Correlation Between Gut Microbiota and Plasma Metabolites in a Mouse Model for Post-Traumatic Stress Disorder

Background: The gut microbiota and plasma metabolites have been shown to contribute to the etiology of post-traumatic stress disorder (PTSD). The relationship between the gut microbiome and plasma metabolome in PTSD is poorly understood. This study aims to integrate the gut microbiome data and plasma metabolome data to elucidate microbial–metabolite associations specific for PTSD in a mouse model. Methods: A PTSD mouse model was induced by single prolonged stress and electric foot shock (SPS&S). We sequenced the gut microbiota composition by 16S rRNA gene sequencing and used ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) for the plasma metabolomic profiling to explore the association between the gut microbiota and the plasma metabolites in mice with PTSD. Results: The PTSD mice exhibited robust anxiety-like behaviors, significantly elevated plasma IL-1β and TNF-α, and profound gut dysbiosis characterized by a marked depletion of Muribaculaceae and Akkermansia and expansion of the Lachnospiraceae_NK4A136_group. The plasma metabolomics identified 24 significantly dysregulated metabolites, including upregulated L-arginine, palmitic acid, and oleic acid, and downregulated uridine. The pathway enrichment analysis revealed coordinated perturbations in arginine biosynthesis, pyrimidine metabolism, unsaturated fatty acid biosynthesis, and glycerophospholipid metabolism. Critically, genus-level correlation analysis uncovered biologically coherent associations. The Muribaculaceae abundance showed strong negative correlations with L-arginine and palmitic acid and positive correlations with L-glutamine and thymidine. Conclusions: This study provides an exploratory investigation into the association network between the gut microbiota and the plasma metabolites in a PTSD mouse model, offering preliminary insights into potential microbe–metabolite interactions in PTSD.