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Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis

Xiangyan Zhou1,2, Sixing Wang1,3, Xiaohui Wang4

  • 1Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Frontiers in Nutrition
|August 22, 2025
PubMed

Insights

The gut microbiota influences depression through the microbiota-gut-brain axis via mechanisms like SCFA metabolism and immune interactions. Microbiome-targeted therapies show potential for treating depression.

Area of Science:

  • Neuroscience
  • Microbiology
  • Psychiatry

Background:

  • Depression is a major public health concern with significant individual and societal impacts.
  • Current depression treatments have limited efficacy.
  • Emerging evidence highlights the gut microbiota's role in depression via the microbiota-gut-brain (MGB) axis.

Purpose of the Study:

  • To comprehensively review the mechanisms linking gut microbiota to depression through the MGB axis.
  • To synthesize recent research findings in this field.
  • To evaluate the therapeutic potential of microbiome-targeted interventions for depression.

Main Methods:

  • Literature review synthesizing current research on the MGB axis and depression.
  • Analysis of mechanisms including short-chain fatty acid (SCFA) metabolism, vagal nerve communication, HPA axis regulation, and immune-inflammatory pathways.
  • Evaluation of emerging microbiome-targeted therapies.

Main Results:

  • The gut microbiota influences depression through multiple pathways within the MGB axis.
  • Key mechanisms include SCFA production, neural signaling via the vagal nerve, HPA axis modulation, and immune system regulation.
  • Microbiome-based interventions are a promising area for novel depression treatments.

Conclusions:

  • The gut microbiota plays a crucial role in depression pathophysiology via the MGB axis.
  • Understanding these mechanisms is key to developing effective microbiome-targeted therapies.
  • Further research is needed to establish a theoretical framework for novel therapeutic approaches.
Keywords:
MGB axisdepressiongut microbiotametabolismneuroinflammationneurotransmitters

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