Background Fasciola hepatica, a globally distributed helminth, causes fasciolosis, a disease with significant health and economic impacts. Variability in triclabendazole (TCBZ) efficacy and emerging resistance are remaining challenges. Evidence suggests that the gut microbiome influences host-helminth interactions and is associated with anthelmintic effects, but its association with human F. hepatica infection and TCBZ efficacy is not well understood. Methods In this study, we investigated the relationship between Fasciola hepatica infection and the gut microbiome through metagenomic shotgun sequencing of 30 infected and 60 age- and sex-matched uninfected individuals from Peru. Additionally, we performed a longitudinal analysis to evaluate microbiome dynamics in relation to TCBZ treatment response. Results and discussion Infection was associated with specific microbial taxonomic and func...