Summary
This narrative review examines the role of short-chain fatty acids (SCFAs)—primary metabolites of the gut microbiota—in depression pathophysiology. The authors synthesise evidence for how acetate, propionate and butyrate modulate the microbiota-gut-brain axis through neural, endocrine and immune pathways, with specific focus on chronic cerebral hypoperfusion, neuroinflammation, epigenetic modifications and neuroendocrine dysfunction. The review concludes by considering the clinical potential of microbiota-targeted interventions for depressive disorders.
Regional applicability
The mechanistic insights are internationally relevant to UK clinical and research contexts, where depression is a major public health burden. Implementation of microbiota-based therapeutics would require UK-specific dietary and probiotic guidance adapted to local food systems and healthcare infrastructure.
Key measures
Mechanistic pathways of SCFA action in depression; effects on cerebral perfusion, inflammatory markers, epigenetic regulation, and neuroendocrine function
Outcomes reported
The review synthesised the roles of major short-chain fatty acids (acetate, propionate and butyrate) in depression pathophysiology across multiple biological mechanisms. It examined how SCFAs affect chronic cerebral hypoperfusion, neuroinflammation, host epigenome and neuroendocrine alterations within the microbiota-gut-brain axis.
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