首都医科大学

Clinical and Translational Report Adjunctive fecal microbiota transplantation for major depressive disorder: A randomized, double- blind, placebo-controlled trial Graphical abstract Highlights • Adjunctive oral FMT accelerates antidepressant response as early as week 2 • Superior efficacy persists through 8 weeks with no additional side effects • FMT reshapes gut microbes, with donor strains coexisting in recipients • Benefits are mediated by elevated bile acids and reduced systemic inflammation Authors Jing Li, Yaping Wang, Ruinan Li, ..., Jingjing Zhou, Jian Yang, Gang Wang Correspondence jingjingzhou@mail.ccmu.edu.cn (J.Z.), yangjian@ccmu.edu.cn (J.Y.), gangwangdoc@ccmu.edu.cn (G.W.) In brief Li et al. report that adjunctive oral fecal microbiota transplantation provides a rapid and sustained antidepressant response in patients with major depressive disorder. Multi-omics integration reveals that this clinical benefit is linked to successful donor strain engraftment, which subsequently modulates bile-acid metabolism and suppresses systemic inflammatory signaling. MDD patient (n=60) Placebo Group (n=30) FMT Group (n=30) Escitalopram (ESC) 0 2 4 6 8 A Symptom alleviation No Serious Adverse Event Safety & Tolerability Multi-omics analysis Oscillospiraceae Lachnospiraceae Metabolomics (Bile Acids) Glycodeoxycholic acid Glycocholic acid 0 2 week 8 C Array Fecal metagenomics Serum metabolomics m/zRe la tiv e ab un da nc e cytokines Blood RNA expression B Placebo FMT Placebo FMT * * 4 0 20 40 60 80 2 8 * 0.0668 FMT Placebo Glycodeoxycholic acid Oscillibacter sp_MM59 CCL19 Mediation: Glycodeoxycholic acid Adjusted for age, sex, BMI, smoke a = 0. 21 (p =0 .01 0) b = -0.18 (p =0.025) c’ = -0.18 (p =0.027) -15 -10 -5 0 Change of HAMD-17 Score Response Rate RNA Protein Activation IL-22RA1 CCL19 IL-6 IL-17A Placebo Group FMT GroupModulation Li et al., 2026, Cell Host & Microbe 34, 1–16 July 8, 2026 © 2026 The Authors. Published by Elsevier Inc. https://doi.org/10.1016/j.chom.2026.05.017 ll Clinical and Translational Report Adjunctive fecal microbiota transplantation for major depressive disorder: A randomized, double-blind, placebo-controlled trial Jing Li,1,6 Yaping Wang,1,6 Ruinan Li,1,6 Huanwei Huang,1,6 Xuequan Zhu,1,6 Xiaozheng Li,3 Zuoli Sun,1 Ling Zhang,1 Peng Zheng,4,5 Yi He,1 Jing Liu,1 Xueshan Zhang,1 Siyu Ren,1 Mingxia Liu,1 Haixia Wang,1 Yanting Luo,1 Fei Wang,1 Jingjing Zhou,1,* Jian Yang,1,2,7,* and Gang Wang1,2,* 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China 3College of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, China 4Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China 5NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China 6These authors contributed equally 7Lead contact *Correspondence: jingjingzhou@mail.ccmu.edu.cn (J.Z.), yangjian@ccmu.edu.cn (J.Y.), gangwangdoc@ccmu.edu.cn (G.W.) https://doi.org/10.1016/j.chom.2026.05.017 SUMMARY Gut microbiota may influence antidepressant treatment outcomes, yet whether targeted modulation can enhance efficacy remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in pa- tients with major depressive disorder, administering a 2-week course of fecal microbiota transplantation (FMT) capsules or placebo as an adjunct to escitalopram (ChiCTR2300071421). Remission rates at week 8 did not differ significantly between groups, but FMT produced greater reductions in Hamilton Depression Rating Scale, 17-item version (HAMD-17) scores at weeks 2 and 8. FMT was well-tolerated with a safet