Is the gut important in multiple joint osteoarthritis? A multimodal investigation in humans and pet dogs

肠道在多关节骨关节炎中重要吗？

• 批准号: 10859955
• 负责人: Duncan Lascelles
• 金额: $ 54.95万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-07 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10859955
• 关键词: Acceleration; Administrative Supplement; Age; Analgesics; Area; Arthralgia; Attention; Automobile Driving; Biological; Biological Markers; Biological Sciences; Breeding; CCL2 gene; Canis familiaris; Cartilage; Cessation of life; Clinical; Collagen; Complement; Complement component C1r; Complex; Data; Data Analyses; Data Set; Degenerative polyarthritis; Development; Dimensions; Disease; Enrollment; Ethnic Origin; Etiology; Generations; Goals; Human; Hyperalgesia; IL6 gene; Individual; Interleukin-1 beta; Intestinal permeability; Investigation; Joints; Knee; Knee Osteoarthritis; Leaky Gut; Lipopolysaccharides; Machine Learning; Macrophage Inflammatory Protein-1; Measures; Methods; Mission; Modeling; Molecular; Musculoskeletal Diseases; Musculoskeletal Pain; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Non-Steroidal Anti-Inflammatory Agents; Pain; Pain Measurement; Pain Research; Pain management; Parents; Pathway interactions; Patient Care; Patients; Pharmacotherapy; Phenotype; Population; Proteins; Race; Rheumatism; Role; Sampling; Serum; Severities; Severity of illness; Spinal Ganglia; Strategic Planning; Structure; Study of serum; Techniques; Therapeutic; Vitamin D-Binding Protein; Work; advanced analytics; analytical method; analytical tool; burden of illness; chronic pain; clinical phenotype; cohort; complex data; experience; gut dysbiosis; gut microbiome; individual variation; innovation; interest; lipopolysaccharide-binding protein; machine learning method; microbiome; mouse model; multimodality; neoantigens; novel; novel marker; novel therapeutics; opioid overdose; osteoarthritis pain; parent project; population based; potential biomarker; radiological imaging; response; sex; side effect; specific biomarkers; synergism; therapeutic evaluation; treatment response

PROJECT SUMMARY The parent project (Is the gut important in multiple joint osteoarthritis? A multimodal investigation in humans and pet dogs, R01AR080733) integrates serum biomarkers and radiographic measures of the burden of the disease of OA with measures of intestinal permeability and microbiome assessments in both humans and dogs. It will significantly advance our understanding of the role of a hitherto ignored driving etiology in MJOA – altered intestinal permeability – and create a novel transspecies model platform for testing therapeutics. This proposed supplement effectively synergizes with the parent project by adding a focus on a clinically critical dimension – pain associated with multi-joint osteoarthritis (MJOA). Pain associated with OA is what patients care about. This supplement will generate data that will help us better understand the multiple factors that drive pain and uncover novel therapeutic opportunities. We will expand and enhance our existing innovative work to include novel biomarkers of pain and pain assays relevant to the pain experience in humans and in dogs. There are two core features of this integration and enhancement: 1) to extend the analysis of samples in already being collected to include promising serum biomarkers for musculoskeletal pain and enhance pain phenotyping in the human cohort; 2) to apply advanced analytical techniques to the entire data set (parent and supplemental data) allowing us to perform elegant and innovative pain phenotyping in relation to intestinal permeability, gut microbiome and burden of OA. To advance our understanding of musculoskeletal pain, we will use cutting-edge machine learning analytical approaches to understand how pain phenotype(s), microbiome enterotype(s) and biomarker endotype(s) vary together and individually to advance our understanding of the complex multi-modal and multi-dimensional pain experience of OA patients. This supplement proposal is not a stand-alone project, rather it enriches the parent project and expands the opportunities for discovery of potential pain therapeutic strategies. The combined expertise of the two PIs and teams (OA, musculoskeletal pain, application of machine learning) makes us ideally suited to perform the proposed work. Integrating the supplement work at this stage is fiscally efficient, and scientifically it will accelerate the generation of data to support new investigative strategies that will lead to a better understanding of how to mitigate musculoskeletal pain.

项目总结 母项目(肠道在多发性关节骨关节炎中重要吗？人类的多模式研究 和宠物狗，R01AR080733)集成了血清生物标志物和放射学测量的负担 骨性关节炎患者的肠道通透性和微生物群评估 狗。这将大大促进我们对迄今被忽视的驾驶病因学在MJOA中的作用的理解- 改变肠道通透性--并创建一种用于测试治疗药物的新型跨物种模型平台。这 建议的补充方案通过将重点放在临床上，有效地与父项目协同 关键维度-与多关节骨关节炎(MJOA)相关的疼痛。与骨关节炎相关的疼痛是 病人关心的是什么。本补充资料将生成数据，帮助我们更好地理解 驱动疼痛和发现新的治疗机会的因素。我们将扩大和提升我们现有的 创新工作，包括新的疼痛生物标记物和与疼痛体验相关的疼痛分析 人类和狗身上都有。此集成和增强有两个核心特性：1)扩展 对已经收集的样本进行分析，以包括有望用于肌肉骨骼疼痛的血清生物标志物 并增强人类队列中的疼痛表型；2)将先进的分析技术应用于整个 数据集(父数据和补充数据)，使我们能够在 与肠道通透性、肠道微生物区系及骨性关节炎负担的关系。增进我们对…的理解 肌肉骨骼疼痛，我们将使用尖端机器学习的分析方法来了解疼痛 表型(S)、微生物组肠型(S)和生物标志物内型(S)一起和单独变化以促进 我们对骨性关节炎患者复杂的多模式、多维度疼痛体验的理解。这 补充方案不是一个独立的项目，而是丰富了父项目并扩展了 发现潜在的疼痛治疗策略的机会。两个私人投资总监和 团队(办公自动化、肌肉骨骼疼痛、机器学习的应用)使我们非常适合执行 建议的工作。在这个阶段整合补充工作在财务上是有效的，从科学上讲，它将 加快生成数据以支持新的调查战略，从而实现更好的 了解如何减轻肌肉骨骼疼痛。

项目成果

Association of plasma microbial composition with a leaky gut in obesity-related osteoarthritis: An exploratory study.

• DOI: 10.1016/j.ocarto.2022.100317
• 发表时间: 2022-12
• 期刊: Osteoarthritis and cartilage open
• 作者: Arbeeva, Liubov;Azcarate-Peril, M. Andrea;Cui, Yang;Nelson, Amanda E.;Loeser, Richard F.
• 通讯作者: Loeser, Richard F.