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Dual Metabolic Compensation to Dietary Choline Deficiency by the Drosophila Hologenome

Fujita, Y.; Morozumi, S.; Kosakamoto, H.; Arita, M.; Obata, F.

2025-12-13 physiology
10.64898/2025.12.11.693343 bioRxiv
Show abstract

Coping with an unbalanced diet is critical in animals. However, the mechanisms that mitigate deficiencies of specific nutrients, such as choline, remain poorly understood. Choline is converted to phosphatidylcholine (PC), a major phospholipid. Using genetic, nutritional, and microbiome manipulation tools in Drosophila melanogaster, we identified two independent mechanisms that ameliorate the effects of choline deficiency. First, a strain of commensal bacteria synthesizes PC via choline-independent pathway and provides it to the host. Second, a host-derived phospholipid, {beta}-methylphosphatidylcholine ({beta}mPC), is generated from carnitine, which compensates choline deficiency as a functional analog of PC. Our findings reveal microbial and host metabolic processes that modulate dietary requirement for choline. This study also provides evidence that hologenomic coordination of metabolism enables animals to adapt to a micronutrient deficiency.

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