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

B. uniformis increases susceptibility to depressive-like behavior in mice.

• B. uniformis colonization significantly enhanced depressive-like behaviors in mouse models.
• Treatment with SR1001, a Th17 cell inhibitor, alleviated B. uniformis-induced depressive-like behaviors, indicating the effect is Th17-dependent.
• B. uniformis significantly enhanced Th17 cell differentiation both in vivo and in vitro.
• B. uniformis upregulated hippocampal IL-17A levels.

B. thetaiotaomicron and B. vulgatus attenuate depressive-like behaviors in mice.

• Both species significantly suppressed the differentiation of Th1 and Th17 cells in vivo.
• Both species reduced levels of hippocampal cytokines including IL-17A, IFN-γ, and TNF-α.
• B. thetaiotaomicron showed an inverse correlation with Th17 levels in clinical samples.
• Effects were observed in mouse models of depression.

MDD patients exhibit increased Th1 and Th17 cells that correlate with depression severity.

• Clinical analyses revealed increased Th1 and Th17 cells in MDD patients compared to controls.
• Th1 and Th17 cell levels positively correlated with depression severity in MDD patients.
• B. uniformis was enriched in MDD fecal samples and positively associated with Th17 levels.
• B. thetaiotaomicron showed an inverse correlation with Th17 levels in MDD patients.

B. uniformis and B. thetaiotaomicron exert opposing effects on gut metabolites linked to Th1/Th17 regulation.

• Targeted metabolomics showed that B. uniformis reduces butyric acid and cholesterol sulfate.
• B. thetaiotaomicron increases butyric acid, propionic acid, and biotin.
• These metabolites are linked to Th1 and Th17 immune cell regulation.
• The mechanistic pathway was identified as a gut-Th1/Th17 cells-brain axis.

B. uniformis is enriched in fecal samples from MDD patients.

• Clinical fecal sample analyses demonstrated enrichment of B. uniformis in MDD patients.
• B. uniformis abundance positively associated with Th17 cell levels in MDD patients.
• This finding links the preclinical mouse data to human MDD pathology.
• B. thetaiotaomicron showed an inverse (negative) correlation pattern compared to B. uniformis in clinical samples.

The gut microbiota influences depression through a gut-Th1/Th17 cells-brain axis involving specific Bacteroides species.

• Three distinct Bacteroides species—B. uniformis, B. vulgatus, and B. thetaiotaomicron—were identified as having distinct roles in depression.
• The mechanism involves modulation of peripheral Th1/Th17 immune cell differentiation and subsequent changes in hippocampal cytokine levels.
• The findings provide mechanistic insights connecting specific gut bacteria, immune cell populations, and brain inflammation in depression.
• Results suggest Bacteroides species as potential therapeutic targets for MDD.