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。 叶酸摄入量低与现代遗传猪种生长缓慢和奶牛产奶量下降有关。 由于在加拿大的食品供应中添加叶酸，妇女叶酸摄入量有所增加，导致严重的出生缺陷（如神经管缺陷）减少了50%。 然而，较高的叶酸合成形式（即。添加到食物或动物饲料中，或在维生素补充剂中提供的叶酸与许多有害结果有关。 在哺乳动物现在消耗的水平上，叶酸可以延迟维生素B12缺乏症的诊断，甚至使其变得更糟。 维生素B12缺乏症很常见，可导致神经系统损伤，如果不迅速纠正，可能是不可逆的。高摄入量的叶酸也被认为会促进某些类型的癌症。 更好地了解叶酸营养“输入侧”背后的生物学将有助于制定在益处和风险之间取得正确平衡的饮食建议。 我们的研究探讨了细菌合成叶酸对这个方程的“输入端”的贡献。 与动物不同，许多通常存在于结肠中的细菌可以产生叶酸。 我们发现，哺乳动物结肠中叶酸的含量可以超过膳食需求，是一种可以被吸收的形式，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叶酸被吸收的比例，更好地了解结肠中叶酸储存库背后的生物学。 此外，我们将评估常见饮食情景的影响（例如，低或高叶酸摄入量，使用益生菌）对结肠叶酸吸收的影响，并观察这如何在分子水平上影响结肠中的叶酸转运蛋白。 这项工作将导致了解细菌合成的叶酸在结肠中的可用性和调节其供应的因素。 从长远来看，它可能会导致创新的策略，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.