Metagenomic analysis of the gut microbiota in major depressive disorder with different antidepressant efficacy: A prospective cohort study.

BACKGROUNDMajor depressive disorder (MDD) is globally prevalent, with Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) as first-line treatment. However, 30 %-40 % of patients have inadequate response, and early identification is difficult. Gut microbiota contributes to MDD pathogenesis through the gut-brain axis, but baseline differences between responders and non-responders to SSRIs or SNRIs remain unclear.

METHODS82 MDD individuals were initially screened. However, due to issues with the drug administration and fecal sample availability, a total of 43 people were eventually included. Based on 3-month Hamilton Depression Rating Scale (HAMD-17) changes, 29 patients were responders (39.12 ± 15.79 years, 8 males), while 14 were non-responders (40.14 ± 17.28 years, 5 males). Baseline assessments encompassed Depression Anxiety scales, demographics, and fecal metagenomic analysis (taxonomic/functional annotation, and differential analysis of microbial species and pathways).

RESULTSBaseline demographic characteristics, lifestyle factors, and anxiety/depression scores were comparable. Non-responders had higher relative abundances of Bacteroidaceae and Bacteroide; LEfSe showed responders enriched Hungatella, Ligilactobacillus_ruminis, and non-responders enriched Anaerostipes, Bacteroides_faecis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis identified 246 differentially expressed KEGG Orthologies and 13 pathways, with the steroid biosynthesis pathway (map00100) being enriched in non-responders and the D-amino acid metabolism pathway (map00470) enriched in responders. The study has limitations: small sample size and it lacks direct mechanism validation.

CONCLUSIONSThe composition and functional pathways of gut microbiota exhibit significant differences between responders and non-responders to SSRIs or SNRIs among MDD patients, providing clues for the development of new treatment strategies.