We investigated alterations in the intestinal microbiota of patients with temporal lobe epilepsy (TLE) and their associations with drug resistance and psychiatric comorbidities. Thirty TLE patients and 30 family-matched healthy controls sharing the same household diet were recruited, and fecal samples were analyzed by high-throughput 16S rDNA sequencing on the Illumina MiSeq \(2\times 300\) bp platform. Differential abundance was assessed using Metastats and LEfSe with Benjamini–Hochberg false-discovery-rate correction, and independently validated using ANCOM-BC to account for the compositional nature of microbiome data. Community \(\alpha\) - and \(\beta\) -diversity indices showed no significant differences between groups; however, ANCOM-BC identified species-level signatures in drug-resistant epilepsy, including significant depletion of Bacteroides plebeius and Coprococcus comes. Among psychiatric subgroups, Ruminococcus was significantly reduced in patients with comorbid depression, while Bilophila was enriched in those with comorbid anxiety and depression. Bacteroides stercoris distinguished the anxiety-plus-depression subgroup from the depression-only subgroup with robust support from both ANCOM and ANCOM-BC. Given the modest overall sample size ( \(n=30\) per arm) and small psychiatric and drug-resistance subgroups, these findings should be regarded as exploratory and hypothesis-generating associations rather than definitive biomarkers. They identify candidate microbial taxa warranting validation in larger, longitudinal cohorts combined with metagenomic and metabolomic approaches.
