Ecdysone-mediated intestinal growth contributes to microbiota-driven developmental plasticity under malnutrition

Organ and systemic growth must remain coordinated during development, even under nutritional stress. In Drosophila larvae, the intestinal microbiota contributes to this coordination by promoting growth and maturation under chronic undernutrition. Using gnotobiotic models, we show that association with Lactiplantibacillus plantarum (Lp) selectively enhances midgut growth relatively to other organs, providing an adaptive mechanism that buffers the impact of dietary restriction. Transcriptomic profiling of larval midguts revealed a strong Ecdysone signaling signature upon Lp association. Functional analyses showed that local conversion of Ecdysone to its active form, 20-hydroxyecdysone, by the cytochrome P450 enzyme Shade, together with enterocyte Ecd receptor activity, is required for Lp-dependent intestinal and systemic growth. Pharmacological activation of Ecd signaling partially mimicked the bacterial effect, confirming its sufficiency to drive adaptive midgut expansion. Our results uncover an unexpected role of intestinal Ecd signaling in microbiota-driven developmental plasticity, revealing how commensal bacteria modulate local steroid signaling to fine-tune organismal growth and maturation. Overall design: To uncover transcriptional programs underlying microbiota-dependent intestinal growth, we performed RNA sequencing on midguts dissected from size-matched GF and Lp-associated larvae at early and late third-instar (L3) stages