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Updated: Aug 3, 2025

Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
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.
Background:
Post-stroke depression (PSD) is a common mental disorder of stroke survivors, its pathogenesis remains elusive. Previous studies suggested a role of the microbiota-gut-brain (MGB) axis in stroke and depression. In this study, we characterized microbial composition and function, and gut-brain metabolic signatures, in PSD rats. We aim to explore how disordered gut microbes participate in the pathogenesis of PSD through the MGB axis.
Materials And Methods:
16S rRNA gene sequence and fecal metabolome analysis were performed to identify the gut microbiome and their functional metabolites in PSD rats. Then, the lipid metabolic signatures in the prefrontal cortex (PFC) of PSD were conducted by liquid chromatography mass spectrometry. Finally, the potential pathway between gut and brain in the onset of PSD were explored.
Results:
Compared to control and stroke rats, there were 10 genera (most of them belonged to phylum Firmicutes) significantly changed and 3 short chain fatty acids (SCFAs: butyric acid, acetic acid and pentanoic acid) significantly decreased in PSD rats. Meanwhile, altered gut microbial in PSD rats was significantly associated with these SCFAs. Compared with control and stroke rats, 57 lipid metabolites in the PFC of PSD rats were significantly changed. In addition, the altered SCFAs in PSD rats were also significantly correlated with most of disordered lipid metabolites in PFC.
Conclusions:
Our findings suggest that the SCFAs may be a bridge of gut-brain communication. The Firmicutes-SCFAs-lipid metabolism might be a potential pathway to further investigate the MGB axis and pathogenesis of PSD.
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.

