[Anti-depressant mechanism of Bupleuri Radix in regulating hippocampal FGFR1-5-HT_(1A)R heterodimer formation via intestinal flora-short-chain fatty acids].

Bupleuri Radix significantly increased the abundance of three spore-forming bacterial genera and Bacteroides acidifaciens in human intestinal flora cultured in vitro.

• The three spore-forming bacterial genera increased were Ruminococcus, Dorea, and Blautia (P<0.05).
• B. acidifaciens abundance was increased at P<0.001.
• Differential bacteria were identified by real-time quantitative PCR (qPCR) following 16S rRNA sequencing.
• The effect was assessed using in vitro human intestinal flora culture.

Bupleuri Radix administration and transplantation of B. acidifaciens both increased levels of short-chain fatty acids, including acetic acid and butyric acid, in bacterial metabolites.

• Bupleuri Radix administration increased SCFA levels at P<0.001 or P<0.05.
• Transplantation of B. acidifaciens increased SCFA levels at P<0.01.
• SCFA content was determined by the GC-FID method.
• Fecal SCFA content was also measured by GC-FID in the mouse model.

Treatment with Bupleuri Radix, transplantation of B. acidifaciens, or high doses of SCFAs significantly improved depression-like behaviors in mice.

• A depression-like mouse model was established using the 'triple-one' compound stress method.
• Behavioral changes were assessed following gavage with aqueous extract of Bupleuri Radix, transplantation of B. acidifaciens or spore-forming bacteria, or gavage with SCFAs.
• Transplantation of spore-forming bacteria showed no obvious antidepressant effect.
• Behavioral improvements were observed across all three active treatment conditions.

Treatment with Bupleuri Radix, B. acidifaciens transplantation, or high-dose SCFAs increased hippocampal FGF21 protein expression in depressed mice.

• FGF21 protein expression was detected by Western blot.
• Statistical significance was reported at P<0.05, P<0.01, or P<0.001 depending on treatment group.
• FGF21 is fibroblast growth factor 21, expressed in the hippocampus.
• Spore-forming bacteria transplantation did not show obvious effects on FGF21 expression.

Treatment with Bupleuri Radix, B. acidifaciens transplantation, or high-dose SCFAs promoted FGFR1-5-HT1AR heterodimer formation in the hippocampus.

• Heterodimer formation was examined using the Duolink PLA (proximity ligation assay) method.
• Statistical significance was reported at P<0.05 or P<0.01 depending on treatment group.
• The heterodimer involves fibroblast growth factor receptor 1 (FGFR1) and 5-hydroxytryptamine receptor 1A (5-HT1AR).
• Spore-forming bacteria transplantation showed no obvious effect on heterodimer formation.