Anthropogenic Pressure Shapes Gastrointestinal Immunopathology and Antimicrobial Resistance in Wild Boar (Sus scrofa) Across a Human–Wildlife Interface in Iran

The Eurasian wild boar ( Sus scrofa ) occupies a pivotal position at the human–livestock–wildlife interface, yet its role in antimicrobial resistance (AMR) ecology remains poorly characterized in Southwest Asia. This study investigated whether anthropogenic pressure shapes the gastrointestinal ecosystem of wild boar by integrating enteric resistome dynamics with mucosal immunopathology within a One Health framework. Intestinal contents and matched ileal and colonic tissues were collected from 87 wild boars across a defined anthropogenic gradient in Iran, spanning protected forests to peri-urban agricultural landscapes. Shotgun metagenomic sequencing was used to characterize resistome composition, pathogenic lineages, and mobile genetic elements, while quantitative histopathology and immunohistochemistry were applied to assess subclinical mucosal inflammation. Resistome diversity and total antimicrobial resistance gene (ARG) abundance increased significantly with anthropogenic pressure and were strongly associated with histopathological indicators of chronic enteritis, including villus atrophy and lymphoplasmacytic infiltration. High-pressure zones harbored clinically relevant resistance determinants, notably extended-spectrum β-lactamase genes, and pandemic Escherichia coli sequence type ST131 carried on broad-host-range plasmids. Integrated mixed-effects modeling identified anthropogenic pressure as the dominant predictor of ARG burden, with a significant interaction between inflammation severity and resistance load. These findings demonstrate that wild boar function as anthropogenically modulated reservoirs and potential amplifiers of high-risk AMR at the landscape scale. By linking microbial genetic potential to host tissue response, this study provides mechanistic evidence that wildlife gut ecosystems can facilitate resistance persistence and dissemination, with direct implications for public health, livestock biosecurity, and the conservation of sympatric apex predators.