菌群移植治疗纤维肌痛症患者临床效果和安全性研究：一项随机、对照研究

Clinical Efficacy and Safety of Feces Microbiota Transplantation in Patients with Fibromyalgia: A Randomized, Controlled Study

摘要:

目的 肠道菌群紊乱被认为是纤维肌痛症（Fibromyalgia Syndrome，FM）的主要病因之一，本研究为探究菌群移植(fecal microbiota transplantation，FMT)能否改善FM患者的临床症状。方法：选取上海市东方医院疼痛科门诊从2021年12月至2022年05月收治的50例FM患者进行随机对照研究，采用抽签法将患者随机分为分为菌群移植+药物治疗组（FMT组25例）和单纯药物治疗组（对照组25例）。在治疗后1周、1月、3月、6月和12月，分别对两组患者的数字评价量表（numerical rating scale，NRS），弥漫疼痛指数量表（Widespread Pain Index, WPI），症状严重积分（Symptom Severity, SS），医院焦虑抑郁量表(The Hospital Anxiety and Depress-ionor Scale, HADS)，匹兹堡睡眠质量指数量表（Pittsburgh sleep quality index ，PSQI）评分，同时检测血浆神经递质水平综合评估治疗效果。 结果 共45例受试者完成试验，菌群移植显著改善FM患者临床症状（疼痛治疗效果、睡眠及焦虑抑郁情况）。术后1个月内，FMT组NRS评分略低于对照组(P > 0.05)，术后3个月、6个月和12个月时NRS评分明显下降(P < 0.001)。FMT组在接受菌群移植治疗6个月和12个月后WPI和SS评分显著降低（P<0.001）； 在接受治疗6个月后，患者的情绪和睡眠质量方面也得到很大的改善。与对照组相比，FMT组在治疗6个月和12个月后HADS和PSQI评分显著降低（P<0.001）。治疗6个月后，FMT组5-HT和GABA水平显著增加（P<0.001），而谷氨酸水平显著降低（P<0.001）。治疗后6个月，对照组总有效率为56.5%，FMT组为90.9%，两组间差异有统计学意义(P<0.05)。FMT组患者在静脉麻醉后，出现恶心和头晕的比率高于对照组，但两组无统计学差异。结论 FMT可有效改善FM的临床症状，FM与患者体内的神经递质关系十分密切，这可能成为FM患者的诊断标志物或全新治疗靶点。

Abstract:

Objective Intestinal flora disturbance is considered to be one of the main causes of fibromyalgia syndrome (FM). This study aims to explore whether fecal microbiota transplantation (FMT) could improve the clinical symptoms of patients with FM. Methods 50 FM patients were enrolled in this randomized controlled study, in which patients were randomly assigned to FMT + drug treatment group (FMT group, 25 cases) or drug treatment group (control group, 25 cases) by drawing lots. The Numerical Rating Scale (NRS), Widespread Pain Index (WPI), Symptom Severity (SS), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep quality (PSQI) scores of the two groups were evaluated at 1 week, 1 month, 6 months and 12 months after treatment, and the plasma neurotransmitter levels were detected to comprehensively evaluate the treatment effect. Results A total of 45 patients completed the trial, and the results showed that FMT significantly improved the clinical symptoms (including the therapeutic effects of pain, sleep, anxiety and depression) of FM patients. Within 1 months after treatment, the NRS score of the FMT group was slightly lower than that of the control group (P>0.05), the NRS scores decreased significantly at 3, 6 and 12 months after treatment (P<0.001). The WPI and SS scores decreased significantly in the FMT group after 6 and 12 months of treatment (P<0.001); After 6 months of treatment, the patients' mood and sleep quality also improved greatly. Compared with the control group, the FMT group had significantly lower HADS and PSQI scores after 6 and 12 months of FMT treatment (P<0.001). After 6 months of treatment, 5-HT and GABA levels significantly increased in the FMT group (P<0.001), while glutamate levels significantly decreased in the FMT group (P<0.001). After 6 months of treatment, the total effective rate was 56.5% in the control group and 90.9% in the FMT group, and the difference between the two groups was statistically significant (P< 0.05). After intravenous anesthesia, the FMT group had a higher rate of nausea and dizziness than the control group, but there was no statistically significant difference between the two groups. Conclusion FMT can effectively improve the clinical symptoms of FM, and there are close relations between the change of neurotransmitters and FM, which indicates that certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.