Species-associated toxicological trajectories in social bees exposed to sublethal metribuzin: A multi-omics perspective on host-microbiome interactions.

The divergent sensitivities of honeybees (Apis mellifera) and bumblebees (Bombus terrestris) to agrochemicals challenge the one-species-fits-all framework of ecological risk assessment, yet the mechanistic basis for this variation remains underexplored. Here, we used an integrated multi-omic approach, combining transcriptomics, metabolomics, and gut metagenomics, to map the species-associated responses of these pollinators under sublethal metribuzin (MET) exposure (30 mg/kg). Honeybees, exhibited broad transcriptional activation accompanied by suppressed P450 and glutathione S-transferase (GST) activities, metabolically associated with a disruption in cellular cofactor (NADPH/FAD) biosynthesis pathways, coincided with midgut tissue pathology and microbial structural dysbiosis. Conversely, bumblebees showed targeted cytochrome P450 (CYP) induction and elevated P450/GST activities, linked to an energy-intensive rewiring of carbohydrate metabolism that supported both xenobiotic clearance and antioxidant defense. While the bumblebee gut microbiota remained structurally stable, it displayed functional shifts toward xenobiotic efflux and cellular cytoprotection. Collectively, our multi-omic landscapes delineate two divergent correlative models: metabolic impairment coupled with microbial dysbiosis in honeybees, versus physiological resilience associated with microbiome functional plasticity in bumblebees. These findings propose a testable framework wherein baseline metabolic capacity shapes species-associated trajectories of host-microbiome interactions under herbicide stress, highlighting the critical need to incorporate mechanistic insights from multi-species comparisons into future ecological risk assessments.