Integrated Transcriptomic and Physiological Analyses Reveal Disruption of Digestive Homeostasis Induced by Protease Inhibitors in Anticarsia gemmatalis Caterpillars

ABSTRACT Protease inhibitors (PIs) are promising bioactive compounds for sustainable pest management because they interfere with the digestive processes of herbivorous insects. However, the physiological mechanisms underlying insect adaptation to natural and synthetic PIs remain poorly understood. Here, we investigated the midgut responses of Anticarsia gemmatalis Hübner (Lepidoptera: Erebidae) to the soybean Kunitz trypsin inhibitor (SKTI) and the synthetic tripeptide GORE‐2 using integrated transcriptomic, biochemical, and histological approaches, complemented by an exploratory metatranscriptomic analysis of putative gut‐associated microbial transcripts. RNA‐seq analysis identified 2542 unique differentially expressed genes (FDR‐adjusted p  A. gemmatalis larvae. These results underscore the potential of synthetic peptide‐based protease inhibitors to interfere with adaptive digestive processes in pest insects of agricultural importance.