Brain, behavior, and immunityAug 31, 2026

Short-chain fatty acids and their potential role in reducing depression by affecting the gut-brain connection

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 1, 2026

Abstract

Short-chain fatty acids (SCFAs) may play a role in the relationship between gut microbiota alterations and depressive symptoms.

Dysregulation of the microbiota-gut-brain axis is associated with depression.
Immune and inflammatory signaling may connect changes in gut microbes to depressive symptoms.
SCFAs like acetate, propionate, and butyrate are potential mediators of inflammation and neuroplasticity.
Clinical trials regarding the therapeutic role of SCFAs have produced inconsistent results.
This research aims to evaluate the link between SCFA levels and the severity of depressive symptoms.

Simplified

Dysregulation of microbiota-gut-brain axis has been implicated in depression, with immune and inflammatory signalling representing potential pathways linking gut microbial alterations to depressive symptoms. Short-chain fatty acids (SCFAs), namely acetate, propionate and butyrate are promising immunomodulating mediators of systemic inflammation and neuroplasticity. However, clinical trials of this pathway have given inconsistent results. The aim of this research was to conduct a synthesis of evidence for the therapeutic role of SCFAs using two approaches, to assess association between SCFA levels and depressive symptom severity, and to assess the efficacy of interventions targeting SCFA-related pathways for depressive symptoms.

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Short-chain fatty acids and their potential role in reducing depression by affecting the gut-brain connection

Abstract

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