Capsaicin Inhibits Biofilm and Its Related Functions in Helicobacter pylori

Background: Helicobacter pylori is a globally prevalent gastric pathogen associated with chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Its persistence within the gastric niche is strongly linked to biofilm formation, contributing to immune evasion and antibiotic therapy resistance. Methodology: In the present study, we investigated the antibiofilm potential of capsaicin, a natural phytochemical derived from Capsicum species, against H. pylori using experimental and computational approaches. Results: Capsaicin treatment significantly reduced biofilm biomass (up to 75.66 ± 4.00%), metabolic activity (up to 61.23 ± 6.88%), and cell surface hydrophobicity in a dose-dependent manner. Microscopic analyses revealed disrupted biofilm architecture and diminished extracellular polymeric substance at higher concentrations. Molecular docking analysis revealed that capsaicin interacts with target H. pylori proteins (GTP cyclohydrolase II, α-carbonic anhydrase, and urease) through stable hydrogen bonds and hydrophobic contacts. Molecular dynamics simulations further supported the stability of these complexes and demonstrated reduced structural fluctuations upon ligand binding. Free energy landscape analysis suggested ligand-induced conformational alterations in α-carbonic anhydrase, indicating possible structural effects associated with capsaicin interaction. Conclusions: Overall, the findings provide insight into the antibiofilm activity of capsaicin against H. pylori and highlight its potential as a natural adjunct strategy for combating biofilm-associated persistence and antimicrobial resistance.