Nasal Staphylococcus aureus carriage promotes depressive behaviour in mice via sex hormone degradation
The human microbiome has a pronounced impact on human physiology and behaviour. Despite its unique anatomical connection to the brain, the role of the nasal microbiome in neurological diseases is understudied. Here, using human data and experiments in mice, we show that nasal Staphylococcus aureus is linked to depression. Nasal microbiome analyses revealed a positive correlation between depression scores and S. aureus abundance among patients with depression and healthy controls. Metabolomics of the nasal cavity showed decreased sex hormones, estradiol and testosterone in patients with depression versus controls. Nasal microbiota transplants from patients reproduced depression-like behaviour in mice with differential abundance of S. aureus. Further homology and mutational analysis uncovered an S. aureus sex hormone-degrading enzyme, 17b-hydroxysteroid dehydrogenase (Hsd12), which degraded testosterone and estradiol in mice, leading to lower levels of dopamine and serotonin in the murine brain. These findings reveal a nasal commensal that influences depressive behaviour and provides insights into the nose-brain axis.
Authors
- Yulin Song (ORCID: https://orcid.org/0000-0002-2391-7466)
- Kareemah Ni
- Yanan Wang (ORCID: https://orcid.org/0000-0002-8864-5609)
- Guoxiu Xiang
- Xiao Wei Sun (ORCID: https://orcid.org/0000-0002-2840-1880)
- Huoqing Luo (ORCID: https://orcid.org/0000-0002-2948-6775)
- Ping Miao (ORCID: https://orcid.org/0000-0003-1937-1736)
- Michaël Otto (ORCID: https://orcid.org/0000-0002-2222-4115)
- Wenlong Yang (ORCID: https://orcid.org/0000-0003-3139-2767)
- Yan Pan (ORCID: https://orcid.org/0000-0001-7277-6877)
- Qian Liu (ORCID: https://orcid.org/0000-0001-8897-5117)
- Ji Hu
- Ying Jian (ORCID: https://orcid.org/0000-0001-5185-2455)
- Na Zhao (ORCID: https://orcid.org/0000-0002-8417-7895)
- Yanli Luo (ORCID: https://orcid.org/0000-0002-6824-6686)
- Mengxin He
- Zhen Shen (ORCID: https://orcid.org/0000-0002-4056-3583)
- Min Li (ORCID: https://orcid.org/0000-0002-8571-2909)
- Tianchi Chen
- Chenfeng Ji (ORCID: https://orcid.org/0000-0002-4750-042X)
- Ke Xu (ORCID: https://orcid.org/0000-0002-8035-9843)
- Lei He (ORCID: https://orcid.org/0000-0003-4679-5462)
Institutions
- Shanghai Jiao Tong University (CN)
- Renji Hospital (CN)
- ShanghaiTech University (CN)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2025-09-22
- DOI
- https://doi.org/10.1038/s41564-025-02120-6
- Citations
- 6
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 4.84