Protoxin-derived L-serine drives pathogenicity of gut bacteria <i>Enterococcus</i> through biofilm induction

Environmental stressors can disrupt the delicate balance between host and gut microbiota, yet the molecular signals that drive pathogenicity of midgut bacteria remain poorly understood. Here, we report that proteolytic digestion of the Bacillus thuringiensis insecticidal protoxin in the insect gut releases free L-serine. This amino acid acts not as a nutritive source but as a critical metabolic cue that reprograms a newly discovered species of gut bacteria, Enterococcus. Through integrated metabolomic, transcriptomic, and phenotypic analyses, we demonstrate that L-serine induces a state of enhanced stress resistance that triggered robust biofilm formation in Enterococcus by upregulating pathways including the phosphotransferase system and LPXTG-motif adhesion proteins. This enables opportunistic pathogenic Enterococcus to thrive in the dysbiotic gut environment, translocate systemically, and ultimately accelerate host mortality. Our findings reveal a new mechanism by which exotic protoxin-derived metabolic signals can directly modulate gut microbial behavior, converting a commensal into a pathobiont. This paradigm extends our understanding of microbiome-mediated disease etiology, suggesting that similar metabolite-mediated functional shifts may underpin dysbiotic states in diverse host ecosystems triggered by dietary or immune protein degradation.