Gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.

摘要: Accumulating evidence suggests that chronic stress could perturb the composition of gut microbiota and induce host anxiety- depression-like behaviors. In particular, microorganism-derived products can directly or indirectly signal to nervous system. This study sought investigate whether high levels Lactobacillus lactate in rats under unpredictable (CUS) were factors leading anxiety behavior. We collected faeces blood samples a sterile laboratory bench microbiome plasma metabolome from adult male age environment matched healthy individuals. sequenced V3 V4 regions 16S rRNA gene samples. UPLC-MS metabolomics used examine Search for potential biomarkers by combining different data types. Finally, we found regulated signaling pathway through relative expression protein mRNA. Both feeding fecal transplantation caused behavioral abnormalities such as psychomotor malaise, impaired learning memory recipient animals. These also showed inhibition adenylate cyclase (AC)-protein kinase A (PKA) lipolysis after activation G protein-coupled receptor 81 (GPR81) liver, well increased tumor necrosis factor α (TNF-α), compared with controls. Furthermore, sphingosine-1-phosphate 2 (S1PR2) hippocampus was reduced control group its negatively correlates symptom severity. Our suggest microbiome-derived promotes anxiety-like behaviors GPR81 receptor-mediated lipid metabolism pathway.