肠道微生物群与抑郁症
肠道微生物组作为多发性硬化症患者抑郁症决定因素的作用
该项目的目的是确定特定肠道微生物组或肠道衍生代谢物是否与多发性硬化症 (pwMS) 患者的抑郁症相关。 从机制上讲,研究人员进一步假设 pwMS 中的抑郁症与具有 GABA 生成活性和/或抗炎特性的肠道细菌丰度减少有关。 确定 pwMS 中抑郁症的存在是否与特定的肠道微生物组、肠道衍生代谢物或外周血免疫特征相关。 研究人员将对 John L. Trotter MS 中心招募的临床稳定的 pwMS 进行横断面研究。 研究人员将使用神经疾病生活质量 (Neuro-Qol) 抑郁量表评估抑郁症的存在,该量表是 NIH 最近使用现代心理测量技术开发并在 pwMS 中验证的 Neuro-Qol 中的 13 个量表之一。
总共将招募 120 名 pwMS:根据 Neuro-Qol 抑郁量表,60 名患有抑郁症,60 名没有抑郁症。 在研究访问中,将要求每位参与者提供用于微生物组分析的粪便样本和用于外周血免疫分型的血液样本。 将收集潜在的混杂因素并将其视为分析中的协变量。 其中包括: 1) 残疾程度 (EDSS); 2) 用抗抑郁药和 DMT 治疗; 3) 为期 4 天的食物日记,以评估饮食构成; 4)体重和身高计算BMI; 5)疲劳; 6) 体力活动水平; 7)睡眠质量。
研究概览
详细说明
我们的总体假设是,特定的肠道微生物组或肠道衍生代谢物与 pwMS 的抑郁症有关。 从机制上讲,研究人员进一步假设 pwMS 中的抑郁症与具有 GABA 生成活性和/或抗炎特性的肠道细菌丰度减少有关。
目标 1。 确定 pwMS 中抑郁症的存在是否与特定的肠道微生物组、肠道衍生代谢物或外周血免疫特征相关。
研究人员将对 John L. Trotter MS 中心招募的临床稳定的 pwMS 进行横断面研究。 研究人员将使用神经疾病生活质量 (Neuro-Qol) 抑郁量表评估抑郁症的存在,该量表是 NIH 最近使用现代心理测量技术开发并在 pwMS 中验证的 Neuro-Qol 中的 13 个量表之一。 总共将招募 120 名 pwMS:根据 Neuro-Qol 抑郁量表,60 名患有抑郁症,60 名没有抑郁症。 在研究访问中,将要求每位参与者提供用于微生物组分析的粪便样本和用于外周血免疫分型的血液样本。 将收集潜在的混杂因素并将其视为分析中的协变量。 其中包括: 1) 残疾程度 (EDSS); 2) 用抗抑郁药和 DMT 治疗; 3) 为期 4 天的食物日记,以评估饮食构成; 4)调查者视力和身高计算BMI; 5)疲劳; 6) 体力活动水平; 7)睡眠质量。
瞄准 1A。 确定抑郁症是否与 pwMS 中的特定肠道微生物组或肠道衍生代谢物概况相关。
粪便样本将被处理用于微生物组测序和代谢组学表征。
瞄准 1B。 确定抑郁症是否与 pwMS 中特定的外周血免疫炎症特征相关。
将从每个参与者处获取外周血样本以执行:1) 外周血免疫细胞表型分析以表征主要免疫细胞亚群及其激活; 2) 细胞内细胞因子产生研究血液淋巴细胞和单核细胞的细胞因子产生概况。
目的 2. 量化有或没有抑郁症的 pwMS 中 GABA 的产生,并确定体外肠道微生物组-免疫系统的相互作用。
为此,研究人员将进行功能研究,以评估有或没有抑郁症的 pwMS 肠道微生物群产生 GABA 和调节免疫炎症反应的潜力。
瞄准 2A。 量化整个粪便中的 GABA 水平,特定的粪便细菌分离物和有或没有抑郁症的 pwMS 的血液。
研究人员将评估 pwMS 粪便和血液中的 GABA 水平。 此外,研究人员将测量从 pwMS 肠道微生物群中分离出的拟杆菌 ssp 产生的 GABA。
瞄准 2B。 评估整个粪便和来自 pwMS 的特定细菌种类对血液免疫细胞表型和细胞因子产生的影响。
研究人员将测试整个肠道微生物组或特定细菌(在目标 1 中确定为与 pwMS 抑郁症相关)如何调节免疫细胞功能。 来自健康供体的外周血单核细胞 (PBMC) 将在来自全粪便或从 pwMS 分离的感兴趣细菌的条件培养基中培养。 体外暴露后的 PBMC 表型和细胞因子产生将通过流式细胞术表征。
研究类型
注册 (预期的)
联系人和位置
学习联系方式
- 姓名:Laura Piccio, MD,PhD
- 电话号码:314-747-4591
- 邮箱:picciol@wustl.edu
学习地点
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Missouri
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Saint Louis、Missouri、美国、63110
- 招聘中
- Washington University in St Louis
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
取样方法
研究人群
描述
- 年龄≥18岁
- 根据 2017 年修订的 McDonald 标准诊断 RRMS 或进行性 MS
- 未经治疗或使用任何 MS DMT,只要它们在过去 3 个月内临床稳定
- 研究访视和样本采集前 3 个月内无抗生素治疗史
- 无其他自身免疫性疾病、慢性代谢性疾病(如 糖尿病)或条件(例如 怀孕),这会干扰我们将在粪便和血液样本中测量的参数。
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
干预/治疗 |
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Neuro-QoL 抑郁量表 T 分数 > 55
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Neuro-Qol 抑郁量表,使用 55 的 T 分数作为阈值
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Neuro-QoL 抑郁量表 T 值 < 55
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Neuro-Qol 抑郁量表,使用 55 的 T 分数作为阈值
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
肠道微生物组、肠道衍生代谢物和外周血免疫概况
大体时间:3年
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肠道微生物组将通过宏基因组测序来表征。
通过 LC-MS 进行的非靶向代谢组分析。
通过流式细胞术分析进行的外周血表型分析
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3年
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全粪便、特定粪便分离菌和血液中的 GABA 水平
大体时间:3年
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通过靶向 LC-MS 测量整个粪便中的 GABA 水平流式细胞术测量患有或不患有抑郁症的 MS 患者的整个粪便和特定细菌种类对血液免疫细胞表型和细胞因子产生的影响。
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3年
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合作者和调查者
调查人员
- 首席研究员:Laura Piccio, MD, PhD、Washington University School of Medicine
出版物和有用的链接
一般刊物
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