Abstract
BackgroundThe pathogenesis of post-stroke depression (PSD) remains largely unknown. There is growing evidence indicating that gut microbiota participates in the development of brain diseases through the gut-brain axis. Here, we aim to determine whether and how microbial composition and function altered among control, stroke and PSD rats.Materials and MethodsAfter the PSD rat model was successfully established, gut microbiome combined with fecal metabolome approach were performed to identify potentially PSD-related gut microbes and their functional metabolites. Then, correlations between behavior indices and altered gut microbes, as well as correlations between altered gut microbial operational taxonomic units (OTUs) with differential metabolites in PSD rats were explored. Enrichment analysis was also conducted to uncover the crucial metabolic pathways related to PSD.ResultsAlthough there were some alterations in the microbiome and metabolism of the control and stroke rats, we found that the microbial and metabolic phenotypes of PSD rats were significantly different. The microbial composition of PSD showed a decreased species richness indices, characterized by 22 depleted OTUs mainly belonging to phylum Firmicutes, genus Blautia and Streptococcus. In addition, PSD was associated with disturbances of fecal metabolomics, among them Glutamate, Maleic acid, 5-Methyluridine, Gallocatechin, 1,5-Anhydroglucitol, L-Kynurenine, Daidzein, Cyanoalanine, Acetyl Alanine and 5-Methoxytryptamine were significantly related to disturbed gut microbiome (P ≤ 0.01). Disordered fecal metabolomics in PSD rats mainly assigned to lipid, amino acid, carbohydrate and nucleotide metabolism. The steroid biosynthesis was particularly enriched in PSD.ConclusionsOur findings suggest that gut microbiome may participate in the development of PSD, the mechanism may be related to the regulation of lipid metabolism.
Highlights
Post-stroke depression (PSD) is a common mood disorder, which often indicates a poor prognosis (Kutlubaev and Hackett, 2014) and high mortality (Bartoli et al, 2013)
PSD was associated with disturbances of fecal metabolomics, among them Glutamate, Maleic acid, 5Methyluridine, Gallocatechin, 1,5-Anhydroglucitol, L-Kynurenine, Daidzein, Cyanoalanine, Acetyl Alanine and 5-Methoxytryptamine were significantly related to disturbed gut microbiome (P ≤ 0.01)
Our findings suggest that gut microbiome may participate in the development of PSD, the mechanism may be related to the regulation of lipid metabolism
Summary
Post-stroke depression (PSD) is a common mood disorder, which often indicates a poor prognosis (Kutlubaev and Hackett, 2014) and high mortality (Bartoli et al, 2013). Previous studies found that altered gut microbiome has been implicated in stroke and depression (Zheng et al, 2016; Zhu et al, 2016; Chen et al, 2019; Lee et al, 2020; Zheng et al, 2020). A previous study showed that depressed mice were characterized by disturbances in carbohydrate and amino acid metabolism (Zheng et al, 2016). Another study demonstrated that stroke was related to disturbances in amino acid and lipid metabolism (Yamashiro et al, 2017; Chen et al, 2019). The gut microbiome and microbial metabolism of PSD rats have not been explored. We aim to determine whether and how microbial composition and function altered among control, stroke and PSD rats
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