A bacterial route for folic acid supplementation.
A bacterial route for folic acid supplementation.
复制标题
DOI：
10.1186/s12915-018-0534-3
复制
发表时间：
2018-06-15
期刊：
影响因子：
5.4
通讯作者：
Weinkove D
中科院分区：
文献类型：
--
作者：
Maynard C;Cummins I;Green J;Weinkove D
为了防止叶酸缺乏，许多国家在各种食品中添加叶酸。这种化合物是一种合成的氧化叶酸，在代谢和吸收方面不同于自然发生的还原叶酸。值得注意的是，叶酸补充剂的安全性评估没有考虑到与肠道细菌的相互作用。在这里，我们使用秀丽隐杆线虫-大肠杆菌动物-微生物模型来检查叶酸摄取的可能细菌途径。人们一直认为补充剂是由蠕虫直接吸收的，特别是因为大肠杆菌无法吸收叶酸。然而，像许多其他细菌一样，大肠杆菌可以通过AbgT运输叶酸分解产物对氨基苯甲酸-谷氨酸（PABA-glu），并将其用于细菌叶酸合成。这一途径可能影响宿主健康，因为抑制细菌叶酸合成可延长秀丽隐杆线虫的寿命。补充叶酸可以挽救秀丽隐杆线虫发育中的叶酸缺乏突变体；然而，与叶酸相比，所需的浓度要高得多，叶酸是一种还原的叶酸。与叶酸不同，叶酸补充的有效性取决于大肠杆菌基因abgT，这表明大肠杆菌首先摄取PABA-glu是一条细菌途径。令人惊讶的是，我们在叶酸制剂中发现了高达4%的PABA-glu，包括在商业补充剂中。通过分解成PABA-glu，叶酸增加了大肠杆菌叶酸的合成。该途径在PABA合成缺陷的细菌突变体中恢复叶酸合成，逆转了该突变体增加秀丽隐杆线虫寿命的能力。秀丽隐杆线虫的叶酸补充主要通过细菌通过大肠杆菌AbgT摄取分解产物间接发生，并且可以影响秀丽隐杆线虫的发育和寿命。研究叶酸补充剂如何影响人体肠道中细菌叶酸合成可能有助于我们更好地了解叶酸补充剂的安全性。本文的在线版本（10.1186/s12915-018-0534-3）包含补充材料，授权用户可使用。
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. 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. 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. The online version of this article (10.1186/s12915-018-0534-3) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
3.2
作者：
Carter, Eric L.;Jager, Lindsey;Green, Jacalyn M.
通讯作者：
Green, Jacalyn M.
DOI：
10.3945/ajcn.113.080507
发表时间：
2014-08
期刊：
The American journal of clinical nutrition
影响因子：
--
作者：
Patanwala I;King MJ;Barrett DA;Rose J;Jackson R;Hudson M;Philo M;Dainty JR;Wright AJ;Finglas PM;Jones DE
通讯作者：
Jones DE
影响因子：
11.8
作者：
Chaudhari SN;Mukherjee M;Vagasi AS;Bi G;Rahman MM;Nguyen CQ;Paul L;Selhub J;Kipreos ET
通讯作者：
Kipreos ET
DOI：
10.1016/j.jasms.2007.01.017
发表时间：
2007-05-01
影响因子：
3.2
作者：
Lu, Wenyun;Kwon, Yun Kyung;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
DOI：
10.1007/978-1-61779-197-0_10
发表时间：
2011-01-01
期刊：
STRAIN ENGINEERING: METHODS AND PROTOCOLS
影响因子：
--
作者：
Moore, Sean D.
通讯作者：
Moore, Sean D.