| Sumario: | Terminalia bellirica (Gaertn.) Roxb. (Combretaceae) (T. bellirica) is a longstanding medicinal plant traditionally referenced in both Indian and Tibetan medical practices. Currently, approximately 50% of the global population is infected with Helicobacter pylori (H. pylori). To curb antibiotic overuse, asymptomatic patients might require alternative therapy to mitigate the intestinal side effects commonly associated with excessive antibiotic usage. Preliminary screening conducted by our team revealed that T. bellirica had excellent anti- H. pylori action in vitro. However, further research elucidating the mechanism behind T. bellirica 's impact on H. pylori infection and its protective effects against related gastrointestinal diseases is yet to be explored. To assess the specific effect and underlying mechanism, we employed a comprehensive range of methodologies, including UPLC-MS/MS, in vitro and in vivo antibacterial assays, 5R 16S, molecular dynamics simulation and RT-qPCR. Phytochemical analysis revealed abundant phenolic contents in T. bellirica , including chebulagic acid, chebulinic acid, corilagin, gallic acid, and ellagic acid. In vitro antibacterial evaluations demonstrated significant efficacy of T. bellirica against H. pylori , with a minimum inhibitory concentration (MIC) of 160 μg/mL, effectively inhibiting critical bacterial defense such as urease, adhesion and gene vacA. In vivo animal experiments showed that in addition to its anti- H. pylori effect, T. bellirica exhibited mild influence on gastric microbiota, with the composition restoring to normal levels after administration. T. bellirica exerts potent anti- H. pylori activity both in vitro and in vivo , indicating its potential as an alternative therapeutic strategy for managing H. pylori infections while exerting minimal impact on gastric microbial balance. Further studies are warranted to elucidate additional pathways involved and to validate its clinical applications. [Display omitted] • Terminalia bellirica demonstrated potent anti- Helicobacter pylori efficacy in vitro and in vivo. • Treatment with T. bellirica minimized disruption of the gastric microbiota during H. pylori infection. • Mechanistic studies showed T. bellirica inhibited H. pylori infection by suppressing urease activity and bacterial adhesion.
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