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; 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.

项目摘要 骨关节炎（OA）是一个重大的公共卫生问题，导致长期疼痛，残疾和巨大的医疗费用，存在巨大的治疗差异。 OA与代谢综合征的紧密相关表现及其通过先天免疫途径激活全身性炎症的共同病理生理基础，预测了与持续性疼痛相关的高度普遍的OA的“代谢”表型。与代谢综合征辅音有关，有证据表明肠道微生物组与OA疼痛的发生和严重程度的相互作用，这是通过肠道微生物菌群的先天免疫激活介导的。一项大型基于人群的队列研究进一步证明了肠道微生物群的改变，特别是增加了与骨关节炎相关的膝关节疼痛的链球菌物种的相对丰度和数量增加。这些观察结果表明，可能存在机会通过靶向微生物组来影响OA的自然历史。并通过在疼痛途径的背景下研究其对微生物组的影响，以更好地了解OA有效干预措施的生物学。 随机试验表明，Tai Chi是一种多维思维体育练习，显示了OA的好处3至12个月或更长时间。但是，对基本机制的有限了解限制了对这种承诺思维疗法的临床有效性的进一步优化。我们的长期目标是阐明太极汽车在治疗OA疼痛方面的作用的机械基础。这项探索性研究的目的是确定Tai Chi心理运动对肠道微生物群对代谢OA患者的影响并估计效果大小。我们将随机将符合美国风湿病学院膝盖OA学院的80个合格的个人进入Tai Chi或健康教育干预措施12周。使用粪便DNA样品的16S rRNA扩增测序，我们将使用16S rRNA gene gene amplicon测序，使用定量PCR10的链球菌物种的数量来比较肠道微生物群（组成，相对和差异丰度，α和β多样性）的变化。该提案将提供有关代谢OA的TAI CHI心理治疗机制的重要初步知识。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械相互作用，这是思维方法方法的潜在疾病调整作用的基础，并最终提高关节炎治疗。