New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by Modulation: Joint Clinical and Animal Data.

Tetratricopeptide repeat and ankyrin repeat containing 1 () is a robust risk gene of bipolar disorder (BD). However, little is known on the role of in the pathogenesis of BD and whether the gut microbiota is capable of regulating expression. In this study, we first investigated the serum mRNA level of in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain expression and neuroinflammation, which was further verified by Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of mRNA was higher in depressed patients than that of healthy controls. Mice harboring 'BD microbiota' following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and were elevated in mice hippocampus and prefrontal cortex. , LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of .