Folic acid preventsC. elegansfolate deficiency indirectly via bacterial uptake of a breakdown product: a route that can also increase bacterial toxicity and ageing

Abstract

AbstractSupplementation with the synthetic oxidised folate, folic acid is used to prevent neural tube defects and other symptoms of folate deficiency. However, several unanswered questions remain over folic acid efficacy, safety and interactions with gut microbes. Prevention of a development defect caused by folate deficiency in the nematode wormCaenorhabditis elegansrequires > 10 fold higher concentrations of folic acid compared to folinic acid, a reduced folate. Here we show that the major route for folic acid to restore normal development is indirect via theEscherichia coliused to feedC. elegans.This route occurs mainly via theE. colitransporter AbgT, which takes up the folic acid breakdown product para-aminobenzoate-glutamate (PABA-glu). We found that folic acid preparations, including a commercial supplement, contain 0.3- 4.0 % of this breakdown product. Previously, we have shown that inhibiting bacterial folate synthesis increasesC. eleganslifespan by removing a life-shortening bacterial activity. Here, we show that folic acid restores bacterial folate synthesis and reverses this lifespan increase. It is still to be determined whether this bacterial route increases host folate levels in humans and if there are situations where increased bacterial folate synthesis has negative health complications.