Mechanistic insights and synergistic effects of Qi-Fu-Qing-You formulation in combating Helicobacter pylori infection and maintaining gut microbial homeostasis

Helicobacter pylori (H. pylori) infection affects over half of the global population, leading to chronic gastritis, gastric ulcers and cancer. Traditional antibiotic therapies face challenges such as resistance and gut microbiota dysbiosis, necessitating alternative solutions. Qi-Fu-Qing-You (QFQY) formulation was developed using medicinal and edible plants. This study investigated its anti- H. pylori efficacy, active components, and mechanisms of action. Phytochemical analysis revealed bioactive compounds such as ellagic acid, gallic acid, and psoralen, which demonstrated significant antibacterial activity against both antibiotic-sensitive and -resistant H. pylori strains. Molecular dynamics simulations showed that these compounds bind to the allosteric site of penicillin-binding protein 1 A (PBP1A), enhancing antibiotic binding affinity and improving antibacterial efficacy. In vivo studies confirmed QFQY's ability to mitigate antibiotic-induced intestinal damage through anti-inflammatory and anti-apoptotic effects, maintaining gut microbiota balance. The results underscore QFQY's potential as a functional food for H. pylori management and as an adjunct to antibiotic therapies. Highlights • A UPLC-ESI-MS/MS method systematically identified chemical constituents in QFQY formulation. • Pivotal active compounds (psoralen, ellagic acid, gallic acid) were identified in anti- H. pylori . • QFQY enhances the antibiotic binding affinity of PBP1A and alleviates drug resistance in H. pylori. • QFQY alleviates antibiotic-induced intestinal damage and prevents gut microbiota dysbiosis.