The physiological and toxicological effects of antibiotics on an interspecies insect model

Silkworm (Bombyx mori L.) has a clear genetic background, parts of which are highly homologous to certain genes related to human hereditary diseases. Thus, the species presents an excellent interspecies model for drug screening and microbe-host interaction studies. Chloramphenicol (CAM) and vancomycin (VCM) are antibiotics commonly used to treat specific bacterial infections in medical care, animal husbandry, and agriculture. However, inappropriate dosages and prolonged therapy increase their risk of toxicity. In this work, we investigated the physiological and toxicological responses of silkworm to combined oral administration of CAM and VCM. Results showed that antibiotics promote the feeding behavior of silkworm and significantly reduce (P < 0.05) intestinal cultivable bacterial counts. Moreover, antibiotics decreased the antioxidant enzyme activities of superoxide dismutase, catalase, glutathione S-transferase, and thioredoxin reductase and caused oxidative damage to the silkworm intestine; the degree of damage was confirmed by histopathology analysis. The gene expression levels of antimicrobial peptides (attacin, lysozyme, and cecropins) were also perturbed by antibiotics. After antibiotic exposure, 16S rRNA metagenomic sequencing revealed increases in the relative abundance of Sphingobium, Burkholderia, Barnesiella, Bacteroides, Bradyrhizobium, Acinetobacter, Phenylobacterium, Plesiomonas, Escherichia/Shigella, and unclassified bacteria, as well as a reduction of Enterococcus. The metabolic and functional profiles of intestinal microbiota, particularly metabolic processes, such as energy, cofactors and vitamins, lipid, amino acid, and carbohydrate metabolisms, changed after antibiotic exposure. In conclusion, our findings reveal that antibiotics exert substantial effects on silkworm. The present study may promote the applications of silkworm as an interspecies model in the medical and pharmaceutical fields.