Gut microbiota mediates the antidepressant-like effects of xiaochaihutang: mechanisms involving inhibition of inflammation and enhancement of barrier function.

Depression is a common mental disorder that seriously impairs the psychological and physical health of patients. Extensive research has indicated that patients with depression exhibit disturbances in their gut microbiota. Xiaochaihutang (XCHT) is a traditional herbal recipe widely used in China, and previous studies have found it to possess antidepressant properties. However, whether XCHT can modulate depression-associated gut microbiota dysbiosis remains unclear. In this research, we investigated the impact of XCHT on the microbiota-gut-brain axis in depressed rats and elucidated the potential mechanisms. A rat model of depression was established using the chronic unpredictable mild stress (CUMS) protocol. Behavioral tests demonstrated that XCHT significantly alleviated depression-like behaviors. 16S rRNA sequencing revealed that XCHT enhanced the diversity and compositional structure of the gut microbiota and specifically increased the abundance of the beneficial bacterium Blautia. Fecal microbiota transplantation (FMT) experiments further confirmed that the antidepressant-like effects of XCHT were mediated through modulation of the gut microbiota. Furthermore, XCHT exhibited anti-inflammatory properties in both the central and peripheral systems and improved the integrity of the intestinal barrier and the blood-brain barrier. These mechanisms were also validated using the FMT approach. Collectively, these findings suggest that the antidepressant-like mechanism of XCHT may be directly linked to the regulation of the microbiota-gut-brain axis. This study demonstrates that XCHT exerts antidepressant-like effects by modulating the microbiota-gut-brain axis, providing novel insights into the potential therapeutic mechanisms and clinical applications for depression.