Metabolome‐microbiome modulations induced by <scp>ZIF8</scp> @ <scp>ZIF67</scp> supplementation in the midgut of <i>Bombyx mori</i>

Bombyx mori is an economically crucial lepidopteran insect, and its health is closely related to the gut microbiota and metabolic status. Our previous research confirmed that metal-organic frameworks nanocomposite ZIF8@ZIF67 supplementation can significantly enhance silkworm survival rates upon bacterial challenges without adversely affecting its growth or cocoon weight. To elucidate the mechanism, this study integrated non-targeted metabolomics and 16S rRNA sequencing to dissect ZIF8@ZIF67-driven midgut modulations. The results showed that ZIF8@ZIF67 supplementation led to significant metabolic shifts in the midgut of B. mori, with 96 metabolites up-regulated and 54 down-regulated in the negative ion model, and 117 up-regulated and 43 down-regulated in the positive ion model. Key pathways included glutathione metabolism, purine/pyrimidine metabolism, and histidine metabolism, which are involved in antioxidant defence, nucleotide and protein synthesis for growth and immunity regulation. Furthermore, the gut microbiota composition of B. mori was significantly altered after ZIF8@ZIF67 supplementation, with a marked increase in the relative abundance of Mammaliicoccus and Enterococcus. Lastly, the correlation between metabolites and microbiomes was analysed, including Enterococcus and 1-methylhistidine (r = 0.8895, p = 0.0001), Akkermansia and N-acetyl-d-galactosamine (r = 0.8674, p = 0.0003). These findings demonstrated that ZIF8@ZIF67 could optimise silkworm health by orchestrating metabolite-microbe interactions to enhance nutrient assimilation and oxidative stress resilience, while simultaneously activating pathways essential for growth regulation and immune function.