The Microbiota‐Gut‐Brain Axis in the Pathophysiology of Major Depressive Disorder: A Mechanistic Review

Jan 14, 2026Comprehensive Physiology

How Gut Bacteria and Brain Communication May Relate to Major Depression

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Abstract

Disruptions within the microbiota-gut-brain axis may contribute to the development and maintenance of Major Depressive Disorder (MDD).

  • Gut dysbiosis and compromised intestinal barrier integrity are foundational states observed in patients with MDD.
  • Microbial metabolites, such as short-chain fatty acids and tryptophan products, act as important signaling molecules in the MGB axis.
  • These signals are transmitted to the central nervous system through direct neural pathways and systemic processes.
  • Gut-derived inflammation and microglial activation may play roles in the pathophysiology of MDD.
  • Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with the clinical manifestations of MDD.

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