Gegen Qinlian decoction alleviates bacterial diarrhea via Lactobacillus amylovorus-modulated restoration of colonic water transport through the cAMP/CFTR/AQP3 pathway.

Bacterial diarrhea involves colonic water absorption dysfunction and gut microbiota disruption. Gegen Qinlian decoction (GQD) is clinically used to treat infectious diarrhea, yet its mechanisms remain incompletely understood. This study aimed to investigate how GQD modulates gut microbiota and enhances colonic water absorption in E. coli-induced diarrhea. Using an E. coli-induced piglet diarrhea model together with a rat colonic perfusion model, results show that GQD alleviates diarrhea-associated intestinal injury and inflammation and improves colonic water absorption. Mechanistically, GQD was associated with increased colonic aquaporin-3 (AQP3) expression and attenuation of the cAMP-protein kinase A-cystic fibrosis transmembrane conductance regulator (cAMP-PKA-CFTR) secretory signaling axis. 16S rRNA sequencing indicated enrichment of Lactobacillus amylovorus after GQD treatment, and administration of L. amylovorus partially reproduced the anti-diarrheal phenotype and transport-related signaling changes. In vitro assays further suggested that GQD suppresses E. coli growth while promoting L. amylovorus metabolic activity, and molecular docking provided hypothesis-generating predictions of candidate phytochemicals and bacterial targets. Overall, GQD may improve bacterial dysbiosis by enriching L. amylovorus and inhibiting E. coli, thereby restoring colonic water transport via the cAMP/CFTR/AQP3 pathway and ultimately improving bacterial diarrhea.