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Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity.

Mingliang Zhao1, Zhenxing Ren1, Aihua Zhao1

  • 1Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.

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Depleted gut bacteria like Bifidobacterium longum and Roseburia intestinalis are linked to depression. Restoring these microbes or their metabolite homovanillic acid (HVA) improved depressive symptoms in mice.

Keywords:
Bifidobacterium longumRoseburia intestinalisautophagic deathdepressionhomovanillic acidsynaptic integrity

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Area of Science:

  • Neuroscience
  • Microbiology
  • Gastroenterology

Background:

  • The gut-brain axis plays a role in depression, but mechanisms are unclear.
  • Specific gut bacteria and neurotransmitters are depleted in depression.

Purpose of the Study:

  • Investigate the role of Bifidobacterium longum and Roseburia intestinalis in depression.
  • Elucidate the mechanism by which gut microbiota influence neurotransmitter production and synaptic integrity.

Main Methods:

  • Compared gut microbiota and homovanillic acid (HVA) levels in individuals with depression and mouse models.
  • Administered HVA, B. longum, or R. intestinalis to mouse models of depression.
  • Analyzed the effect of HVA on synaptic autophagic death in hippocampal neurons.

Main Results:

  • Depleted B. longum and R. intestinalis, and HVA were observed in depression.
  • R. intestinalis enhanced B. longum abundance, leading to HVA generation.
  • Administration of HVA, B. longum, or R. intestinalis ameliorated depressive symptoms in mice.
  • HVA protected hippocampal neurons by inhibiting synaptic autophagic death.

Conclusions:

  • Gut microbial metabolism, specifically the synergistic interaction between R. intestinalis and B. longum, regulates intestinal neurotransmitter production (HVA).
  • HVA modulates synaptic integrity by preventing autophagic death of hippocampal neurons.
  • Targeting gut microbiota and HVA represents a potential therapeutic strategy for depression.