Summary The symbiotic association between bacterial symbionts and insect hosts is a complicated process that is not completely understood. Herein, we used a silkworm model to study the association between symbiotic Bacillus and lepidopteran insect by investigating the changes in intestinal microbiota and hemolymph circulating metabolites of silkworm after symbiotic Bacillus subtilis treatment. Results showed that B. subtilis can generate a variety of primary and secondary metabolites, such as B vitamins and antimicrobial compounds, to provide micronutrients and enhance the pathogen resistance of their insect host. Shifts in the relative abundance of Enterococcus, Brevibacterium, Buttiauxella, Pseudomonas, Brevundimonas and Limnobacter had significant correlations with the concentrations of differential metabolites (e.g. phospholipids and certain amino acids) in insect hemolymph. The antimicrobial compounds secreted by B. subtilis were the primary driving force for the reconstruction of intestinal microbiota. Meanwhile, the altered levels of circulating metabolites in multiple metabolic pathways were potential adaptive mechanism of insect hosts in response to the shifts of intestinal microbiota. Our findings provided concrete evidence that bacterial intestinal symbiont can alter the physiological state of insects and highlighted the importance of the compositional alterations of intestinal microbiota as a source of variation in circulating metabolites of insect hosts.
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