Publication Date
3-26-2024
Journal
Cell Reports
DOI
10.1016/j.celrep.2024.113861
PMID
38416643
PMCID
PMC11037929
PubMedCentral® Posted Date
4-23-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Infant, Child, Animals, Humans, Nutrigenomics, Drosophila, Diet, Metabolic Diseases, Amino Acid Metabolism, Inborn Errors
Abstract
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.
Graphical Abstract
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