论文题目：A bacterial route for folic acid supplementation

期刊：BMC Biology

作者：Claire Maynard et al.

发表时间：2018/6/15

数字识别码：10.1186/s12915-018-0534-3

原文链接：https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0534-3?utm_source=Other_website&utm_medium=Website_links&utm_content=DaiDen-BMC-BMC_Biology-Biology-China&utm_campaign=BMCF_USG_BSCN_DD_BMCBiology_folicacid

补充的叶酸如何进入我们的身体？其吸收方式曾被认为与饮食中的天然叶酸相同，但是实际上却是通过人体内不同的蛋白质通道吸收。在近期的论文中，我们发现了另一条途径，即通过肠道细菌吸收，并讨论这可能对人类健康产生的影响。

我们的工作在线虫中展开，它们以无害的大肠杆菌菌落为食物，能够在实验室中进行培养。对叶酸的兴趣来自一个偶然发现：抑制大肠杆菌中叶酸的产生能够延长蠕虫的寿命。有趣的是，寿命的延长并不是叶酸供应减少的结果。相反，阻止细菌叶酸产生以一种对线虫有益的方式改变了细菌的行为或新陈代谢。

线虫可以从大肠杆菌中获得叶酸，但所需的量很少：我们发现即使细菌的叶酸大量减少，线虫也可以正常生长。事实上为了看到类似发育缺陷的情况，我们不得不使用特定的线虫突变体和低叶酸的细菌。这种叶酸缺乏症状可以通过添加亚叶酸（一种在自然界发现的叶酸）得到预防，但叶酸的效率要低得多。在本文中，我们证明叶酸需要通过大肠杆菌来防止发育缺陷。

这一结果是出乎意料的，因为大肠杆菌不能摄取叶酸。然而，它可以摄取叶酸的分解产物，即对氨基苯甲酰谷氨酸，并通过本文合著者之一Jacalyn Green发现的途径中，利用对氨基苯甲酰谷氨酸合成新的叶酸。对氨基苯甲酰谷氨酸存在于叶酸制剂中，包括从当地购买的片剂。叶酸经过复杂的分解过程，随后在细菌中再合成，然后被蠕虫吸收，确实可以防止叶酸缺乏，但我们也发现它也有负面影响，阻止了由低叶酸细菌引起的寿命延长。

这条途径是否存在于人类？分解产物存在于补充剂中，并且完整的叶酸可能在胃中进一步分解，但我们不知道对氨基苯甲酰谷氨酸与细菌接触的程度。其中大部分可能会在接触到胃肠道深处的细菌之前被吸收或代谢。这需要进一步实验验证。

叶酸被肠道细菌吸收是否安全？我们认为在有些情况下细菌叶酸含量的增加可能具有负面影响，例如与病原菌过度生长有关的慢性疾病，但这需要进一步研究。

在美国和加拿大等许多国家，叶酸被添加到面粉中。在其他国家，它被添加到人造黄油、谷物和其他食品中。叶酸的强制添加可以防止许多神经管先天缺陷，因为母亲需要足够的叶酸水平，甚至在怀孕之前。然而，有些人质疑，在并非每个人都需要叶酸的情况下，给所有人提供叶酸是否安全或合乎道德。

一些研究表明，叶酸可能对健康产生负面影响，如增加结肠癌风险或掩盖维生素B12缺乏症，但政府资助的专家小组通过文献综述得出的结论认为，补充叶酸是安全的。我们惊讶地发现这些综述没有考虑肠道微生物或叶酸的稳定性。我们希望该论文能够鼓励在这方面进行FC碰碰胡老虎机法典-提高赢钱机率的下注技巧的研究，并且引起公共卫生机构的注意。

摘要：

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.

阅读论文原文，请访问https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0534-3?utm_source=Other_website&utm_medium=Website_links&utm_content=DaiDen-BMC-BMC_Biology-Biology-China&utm_campaign=BMCF_USG_BSCN_DD_BMCBiology_folicacid

期刊介绍：BMC Biology is an open access journal publishing outstanding research in all areas of biology, with a publication policy that combines selection for broad interest and importance with a commitment to serving authors well.

2017 Journal Metrics

Citation Impact

5.770 - 2-year Impact Factor

7.556 - 5-year Impact Factor

3.425 - Source Normalized Impact per Paper (SNIP)

（来源：科学网）