Human activities and horizontal gene transfer shape the resistome landscapes of non-human primates

Antibiotic resistance represents a growing threat to human, animal, and ecosystem health, yet its dynamics in wildlife remain poorly understood. We conducted a systematic analysis of the gut resistomes in non-human primates (NHPs) and environmental soils in Guizhou Province, China, a biodiversity hotspot. Metagenomic analyses reveal that human activities and horizontal gene transfer (HGT) influence primate resistome landscapes and enhance their dissemination potential. A total of 1927 antibiotic resistance ontologies (AROs) distributed across 1477 species-level genome bins (SGBs), providing a comprehensive genomic catalog of the NHPs resistome. Bacterial genera such as Pseudomonas, Stenotrophomonas, and Comamonas drive ARG mobilization, with a core subset of ARGs that reliably predict overall resistance burdens. Notably, widely distributed primate species, with large habitat ranges and frequent interspecies interactions exhibit the most potential for ARG dissemination. Ecological modeling identifies current and future hotspot regions requiring prioritized monitoring amid ongoing human disturbance and climate change. These findings provide a molecular-indicator-based framework for environmental antibiotic resistance (AR) monitoring and conservation strategies for endangered species. Despite limitations in temporal and spatial coverage, our study highlights the need to integrate wildlife, particularly NHPs, as sentinel species into "One Health" AR surveillance and policy. This approach will strengthen our understanding of ARG transmission dynamics and their long-term impacts on host adaptation, ecosystem stability, and public health.