Tai Chi and Gut Microbiota in Metabolic Osteoarthritis

太极拳和代谢性骨关节炎中的肠道微生物群

• 批准号: 10615704
• 负责人: CHENCHEN WANG
• 金额: $ 22.17万
• 依托单位: TUFTS 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: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615704
• 关键词: 16S ribosomal RNA sequencing; Address; Adult; Affect; Age; American; Analysis of Variance; Arthritis; Behavioral; Biology; Body mass index; Central Nervous System; Clinical; Clinical Trials; Cohort Studies; Complex; DNA; Degenerative polyarthritis; Dimensions; Discriminant Analysis; Disease; Ecology; Education; Educational Intervention; Eligibility Determination; Exercise; Exhibits; Future; Gender; Goals; Health Care Costs; Immune system; Individual; Intervention; Joints; Knee Osteoarthritis; Knowledge; Link; Measures; Mediating; Medical Care Costs; Metabolic; Metabolic syndrome; Mind-Body Intervention; Moderate Exercise; Moods; Movement; Multivariate Analysis; Natural History; Outcome; Pain; Participant; Pathogenesis; Pathway interactions; Patients; Persistent pain; Procedures; Public Health; Quality of life; Randomized; Relaxation; Research; Rheumatology; Role; Sampling; Severities; Streptococcus; Tai Ji; Testing; Therapeutic; Vegan Diet; Western Ontario and McMaster Universities Arthritis Index; attentional control; beta diversity; clinical efficacy; clinical implementation; college; design; disability; disease phenotype; effective intervention; experience; follow-up; gut microbiome; gut microbiota; gut-brain axis; hypothalamic-pituitary-adrenal axis; illness length; immune activation; improved; innate immune pathways; innovation; insight; knee pain; metabolic phenotype; metagenomic sequencing; microbial; microbiome; microbiota; microbiota profiles; mind body interaction; mind/body; osteoarthritis pain; pain processing; pain score; population based; psychosocial; randomized trial; response; stress reduction; systemic inflammatory response; theories

PROJECT SUMMARY Osteoarthritis (OA) is a major public health problem and leads to long-term pain, disability, and huge healthcare costs, for which there is a substantial therapeutic gap. The closely linked manifestations of OA with metabolic syndrome and its shared pathophysiological basis in activation of systemic inflammation through innate immune pathways, have predicated recognition of a highly prevalent ‘metabolic’ phenotype of OA that is associated with persistent pain. Consonant with metabolic syndrome, there is evidence for the interaction of the gut microbiome with occurrence and severity of OA pain that is mediated through innate immune activation by gut microbial flora. A large population-based cohort study further demonstrates an association of alterations in gut microbiota, specifically an increase in the relative abundance and quantity of Streptococcus species with osteoarthritis-related knee pain. These observations suggest that opportunities may exist to influence the natural history of OA by targeting the microbiome; and to better understand the biology of effective interventions of OA by studying their effects on the microbiome in the context of pain pathways. Randomized trials have demonstrated that Tai Chi, a multi-dimensional mind-body exercise, shows benefits for OA for 3 to 12 months or longer. However, limited knowledge of the underlying mechanisms has restricted further optimization of the clinical efficacy and implementation of this promising mind-body therapy. Our long-term goal is to elucidate the mechanistic basis of the effect of Tai Chi in treating OA pain. The aim of this exploratory study is to determine the effect of Tai Chi mind-body exercise on gut microbiota in patients with metabolic OA and estimate the effect size. We will randomize 80 eligible individuals who meet the American College of Rheumatology criteria for knee OA into Tai Chi or wellness education interventions for 12 weeks. Using 16S rRNA amplicon sequencing of fecal DNA samples we will compare the changes in gut microbiota profiles (composition, relative and differential abundance, alpha and beta diversity) using 16S rRNA gene amplicon sequencing, and quantity of Streptococcus species using quantitative PCR10, as well as their association with clinical outcomes. This proposal will provide crucial preliminary knowledge of the mechanism underlying Tai Chi mind-body therapy for metabolic OA. These results are necessary to guide the design of future studies to elucidate mechanistic interactions between Tai Chi, gut microbiota, pain and behavioral pathways underlying the potential disease-modifying role of mind-body approaches, ultimately advancing arthritis treatment.

项目概要 骨关节炎（OA）是一个重大的公共卫生问题，会导致长期疼痛、残疾和巨大的医疗费用，而治疗缺口巨大。 OA 与代谢综合征密切相关的表现及其通过先天免疫途径激活全身炎症的共同病理生理学基础，预示着对与持续性疼痛相关的高度普遍的 OA“代谢”表型的认识。与代谢综合征相一致，有证据表明肠道微生物群与 OA 疼痛的发生和严重程度存在相互作用，这种相互作用是通过肠道微生物菌群激活先天免疫介导的。一项基于人群的大型队列研究进一步证明了肠道微生物群的改变，特别是链球菌物种相对丰度和数量的增加与骨关节炎相关的膝盖疼痛之间的关联。这些观察结果表明，可能存在通过针对微生物组来影响 OA 自然史的机会；通过研究疼痛通路中微生物组的影响，更好地了解 OA 有效干预措施的生物学。 随机试验表明，太极拳是一种多维身心锻炼，对 OA 具有持续 3 至 12 个月或更长时间的益处。然而，对潜在机制的了解有限，限制了这种有前途的身心疗法的临床疗效和实施的进一步优化。我们的长期目标是阐明太极拳治疗骨关节炎疼痛的机制基础。这项探索性研究的目的是确定太极身心锻炼对代谢性 OA 患者肠道微生物群的影响并估计影响大小。我们将随机抽取 80 名符合美国风湿病学会膝关节 OA 标准的合格个体进行太极拳或健康教育干预，为期 12 周。通过粪便 DNA 样本的 16S rRNA 扩增子测序，我们将使用 16S rRNA 基因扩增子测序来比较肠道微生物群概况（组成、相对和差异丰度、α 和 β 多样性）的变化，并使用定量 PCR10 来比较链球菌种类的数量，以及它们与临床结果的关联。该提案将为太极身心疗法治疗代谢性骨关节炎的机制提供重要的初步了解。这些结果对于指导未来研究的设计是必要的，以阐明太极拳、肠道微生物群、疼痛和行为途径之间的机制相互作用，这些相互作用是身心方法潜在的疾病缓解作用的基础，最终推进关节炎的治疗。