The physiological significance of microbial synthesized folate and the impact of dietary manipulation on uptake

叶酸是一种b族维生素，有助于在体内转移一碳单位。这是DNA合成和修复以及所有细胞生长和细胞分裂所必需的。低叶酸摄入量与现代猪遗传品系生长缓慢和奶牛产奶量下降有关。由于在加拿大食品供应中强化叶酸，妇女叶酸摄入量有所改善，导致严重出生缺陷（例如神经管缺陷）减少了50%。然而，高摄入量的叶酸合成形式(即。叶酸)添加到食物或动物饲料中，或以维生素补充剂的形式提供，与许多有害后果有关。哺乳动物现在摄入的叶酸水平可以延缓维生素B12缺乏症的诊断，甚至使情况恶化。维生素B12缺乏症很常见，会导致神经损伤，如果不及时纠正，可能是不可逆转的。过量摄入叶酸也会促进某些类型的癌症。更好地了解叶酸营养“输入侧”背后的生物学原理，将有助于制定饮食建议，在益处和风险之间取得适当的平衡。我们的研究探索了细菌合成叶酸对这个等式的“输入方”的贡献。与动物不同的是，许多常住在结肠里的细菌可以制造叶酸。我们表明，哺乳动物结肠中叶酸的含量可以超过饮食需求，以一种可以被吸收的形式存在，并且与有害影响无关。在接下来的5年里，我们将通过确定细菌来源的比例以及微生物吸收的叶酸的多少来更好地了解结肠中叶酸储存背后的生物学原理。此外，我们将评估常见饮食方案的影响(例如：低叶酸或高叶酸摄入量，使用益生菌)对结肠叶酸吸收的影响，并观察这在分子水平上如何影响结肠中叶酸转运体。这项工作将有助于了解细菌在结肠中合成叶酸的有效性以及调节其供应的因素。从长期来看，它可能会导致创新的战略，提供叶酸的数量和形式，与叶酸相比，不太可能与负面健康结果相关。

Folate is a B-vitamin that helps to transfer one-carbon units in the body. This is required for DNA synthesis and repair and by all cells for growth and cell division. Low folate intake is associated with slower growth in modern genetic strains of swine, and decreased milk production in dairy cows. An improvement in the folate intake of women, as a result of folic acid fortification of the food supply in Canada, has led to a 50% reduction in serious birth defects (e.g. neural tube defects). However, higher intakes of folate in the synthetic form (ie. folic acid) added to foods or animal feeds, or provided in vitamin supplements is associated with a number of harmful outcomes. At levels now consumed by mammals, folic acid can delay the diagnosis of vitamin B12 deficiency or even make it worse. Vitamin B12 deficiency is common and can result in neurologic damage, which could be irreversible if not quickly corrected. High intakes of folic acid are also known to promote certain types of cancer. A better understanding of the biology behind the ''input side'' of folate nutrition will help to set dietary recommendations that strike the right balance between benefits and risks. Our research explores the contribution of bacterially synthesized folate to the "input side" of this equation. Unlike animals, many bacteria that commonly reside in the colon can make folate. We showed that the amount of folate in the mammalian colon can exceed dietary requirements, is in a form that can be absorbed, and is not associated with harmful effects. In the next 5 years we will develop a better understanding of the biology behind the depot of folate in the colon by determining what proportion is of bacterial origin, and how much of microbial folate is absorbed. Further, we will assess the impact of common dietary scenarios (eg. low or high folic acid intake, use of probiotics) on absorption of colonic folate, and see how this affects folate transporters in the colon at a molecular level. This work will lead to an understanding of the availability of bacterially synthesized folate in the colon and the factors regulating its supply. Longer-term it could lead to innovative strategies to provide folate in a quantity and form less likely to be associated with negative health outcomes compared to folic acid.