Microbiota-derived short-chain fatty acids may participate in post-stroke depression by regulating host's lipid

Wenxia Jiang1, Jianjun Chen2, Lei Gong1

  • 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No.1 Yixueyuan Road, Chongqing, China.

Abstract

Insights

Post-stroke depression (PSD) involves altered gut microbes, specifically decreased short-chain fatty acids (SCFAs), which may link gut-brain communication and lipid metabolism changes in the brain.

Area of Science:

  • Neuroscience
  • Microbiology
  • Metabolomics

Background:

  • Post-stroke depression (PSD) is a prevalent condition with unclear pathogenesis.
  • The microbiota-gut-brain (MGB) axis is implicated in both stroke and depression.
  • Understanding the MGB axis role in PSD is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To characterize gut microbial composition and function in PSD rats.
  • To analyze gut-brain metabolic signatures, focusing on lipid metabolism in the prefrontal cortex (PFC).
  • To explore the role of disordered gut microbes in PSD pathogenesis via the MGB axis.

Main Methods:

  • 16S rRNA gene sequencing and fecal metabolome analysis to profile the gut microbiome and metabolites.
  • Liquid chromatography-mass spectrometry (LC-MS) to assess lipid metabolites in the rat PFC.
  • Correlation analysis to link gut microbial changes, metabolites, and brain lipid profiles.

Main Results:

  • PSD rats exhibited significant alterations in 10 gut microbial genera (primarily Firmicutes) and decreased levels of 3 short-chain fatty acids (SCFAs).
  • Gut microbial dysbiosis in PSD rats was significantly associated with altered SCFA levels.
  • PSD rats showed significant changes in 57 lipid metabolites within the PFC, correlated with SCFA alterations.

Conclusions:

  • Short-chain fatty acids (SCFAs) may serve as a key mediator in gut-brain communication relevant to PSD.
  • The Firmicutes-SCFAs-lipid metabolism pathway presents a potential mechanism for investigating the MGB axis in PSD pathogenesis.
  • These findings offer novel insights into the biological underpinnings of PSD and potential therapeutic targets.