Abstract
This study aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) as an adjunctive therapy for depressive episodes. This study recruited 46 participants aged 18–65 from January 2022 to December 2023 who were diagnosed with depression according to the International Classification of Diseases, 10th edition. They were randomly divided into two groups to receive different treatments, including FMT combined with medication group (test group, n = 23) and the medication-only group (control group, n = 23). Assessments were performed before and two weeks after treatment. Ten predominant gut microbiota species were analyzed, and the Hamilton’s Depression Scale-24(HAMD-24) was used to evaluate depressive symptoms. Adverse events related to treatment were assessed using an adverse event scale and laboratory tests. The main evaluation indicators included the reduction rate of HAMD-24 scores, treatment efficacy rate, and changes in the indicators of the ten predominant intestinal bacteria before and after transplantation. Safety assessment indicators included adverse events, blood routine, biochemistry, electrocardiogram, immunological parameters (immunoglobulins and complement), hypersensitive C-reactive protein(hs-CRP), thyroid function, and glycated hemoglobin. The rank-sum test was performed to compare differences in microbiota before and after FMT treatment. The relationship between gut microbiota and depression severity was examined by means of correlation analysis. The baseline HAMD-24 scores showed no significant difference between the test and control groups (P > 0.05). After two weeks treatment, the reduction in HAMD-24 scores (P = 0.048) and the HAMD-24 reduction rate (P = 0.016) were significantly higher in the test group than control group (P < 0.05). Following FMT treatment, Enterococcus, Lactobacillus, Bifidobacterium, and Butyricicoccus levels significantly increased compared to baseline (P < 0.05). Linear discriminant analysis(LDA) revealed a significant post-treatment increase in Enterococcus relative abundance (P = 0.02). In the test group, baseline-enriched Clostridium prausnitzii (P = 0.040), Butyricicoccus (P = 0.029), and Eubacterium rectale (P = 0.004) showed significant negative correlations with HAMD-24 scores, whereas post-treatment Enterococcus was correlated with HAMD-24 scores (P = 0.030). Adverse event incidence was 28.6% in the test group and 30% in the control group, with no significant difference (P = 0.928). Reported discomforts during FMT treatment—nausea, vomiting, and nasopharyngeal discomfort—were mild and self-resolving, with no serious adverse events observed. The administration of FMT as an adjunctive therapy demonstrates superior improvement in depressive symptoms and is deemed safe with no apparent adverse reactions. There was no change in the composition of gut microbiota structure before and after FMT in patients with depression. Enterococcus showed a significant relative abundance increase in the gut after FMT. The post-treatment Enterococcus was correlated with HAMD-24 scores. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-41801-y.