A flexible diet platform for the nutrigenomic screening of Drosophila disease models

Abstract

Nutrient-gene interactions shape metabolic disease phenotypes, but systematic testing is limited by the effort required to produce defined diets. We developed a flexible protocol that assembles precisely defined synthetic diets for Drosophila melanogaster from individual stock solutions. Using this approach, we generated a rational array of 51 single-nutrient-varied diets and demonstrated that flexible and standard preparation methods produce comparable developmental timing, survival, adult body weight, and starvation resistance in wildtype flies. Applying the dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe condition caused by impaired sulfur amino acid catabolism, revealed nutrient-specific effects on pupal survival and pupariation timing, including rescue by cysteine depletion and other amino acid modified diets. This platform provides a scalable in vivo framework for mapping genotype-specific nutritional responses across Drosophila disease models. Key pointsO_LIDeveloped a flexible platform for assembling precisely defined synthetic diets in Drosophila. C_LIO_LIGenerated a rational 51-diet array, enabling scalable nutrigenomic screening. C_LIO_LIFlexible and standard diet preparations yielded matching developmental and adult fitness outcomes. C_LIO_LIDietary array screening in a sulfite oxidase deficiency model recapitulated cysteine sensitivity and identified novel nutrient modifiers. C_LI