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A bacterial route for folic acid supplementation

Maynard, Claire; Cummins, Ian; Green, Jacalyn; Weinkove, David

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Claire Maynard

Ian Cummins

Jacalyn Green


Background: To prevent folate deficiencies, many countries supplement various foodstuffs with folic acid. This compound is a synthetic oxidised folate that differs from naturally occurring reduced folates in its metabolism and uptake. Notably, safety reviews of folic acid supplementation have not considered interactions with gut bacteria. Here, we use the Caenorhabditis elegans – Escherichia coli animal– microbe model to examine a possible bacterial route for folic acid uptake. It has been assumed that supplements are taken up directly by the worm, especially because E. coli is unable to take up folates. However, E. coli, like many other bacteria, can transport the folate breakdown product, para-aminobenzoate-glutamate (PABA-glu), via AbgT and use it for bacterial folate synthesis. This pathway may impact host health because inhibition of bacterial folate synthesis increases C. elegans lifespan. Results: Folic acid supplementation was found to rescue a C. elegans developmental folate-deficient mutant; however, a much higher concentration was required compared to folinic acid, a reduced folate. Unlike folinic acid, the effectiveness of folic acid supplementation was dependent on the E. coli gene, abgT, suggesting a bacterial route with PABA-glu uptake by E. coli as a first step. Surprisingly, we found up to 4% PABA-glu in folic acid preparations, including in a commercial supplement. Via breakdown to PABA-glu, folic acid increases E. coli folate synthesis. This pathway restores folate synthesis in a bacterial mutant defective in PABA synthesis, reversing the ability of this mutant to increase C. elegans lifespan. Conclusions: Folic acid supplementation in C. elegans occurs chiefly indirectly via bacterial uptake of breakdown products via E. coli AbgT, and can impact C. elegans development and longevity. Examining how folic acid supplementation affects bacterial folate synthesis in the human gut may help us to better understand the safety of folic acid supplementation.


Maynard, C., Cummins, I., Green, J., & Weinkove, D. (2018). A bacterial route for folic acid supplementation. BMC Biology, 16, Article 67.

Journal Article Type Article
Acceptance Date Apr 22, 2018
Online Publication Date Jun 15, 2018
Publication Date Jun 15, 2018
Deposit Date Apr 16, 2018
Publicly Available Date Jun 15, 2018
Journal BMC Biology
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 16
Article Number 67


Published Journal Article (1.4 Mb)

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Copyright Statement
© Weinkove et al. 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0<br /> International License (, which permits unrestricted use, distribution, and<br /> reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to<br /> the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver<br /> ( applies to the data made available in this article, unless otherwise stated.

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