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The emerging role of the gut microbiome in depression: implications for precision medicine

Molecular Psychiatry (2025)Cite this article

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Abstract

Major depressive disorder is a debilitating mental illness that seriously endangers human health. Its pathogenesis is highly complex, and traditional treatments face substantial challenges. A growing body of preclinical and clinical findings highlight the important role of the gut microbiome in the pathogenesis of depression and its potential as a diagnostic and therapeutic target. A deeper understanding of how the gut microbiome regulates depression will greatly enhance its clinical application, improve diagnostic and treatment strategies, and pave the way for microbiota-based precision medicine for depression. In this review, we summarize the depression-associated compositional and functional microbial alterations, delineate their mechanistic contributions to disease pathogenesis, and evaluate their potentiality as novel diagnostic biomarkers and treatment targets. Finally, we consider the future potential of utilizing the gut microbiome to advance precision medicine approaches for depression.

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Fig. 1: The impact of the gut microbiome on the pathogenesis of depression.
Fig. 2: The potential microbiota-based interventions for depression.
Fig. 3: The role of the gut microbiome in antidepressants treatment strategies.

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Acknowledgements

This work was supported by grants from the Natural Science Foundation Project of China (82201683, 82401814 and 82401789), the Natural Science Foundation of Chongqing (CSTB2024NSCQ-MSX0649), and the Joint Project of Chongqing Municipal Science and Technology Bureau and Chongqing Health Commission (2023CCXM003).

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  1. These authors contributed equally: Lanxiang Liu, Haiyang Wang.

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  1. Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China

    Lanxiang Liu & Peng Xie

  2. Department of Neurology, NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Lanxiang Liu, Haiyang Wang, Siyi Guo, Sifang Liu, Yamei Du, Lian Wang, Dian He, Xiaolong Mo, Hanping Zhang, Qisheng Cheng, Rui Xiao & Peng Xie

  3. Faculty of Basic Medicine, Department of Pathology, Chongqing Medical University, Chongqing, China

    Rui Xiao

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LXL, HYW, and PX conceived the idea for the review. SFL, LW, XLM, QSC, and RX searched the literature and extracted relevant information. LXL, YMD, and DH designed and prepared the figures and tables. LXL and HYW originally drafted the manuscript. SYG and HPZ reviewed the original draft and provided feedback to further improve the manuscript. LXL, HYW, HPZ, and PX acquired the funding. All authors reviewed the final version of the manuscript and approved the submission in its present form.

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Liu, L., Wang, H., Guo, S. et al. The emerging role of the gut microbiome in depression: implications for precision medicine. Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-03191-x

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