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  3. Distinct effects of different Bacteroides strains on depressive-like behavior via a gut-Th1/Th17 cells-brain axis

Distinct effects of different Bacteroides strains on depressive-like behavior via a gut-Th1/Th17 cells-brain axis

  • Commun Biol. 2026 Jan 13;9(1):247. doi: 10.1038/s42003-026-09525-x.
Zhiyu Li 1 2 3,  Peilin Qin 1 2,  Zuoli Sun 1 2,  Liangkang Li 1 2,  Peng Liang 1 2,  Yimei Zhao 1 2,  Siyu Ren 1 2,  Gang Wang 4 5,  Jian Yang 6 7
Affiliations

Affiliations

  • 1 Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
  • 2 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
  • 3 The Fourth People's Hospital of Wuhu, Wuhu, Anhui Province, China.
  • 4 Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China. [email protected].
  • 5 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. [email protected].
  • 6 Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China. [email protected].
  • 7 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. [email protected].
PMID: 41530303 DOI: 10.1038/s42003-026-09525-x
Abstract

Extensive evidence links gut microbiota to the pathogenesis of major depressive disorder (MDD), yet the specific microbial species involved remain unclear. Here, we identify distinct roles of three Bacteroides species-B. uniformis, B. vulgatus, and B. thetaiotaomicron-in depression. B. uniformis increases susceptibility to depression in mice, significantly enhances Th17 cell differentiation in vivo and in vitro, and upregulates hippocampal IL-17A level. However, treatment with SR1001, a Th17 cell inhibitor, alleviates B. uniformis-induced depressive-like behaviors. Conversely, B. thetaiotaomicron and B. vulgatus attenuate depressive behaviors in mice, significantly suppresse the differentiation of Th1 and Th17 cells in vivo, and reduce the levels of hippocampal cytokines, including IL-17A, IFN-γ, and TNF-α. Clinical analyses reveal increased Th1 and Th17 cells in MDD patients, correlating with depression severity. B. uniformis is enriched in MDD fecal samples and positively associated with Th17 levels, whereas B. thetaiotaomicron showes an inverse correlation. Mechanistically, targeted metabolomic shows that B. uniformis reduces butyric acid and Cholesterol sulfate, whereas B. thetaiotaomicron increases butyric acid, propionic acid, and biotin, all of which are linked to Th1 and Th17 regulation. These findings highlight the role of Bacteroides species in depression via a gut-Th1/Th17 cells-brain axis, providing mechanistic insights and ideas for therapeutic strategies.

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