Azadirachtin directly or indirectly affects the abundance of intestinal flora of Spodoptera litura and the energy conversion of intestinal contents mediates the energy balance of intestine-brain axis, and along with decreased expression CREB in the brain neurons

Azadirachtin is a good growth inhibitor for Lepidopteran larvae, but its effect on the brain neurons, intestinal flora and intestinal contents caused by the growth inhibition mechanism has not been reported yet. This study explored the mechanism of azadirachtin on the growth and development of Spodoptera litura larvae and brain neurons through three aspects: intestinal pathology observation, intestinal flora sequencing, and intestinal content analysis. The results showed that the treatment of azadirachtin led to the pathological changes in the structure of the midgut and the goblet cells in the intestinal wall cells to undergo apoptosis. Changes in the host environment of the intestinal flora lead to changes in the abundance value of the intestinal flora, showing an increase in the abundance value of harmful bacteria such as Sphingomonas and Enterococcus, as well as an increase in the abundance value of excellent flora such as Lactobacillus and Bifidobacterium. Changes in the abundance of intestinal flora will result in changes in intestinal contents and metabolites. The test results show that after azadirachtin treatment, the alkane compounds in the intestinal contents of the larvae are greatly reduced, and the number of the long carbon chain and multi-branched hydrocarbon compounds is increased, unsaturated fatty acids, silicon‑oxygen compounds and ethers. The production of similar substances indicates that azadirachtin has an inhibitory effect on digestive enzymes in the intestines, which results in the inhibition of substance absorption and energy transmission, and ultimately the inhibition of larval growth and brain neurons. [Display omitted] •Intake of azadirachtin leads to damage of intestinal structure in the larvae of Spodoptera litura.•Azadirachtin leads to the change of abundance of intestinal flora.•Azadirachtin affects metabolism and energy absorption.•Azadirachtin directly or indirectly causes brain neuronal development inhibition.