Relapsing-Remitting Multiple Sclerosis; Research; Rheumatoid Arthritis; Role; Salivary; Sample Size; Sampling; Shotguns; Taxonomy; Techniques; Testing; Therapeutic; Therapeutic Agents; Training; Universities; Variant; acute stroke; bacterial community; biomarker discovery; classification algorithm; cohort; computer cluster; diagnostic biomarker; dysbiosis; fecal microbiome; gut microbiota; high end computer; insight; machine learning classification; metabolome; metabolomics; metagenome; microbial; microbial based therapy; microbial composition; microbial products; microbiome; microbiome research; multiple sclerosis patient; oral microbial community; oral microbiome; pathobiont; potential biomarker; power analysis; random forest; sex; statistics

Abstract Multiple Sclerosis (MS) affects roughly 2.3 million people worldwide, with Relapsing-Remitting Multiple Sclerosis (RRMS) making up 85% of all MS cases. Although the precise pathobiology of RRMS is not well understood, it is linked to both genetic and environmental factors with an emerging important environmental factor being the microbiome. Recent evidence has shown that the gut microbiota of MS patients differs from that of healthy individuals, suggesting it likely plays a role in pathobiology. However, the importance of the oral microbiome, which is the second most diverse microbiome (first being the gut), as a potential environmental factor is poorly understood. Prior research on the oral microbiome has shown that it can affect not only our oral health, but our systemic health. In fact, other neurodegenerative and autoimmune diseases have been linked with the oral microbiome dysbiosis including Alzheimer’s, Atherosclerosis, and rheumatoid arthritis. Thus, the investigation of the oral microbiome as an environmental factor in the pathobiology of MS is warranted and this proposal will address this gap in knowledge. To test this hypothesis, we will analyze oral biospecimens from 50 patients with RRMS and 50 healthy controls (HC). This cross-sectional comparison will look at the differences and similarities in microbial composition and its associated function between the two groups. Additionally, as the metabolome impacts host health and the microbiome can influence the host metabolome, we will utilize an untargeted metabolomics approach to determine whether MS and HC oral metabolites differ. Lastly, we will correlate the microbes and metabolites to identify the relationships between the oral microbiome and the host metabolites as well as utilize machine learning to identify the most significant features associated with the pathobiology of MS. Overall, this study will help in identifying specific oral microbes, microbial functional pathways, and host metabolite pathways that may be used as potential diagnostic biomarkers as well as therapeutic agents for patients with RRMS.

摘要 多发性硬化（MS）影响全球约230万人，复发缓解型多发性硬化（MS） 硬化症（RRMS）占所有MS病例的85%。虽然RRMS的确切病理学尚不清楚， 据了解，它与遗传和环境因素有关， 因素是微生物组。最近的证据表明，MS患者的肠道微生物群不同于 这表明它可能在病理生物学中发挥作用。然而，口头的重要性 微生物组，这是第二个最多样化的微生物组（第一个是肠道），作为潜在的环境 因素知之甚少。先前对口腔微生物组的研究表明，它不仅会影响我们的口腔， 我们的健康，我们的系统健康。事实上，其他神经退行性疾病和自身免疫性疾病也存在联系 口腔微生物群失调包括阿尔茨海默氏症、动脉粥样硬化和类风湿性关节炎。因此 有必要将口腔微生物组作为MS病理生物学中的环境因素进行研究 这个提议将填补这一知识空白。为了验证这一假设，我们将分析 来自50名RRMS患者和50名健康对照（HC）的生物标本。这种横向比较将 看看两者在微生物组成及其相关功能方面的差异和相似之处 组此外，由于代谢组影响宿主健康，微生物组可以影响宿主 代谢组学，我们将利用非靶向代谢组学方法来确定MS和HC口服 代谢物不同。最后，我们将把微生物和代谢物联系起来，以确定它们之间的关系。 口腔微生物组和宿主代谢物，并利用机器学习来识别最重要的 与MS的病理生物学相关的特征。总体而言，这项研究将有助于确定特定的口腔 微生物、微生物功能途径和宿主代谢途径，可用作潜在的 诊断生物标志物以及RRMS患者的治疗剂。