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粪菌移植在甲氨蝶呤应答不足类风湿关节炎患者中疗效与机制的初步探索

李蓉 徐浩杰 聂玉雪 李玥 赵丽丹

中华临床免疫和变态反应杂志2026,Vol.20Issue(1):1-10,10.
中华临床免疫和变态反应杂志2026,Vol.20Issue(1):1-10,10.DOI:10.3969/j.issn.1673-8705.2026.01.001

粪菌移植在甲氨蝶呤应答不足类风湿关节炎患者中疗效与机制的初步探索

Pilot study offecal microbiota transplantation in rheumatoid arthritis with inadequate re-sponse to methotrexate

李蓉 1徐浩杰 2聂玉雪 1李玥 3赵丽丹1

作者信息

  • 1. 100730 北京,中国医学科学院北京协和医学院北京协和医院罕见病医学科,疑难重症及罕见病国家重点实验室,中国医学科学院北京协和医院风湿免疫科,国家皮肤与免疫疾病临床医学研究中心,风湿免疫病学教育部重点实验室
  • 2. 100044 北京,北京大学人民医院风湿免疫科
  • 3. 100730 北京,中国医学科学院北京协和医学院北京协和医院罕见病医学科,疑难重症及罕见病国家重点实验室,中国医学科学院北京协和医院消化内科
  • 折叠

摘要

Abstract

Objective To evaluate the efficacy and safety of fecal microbiota transplantation(FMT)in rheumatoid arthritis(RA)patients with inadequate response to methotrexate(MTX),and explore the under-lying mechanism via multi-omics.Methods RA patients with inadequate response and active disease under MTX treatment for at least 3 months received 7 doses(30 capsules/dose)of oral lyophilized FMT capsules prepared from health donors,while maintaining previous MTX treatment.During a 24 week follow-up,ACR re-sponses,changes of disease activities(evaluated with DAS28,CDAI,SDAI),inflammatory indices(meas-ured by ESR,CRP)were evaluated at week 8,16 and 24.Fecal and serum samples were collected at each visit and used for 16S rRNA sequencing and untargeted LC-MS metabolomics.Results Two male patients were recruited and finished all FMT sessions and visits.By week 16,both patients achieved ACR 50 and ACR 70,respectively.DAS28-ESR,CRP,ESR,visual analogue scale of pain,and functional scores(HAQ)all showed improvement.No serious adverse events occurred.After FMT,α-diversity of intestinal microbiota in-creased with the changes of phylum composition.By week 16,the ratio of Bacteriodota/Firmicutes en-hanced.Serum metabolomics indicated the remodeling of amino acid,indole,and lipid metabolism path-ways.Conclusions FMT add-on helped reduce disease activity with good tolerability in RA patients with inad-equate response to MTX treatment.Gut microbiota remodeling accompanied with lipid and tryptophan metabo-lism alteration were observed.

关键词

类风湿关节炎/粪菌移植/甲氨蝶呤/多组学分析

Key words

rheumatoid arthritis/fecal microbiota transplantation/methotrexate/multi-omics analysis

引用本文复制引用

李蓉,徐浩杰,聂玉雪,李玥,赵丽丹..粪菌移植在甲氨蝶呤应答不足类风湿关节炎患者中疗效与机制的初步探索[J].中华临床免疫和变态反应杂志,2026,20(1):1-10,10.

基金项目

国家自然科学基金(82071840) (82071840)

中国医学科学院医学与健康科技创新工程(2020-I2M-C&T-B-013) (2020-I2M-C&T-B-013)

中央高水平医院临床科研基金(2022-PUMCH-A-108) National Natural Science Foundation of China(82071840) (2022-PUMCH-A-108)

CAMS Innovation Fund for Medical Sciences(2020-I2M-C&T-B-013) (2020-I2M-C&T-B-013)

National High Level Hospital Clinical Research Funding(2022-PUMCH-A-108) (2022-PUMCH-A-108)

中华临床免疫和变态反应杂志

1673-8705

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