菌群移植治疗纤维肌痛临床效果和安全性研究:一项随机对照研究

Clinical efficacy and safety of fecal microbiota transplantation in patients with fibromyalgia:a randomized controlled study

目的:肠道菌群紊乱被认为是纤维肌痛(fibromyalgia,FM)的主要病因之一,本研究探究菌群移植(fecal microbiota transplantation,FMT)能否改善FM病人的临床症状。方法:选取上海市东方医院疼痛科门诊从2021年12月至2022年5月收治的50例FM病人进行随机对照研究,采用抽签法将病人随机分为菌群移植+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个月、3个月、6个月和12个月分别评估两组病人疼痛数字分级评分法(numerical rating scale,NRS)评分、弥漫性疼痛指数(widespread pain index,WPI)、症状严重度评分(symptom severity,SS)、医院焦虑抑郁量表(hospital anxiety and depression scale,HADS)、匹兹堡睡眠质量指数(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,FMT可显著改善FM病人临床症状(疼痛治疗效果、睡眠及焦虑抑郁情况)。术后1个月内,FMT组NRS评分与对照组相比差异无统计学意义,术后3个月、6个月和12个月时FMT组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,FMT组病人的情绪和睡眠质量也得到很大改善。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-羟色胺(5-hydroxytryptamine,5-HT)和γ-氨基丁酸(γ-aminobutyric acid,GABA)水平显著增加(P<0.001),而谷氨酸(glutamic acid,Glu)水平显著降低(P<0.001)。治疗6个月后,对照组总有效率为56.5%,FMT组为90.9%(P<0.05)。两组病人术后第1天不良反应发生率差异无统计学意义。结论:FMT改变FM病人体内疼痛相关神经递质水平,有效改善FM的临床症状,这可能成为FM病人的全新治疗靶点。

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:Fifty FM patients were enrolled in this randomized controlled study,and all 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 index(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 month after treatment,there was no significant difference in NRS scores between FMT group and control group,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-hydroxytryptamine(5-HT)andγ-aminobutyric acid(GABA)levels significantly increased in the FMT group(P<0.001),while glutamic acid(Glu)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).There was no significant difference in the incidence of adverse reactions on the first postoperative day between the two groups.Conclusion:FMT changes the level of pain-related neurotransmitters in FM patients and effectively improves the clinical symptoms of FM,which may become a new therapy target for FM patients.