A flexible synthetic diet platform for Drosophila nutrigenomics

Nutrient-gene interactions are key determinants of metabolic disease phenotypes, but systematic analysis remains constrained by the labour required to generate precisely defined diets. To address this, we developed a flexible method for assembling synthetic diets for Drosophila melanogaster from individual stock solutions, enabling rapid and controlled modification of dietary composition. Using this approach, we generated a rational array of 51 diets in which single nutrients were varied systematically. We first showed that diets prepared using the flexible method performed comparably to standard preparation methods in wild-type flies, with similar developmental timing, survival, adult body weight, and starvation resistance. As a proof-of-concept, we then applied this dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe metabolic disorder caused by defective sulfur amino acid catabolism. This validated previously identified nutrient-specific effects, including survival and pupariation rescue by cysteine depletion, while also revealing additional amino acid-modified diets that improved pupal survival. This platform provides a scalable and versatile in vivo framework for systematically interrogating genotype-specific nutritional responses in Drosophila . It should facilitate the identification of diet-gene interactions relevant to metabolic disease and support broader nutritional screening across disease models.