This cross-sectional study investigated the association between gut microbiota dysbiosis and the severity of major depressive disorder (MDD). Shotgun metagenomic profiling of stool samples from 138 MDD patients and 155 healthy controls revealed that microbial diversity was closely related to MDD severity. *Bacteroides* abundance was significantly increased in moderate and severe MDD, while *Ruminococcus* and *Eubacterium* were depleted mainly in the severe group. Ninety-nine bacteria species were identified as specific to depression severity, and a panel of 37 bacterial species effectively distinguished MDD patients with different severities. The study identified different gut microbiota perturbation patterns in mild-to-severe depression, suggesting potential diagnostic and therapeutic targets.

Xi Hu, Yifan Li, Jing Wu, Hanping Zhang, Yu Huang, Xunmin Tan, Lu Wen, Xingyu Zhou, Peijun Xie, Oluwatayo Israel Olasunkanmi, Jingjing Zhou, Zuoli Sun, Min Liu, Guofu Zhang, Jian Yang, Peng Zheng, Peng Xie