Integrated Analysis of Midgut Transcriptome and Microbiome Reveals That Manganese‐Induced Dysbiosis Drives Metabolic Disruption and Developmental Toxicity in Bombyx mori

Manganese (Mn) contamination poses a significant environmental threat, yet the mechanisms underlying its toxicity remain poorly characterised. Here, we used an integrative multi-omics approach to elucidate how dietary Mn disrupts the gut-microbiome axis in the silkworm, Bombyx mori. High-dose Mn exposure triggered severe, dose-dependent growth retardation, reducing larval weight by 55.1%. This was concurrent with profound gut microbiome dysbiosis, evidenced by reduced bacterial diversity, community homogenisation and a sharp decline in beneficial genera such as Delftia, alongside the complete elimination of key commensals like Bifidobacterium. Host midgut transcriptomics revealed 1255 differentially expressed genes, with significant upregulation of detoxification and stress pathways and marked suppression of genes involved in nutrient metabolism. Critically, integrative analysis demonstrated a strong correlation between microbiome disruption and host metabolic gene expression, suggesting that Mn toxicity operates by disrupting the gut microbiome-host metabolic axis. Our findings provide crucial mechanistic insights into heavy metal ecotoxicology and highlight the vulnerability of beneficial insect-microbe symbioses to environmental contamination, with important implications for sustainable agriculture in metal-polluted regions.