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OA

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.