Impact of imidacloprid exposure on gestational hyperglycemia: A multi-omics analysis

Abstract

Imidacloprid (IMI), a commonly utilized neonicotinoid insecticide, has been identified to adversely impact glucose homeostasis. Pregnant women are believed to be more sensitive to toxins than non-pregnant women, and the impact of IMI exposure on gestational hyperglycemia remain unclear. To explore the impact, pregnant mice fed a high-fat diet were exposed to different doses (0.06, 0.6, 6 mg/kg bw/day) of IMI by gavage. Glucose homeostasis-related parameters were measured. The glucose homeostasis influenced by IMI treatment was explored through integrating gut microbiota, metabolomic and transcriptomic analysis. Results showed that IMI-H (6 mg/kg bw/day) exposure notably restricted gestational weight gain and perturbed glucose homeostasis characterized by reduced glucose tolerance and insulin sensitivity, alongside elevated levels of fasting blood glucose and insulin. Multi-omics analysis revealed that IMI-H exposure induced significant changes in the richness and composition of the gut microbiome. The metabolite profiles of serum samples and cecal contents, and transcriptome of liver and ileum were all affected by IMI-H treatment. The altered gut microbiota, metabolites and genes exhibited significant correlations with glucose homeostasis-related parameters. These differential metabolites and genes were implicated in various metabolic pathways including bile secretion, glucagon signaling pathway, lipid metabolism, fatty acid metabolism. Significant correlations were observed between the altered gut microbiota and caecum metabolome as well as liver transcriptome. For example, the abundance of Oscillibacter was strongly correlated with gut microflora-related metabolites (Icosenoic acid, Lysosulfatide, and fluticasone) and liver differential genes (Grin3b, Lifr, and Spta1). Together, IMI exposure resulted in significant changes in microbial composition, along with alterations in certain metabolites and genes associated with metabolic process, which may promote gestational hyperglycemia.