[Mechanism of Quzhou Aurantii Fructus in treating rats with functional dyspepsia based on gut microbiota and metabolomics].

The therapeutic effects of Quzhou Aurantii Fructus aqueous extract(QAFA) and Aurantii Fructus aqueous extract(AFA) on functional dyspepsia(FD) in rats were evaluated and compared, and their underlying mechanisms were investigated. The FD rat models were constructed by a combined method of ″pinching tail + irregular diet + drinking dilute acidic water″. The rats were orally administered QAFA at a dose of 2.05 g·kg~(-1)(equivalent to 4 g·kg~(-1) QAF) and AFA at a dose of 1.93 g·kg~(-1)(equivalent to 4 g·kg~(-1) AF), respectively. After 14-day administration, the gastric emptying and intestinal propulsion were assessed. The pathological changes in the gastric antrum and duodenum were analyzed via histology, and the levels of serum gastrin(GAS) and vasoactive intestinal polypeptide(VIP) were measured by enzyme-linked immunosorbent assay. The underlying mechanisms were investigated by using 16S rRNA sequencing and serum metabolomics. The results showed that QAFA and AFA could increase gastrointestinal motility. Hematoxylin-eosin(HE) staining and immunofluorescence analysis showed that both QAFA and AFA repaired the damaged intestinal barrier, and ELISA analysis showed that they regulated GAS and VIP levels in serum. These results suggest that both can improve symptoms in FD rats. The intestinal microbiota analysis revealed that QAFA and AFA reduced the abundance of the harmful microbe Ruminococcus. AFA increased the abundance of the beneficial bacteria Prevotella and Lactobacillus, and QAFA increased the abundance of Clostridia UCG-014. Metabolomic analysis showed that both QAFA and AFA restored serum metabolites primarily through regulating phospholipid metabolism. Correlation analysis between metabolites and gut microbiota showed that both QAFA and AFA decreased the abundance of Ruminococcus, and AFA increased the abundance of Prevotella, thereby restoring serum metabolite levels. These findings suggest that QAFA and AFA may improve FD symptoms in rats by modulating specific gut microbiota to restore gastrointestinal hormones and phospholipid metabolism. However, there are some differences in the specific microbiotas they regulate.