Martelli, F., Lin, J., Mele, S., Imlach, W., Kanca, O., Barlow, C.K., Paril, J., Schittenhelm, R.B., Christodoulou, J., Bellen, H.J., Piper, M.D.W., Johnson, T.K. (2024). Identifying potential dietary treatments for inherited metabolic disorders using Drosophila nutrigenomics.  Cell Rep. 43(3): 113861.

FBrf0259145

Research paper

Inherited metabolic disorders are a group of genetic conditions that can cause severe neurological impairment and child mortality. Uniquely, these disorders respond to dietary treatment; however, this option remains largely unexplored because of low disorder prevalence and the lack of a suitable paradigm for testing diets. Here, we screened 35 Drosophila amino acid disorder models for disease-diet interactions and found 26 with diet-altered development and/or survival. Using a targeted multi-nutrient array, we examine the interaction in a model of isolated sulfite oxidase deficiency, an infant-lethal disorder. We show that dietary cysteine depletion normalizes their metabolic profile and rescues development, neurophysiology, behavior, and lifelong fly survival, thus providing a basis for further study into the pathogenic mechanisms involved in this disorder. Our work highlights the diet-sensitive nature of metabolic disorders and establishes Drosophila as a valuable tool for nutrigenomic studies for informing potential dietary therapies.

PMC11037929 (PMC) (EuropePMC)