Antidepression of Xingpijieyu formula targets gut microbiota derived from depressive disorder.

Objective: This investigation aims to determine the antidepressant role of Xingpijieyu formula (XPJYF) mediated via gut microbiota (GM)-brain axis.

Methods: We collected fecal microbiota from patients with depressive disorder (DD) and cultured microbiota in vitro. Some of microbiota were transplanted into germ-free rats with the intragastric administration of XPJYF grain at the dose of 1.533 g/kg/day. The behaviors were studied by forced swimming test, open field test, sucrose preference test, and body weight. Products of hypothalamus-pituitary-adrenocortical (HPA) axis, neurotransmitter, and serum cytokines were investigated by enzyme linked immunosorbent assay. Glial fibrillary acidic protein (GFAP), a biomarker of astrocyte, was quantified using immunofluorescence. Microbiota culturing in vitro after XPJYF treatment was analyze by 16 s RNA sequencing technology. We used lipopolysaccharide (LPS) to mimic activated rat primary astrocyte in vitro. Brain-derived neurotrophic factor (BDNF), cytokines, and oxidative stress factors were determined by western blotting, and glycometabolism in astrocyte was investigated by 2-deoxy-D-glucose (2-DG) uptake, adenosine triphosphate (ATP), and glucose-1-phosphate (G1P) kits.

Results: Microbiota composition during 8 mg/ml of XPJYF (H12-8) for 12 h showed the more consistency. Lactococcus is enriched in DD-derived microbiota composition, and Biffdobacterium and Lactobacillus in H12-8 group. GLUCOSE1PMETAB-PWY and PWY-7328 of which biofunctions were dominantly encoded by Biffdobacterium were the top two of altered pathways. XPJYF improved behaviors and repressed astrocyte activation in depression rats. XPJYF elevated 2-DG uptake, ATP, glucose-1-phosphate, and brain-derived neurotrophic factor (BDNF), and inhibited cytokines and oxidative stress in LPS-induced astrocyte.

Conclusion: XPJYF treatment targets inflammation, activation, and glycometabolim in astrocyte via gut microbiota modulation, thereby improve animal behaviors, HPA axis dysfunction, and neurotransmitter synthesis in depression rats.