Ganhai Weikang Capsules ameliorate functional dyspepsia in rats by modulating gut microbiota and host metabolic homeostasis

Background Functional dyspepsia (FD) is a prevalent gastrointestinal disorder with limited long-term efficacy of conventional treatments. Ganhai Weikang Capsules (GHWKCs), a classic traditional Chinese medicine formula, has shown remarkable clinical efficacy in alleviating FD symptoms, but its underlying mechanisms, particularly on the gut microbiota-host metabolism axis, remain unclear. Methods We performed chemical profiling of GHWKCs using UPLC-LTQ-Orbitrap-MS and established an FD rat model mimicking the TCM pathogenesis of “spleen deficiency and qi stagnation”. We evaluated gastrointestinal motility, histopathology, serum gastrointestinal hormones, and tissue inflammatory factors. Integrated duodenal metabolomics, cecal 16S rRNA sequencing, and network pharmacology were applied to explore the regulatory mechanisms, with Spearman correlation analysis conducted between differential metabolites and gut microbiota. Results A total of 63 chemical metabolites were identified in GHWKCs. GHWKCs significantly improved gastric emptying and intestinal propulsion, normalized gastrointestinal hormone levels, and inhibited pro-inflammatory cytokine secretion in FD rats. Metabolomics revealed 18 differential metabolites mainly involved in fatty acid β-oxidation and primary bile acid biosynthesis. Gut microbiota analysis showed GHWKCs counteracted dysbiosis, particularly increasing Coriobacteriales and Actinobacteriota abundance. Correlation analysis confirmed a positive correlation between Coriobacteriales and glycocholic acid. Network pharmacology identified 31 active metabolites, 213 intersection targets, and key pathways including PI3K-Akt, MAPK, and Toll-like receptor signaling. Conclusion GHWKCs ameliorate FD through multi-target mechanisms involving improved motility, reduced inflammation, and restored microbiota-metabolic homeostasis. The Coriobacteriales-glycocholic acid axis represents a putative core regulatory pathway bridging TCM theory and modern molecular mechanisms, providing a preclinical mechanistic framework for TCM-based therapy of FD.