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

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.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.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.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.