Tai Chi and Gut Microbiota in Metabolic Osteoarthritis

项目总结 骨关节炎(OA)是一个重大的公共卫生问题，会导致长期的疼痛、残疾和巨大的医疗费用，因此存在着巨大的治疗缺口。OA与代谢综合征密切相关的表现及其共同的病理生理学基础是通过先天免疫途径激活全身炎症，这预示着人们认识到与持续性疼痛相关的高度普遍的“代谢”OA表型。与代谢综合征一致的是，有证据表明肠道微生物群与OA疼痛的发生和严重程度相互作用，这是通过肠道微生物群的先天免疫激活来调节的。一项基于人群的大型队列研究进一步证明了肠道微生物区系变化的相关性，特别是链球菌种类的相对丰度和数量的增加与骨关节炎相关的膝关节疼痛。这些观察表明，可能存在通过以微生物组为靶标来影响OA的自然历史的机会；并通过研究其对疼痛通路中的微生物组的影响来更好地理解OA有效干预的生物学。 随机试验表明，太极，一种多维度的身心锻炼，在3到12个月或更长时间内对骨性关节炎有好处。然而，对潜在机制的有限了解限制了这种有前途的心身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治疗骨性关节炎疼痛的机制基础。本探索性研究的目的是确定太极心身锻炼对代谢性骨关节炎患者肠道微生物区系的影响，并估计其影响大小。我们将随机选择符合美国风湿病学会膝关节骨性关节炎标准的80名符合条件的受试者，进行为期12周的太极或健康教育干预。使用粪便DNA样本的16S rRNA扩增序列，我们将比较肠道微生物区系(组成、相对和差异丰度、α和β多样性)的变化(使用16S rRNA基因扩增序列)和链球菌数量的变化(使用定量PCR10)，以及它们与临床结果的关系。这项建议将为太极心身疗法治疗代谢性骨性关节炎的机制提供关键的初步知识。这些结果对于指导未来研究的设计是必要的，以阐明太极、肠道微生物区系、疼痛和行为路径之间的机制相互作用，这些路径潜在的心身方法的疾病修正作用，最终促进关节炎的治疗。

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.