Gut microbiota characteristics and targeted tryptophan metabolomics in premature ejaculation patients with depressive state: a cross-sectional study

Background: The gut microbiota-tryptophan metabolic axis has emerged as a potential modulator of neuropsychiatric disorders, yet its role in premature ejaculation (PE) comorbid with depressive states remains unexplored. Methods: Fifteen eligible PE patients were enrolled. Depressive status was assessed using the Patient Health Questionnaire-9 (PHQ-9), dividing participants into a depressive-state group (n = 9) and a non-depressive group (n = 6). Demographic and clinical data, including age, body mass index (BMI), International Index of Erectile Function-5 (IIEF-5), Premature Ejaculation Diagnostic Tool (PEDT) scores, total testosterone (TT), and free testosterone (FT) levels, were recorded. Fecal samples underwent 16S rRNA sequencing for gut microbiota profiling, while serum samples were subjected to targeted tryptophan metabolomic analysis. Associations between gut microbiota and tryptophan metabolites were evaluated using Spearman’s correlation. Results: The depressive-state group exhibited a significantly higher abundance of Desulfobacterota (phylum level: relative abundance 0.12% vs. 0.08%, p = 0.04; absolute abundance 5.9 × 106 vs. 2.1 × 105 copies/g, p = 0.007) and lower serum kynurenic acid (KYNA) levels (0.005 ± 0.002 vs. 0.009 ± 0.003 µg/mL, p = 0.006) compared to the non-depressive group. A significant negative correlation was observed between Desulfobacterota abundance and KYNA levels (r = −0.66, p = 0.016). Conclusions: PE patients with depressive states demonstrate altered gut microbiota features—characterized by elevated Desulfobacterota abundance at multiple taxonomic levels—and suppressed serum KYNA concentrations, which are inversely correlated. These findings suggest that depressive status may disturb gut microbiota-tryptophan metabolic interactions, highlighting its potential as a therapeutic target for personalized PE management. Clinical Trial Registration: https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2400079838, ChiCTR2400079838.