Background  Antimicrobial resistance is a major global health concern, with the environment playing a key role in its emergence and spread. Understanding the relationships between environmental factors, microbial communities, and resistance mechanisms is vital for elucidating environmental resistome dynamics. In this study, we characterized the environmental resistome of the Baltic Sea and evaluated how environmental gradients and spatial variability, alongside its microbial communities and associated functional genes, influence resistome diversity and composition across geographic regions.

Results  We analyzed the metagenomes of benthic sediments from 59 monitoring stations across a 1,150 km distance of the Baltic Sea, revealing an environmental resistome comprised of predicted antimicrobial resistance genes (ARGs) associated with resistance against 26 antibiotic classes. We observed spatial variation in its resistance profile, with higher resistome diversity in the northern regions and a decline in the dead zones and the southern areas. The combined effects of salinity and temperature gradients, alongside nutrient availability, created a complex environmental landscape that shaped the diversity and distribution of the predicted ARGs. Salinity predominantly influenced microbial communities and predicted ARG composition, leading to clear distinctions between high-saline regions and those with lower to mid-level salinity. Furthermore, our analysis suggests that microbial community composition and mobile genetic elements might be crucial in shaping ARG diversity and composition.

Conclusions  We presented that salinity and temperature were identified as the primary environmental factors influencing resistome diversity and distribution across geographic regions, with nutrient availability further shaping these patterns in the Baltic Sea. Our study also highlighted the interplay between microbial communities, resistance, and associated functional genes in the benthic ecosystem, underscoring the potential role of microbial and mobile genetic element composition in ARG distribution. Understanding how environmental factors and microbial communities modulate environmental resistomes will help predict the impact of future environmental changes on resistance mechanisms in complex aquatic ecosystems.