Larval antibiotic exposure causes persistent impacts on honeybees across life stages via metabolic succession.

Gut microbiomes are profoundly important to host health. In apiculture, antibiotics frequently used to exclude bacterial pathogens can be detrimental to the honeybee gut microbiota and host fitness, generally from larvae to adults. However, the mechanisms underlying these persistent effects remain largely unknown. To address this research gap, we examined the effects of oxytetracycline exposure at different stages on honeybee fitness, including survival, body weight, and gene expression related to immunity and development of adult bees to determine the long-lasting impacts. We employed an absolute quantification of 16S rRNA gene sequencing and non-targeted metabolomics to explore whether and how larval antibiotic exposure affects the adult gut microbiota and related metabolism. Antibiotic exposure induced a long-term survival crisis, reduced weight, and downregulated the expression levels of immune and developmental genes in adult honeybees. Importantly, larval antibiotic exposure significantly influenced the colonization and developmental trajectories of the adult bee gut microbiota, underscoring the potential role of persistent metabolic perturbations in shaping microbial communities. These findings stress the health risks of antibiotic treatment in the larval or adult stages of honeybees and provide valuable metabolic insights into how larval antibiotic exposure influences the gut microbiota of adult bees.