Fructus Gardeniae alleviates acute pancreatitis via restoring gut microbiota and short-chain fatty acids

Intestinal microbial dysbiosis has emerged as a pivotal contributor to the pathogenesis and progression of acute pancreatitis (AP). Nevertheless, therapeutic strategies that specifically target the gut microbiota to attenuate pancreatic injury remain limited. Here, we investigated whether Fructus Gardeniae (FG), a medicinal herb with known bioactivity, exerts protective effects against caerulein (Cae)-induced AP through reconstitution of the gut microbial ecosystem. Mice were pretreated with FG for seven consecutive days prior to Cae challenge, followed by comprehensive evaluation of pancreatic pathology, intestinal barrier integrity, inflammatory responses, gut microbial composition, and short-chain fatty acids (SCFAs) profiles. FG administration markedly attenuated pancreatic damage, reduced systemic endotoxemia, preserved intestinal tight junction integrity, and suppressed pro-inflammatory cytokine release. 16S ribosomal RNA (16S rRNA) gene sequencing revealed that FG effectively reversed AP-associated microbial dysbiosis by enriching beneficial taxa including Ligilactobacillus and Muribaculaceae, while concurrently suppressing conditionally pathogenic phyla such as Pseudomonadota. Concurrently, FG restored cecal SCFA concentrations, particularly acetate, propionate, and butyrate, and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways linked to butanoate and propanoate metabolism. Critically, fecal microbiota transplantation (FMT) from FG-treated donors into antibiotic-depleted recipients recapitulated the protective phenotype, as evidenced by ameliorated pancreatic and intestinal injury, reduced inflammatory markers, and restoration of recipient microbial diversity toward that of healthy controls. Collectively, these findings demonstrate that FG alleviates AP substantially through microbiota-dependent mechanisms, alongside potential direct effects on host tissues, highlighting FG as a promising natural therapeutic agent for microbiome-targeted intervention in AP.