Impact of folic acid supplementation on availability and absorption of colonic folate

叶酸是B族维生素化合物的总称，它们具有相似的结构，并在代谢过程中促进单碳单位的转移。在此过程中，叶酸对于RNA和DNA的合成和修复以及必需氨基酸甲硫氨酸的产生至关重要。叶酸还参与“表观遗传编程”，即生命早期基因表达的改变。维生素的合成形式叶酸用于补充剂和强化食品中，以预防人类的出生缺陷（即神经管缺陷）。叶酸不能在体内产生，因此必须由外部来源提供。传统上，人们认为食物和补充剂是获得叶酸的唯一方法。我们的NSERC支持的研究计划改变了这种理解，证明叶酸可以由肠道细菌产生并通过结肠壁吸收。我们表明，这种叶酸来源可能在满足哺乳动物的叶酸需求方面起着重要作用。我们在未来5年的目标是提高我们对叶酸在结肠中吸收的理解，以及叶酸补充剂对这一过程的影响。为此，我们将表征成人小肠和大肠不同区域中存在的2种不同转运蛋白：质子偶联叶酸转运蛋白（PCFT）和还原叶酸载体（RFC）。我们还将测量结肠中将叶酸从不可吸收形式转化为可吸收形式的酶。鉴于最近的关注，高摄入量的叶酸的一些不良影响可能是由于叶酸从肠道运输到血液中的变化，我们将研究叶酸补充对结肠中PCFT和RFC表达的影响。初步数据表明，高水平的叶酸也可能引起肠道细菌的变化，因此我们还将研究叶酸补充剂对结肠内容物中微生物丰度和多样性的影响。这项工作将导致更深入地了解叶酸在结肠中的代谢和吸收，以及细菌合成的叶酸对哺乳动物叶酸需求的贡献。这将有助于在目前的食品环境下为加拿大人制定膳食叶酸和补充剂建议，在满足要求和不安全水平之间取得适当的平衡。此外，这项工作将有助于当前农业食品领域的叶酸研究领域，这些领域具有很高的潜在经济影响，例如改善猪的生长，促进奶牛的早期育种成功和减少分娩困难，以及增加鸡的产蛋量。在这项研究的追求，我们将培养高素质的人才在国家的最先进的设施，成为未来的营养和自然科学界的领导者。

Folate is a generic term for a family of B-vitamin compounds that share a similar structure and facilitate transfer of single carbon units during metabolism. In doing so, folates are critical for RNA and DNA synthesis and repair, and production of the essential amino acid, methionine. Folate is also involved in `epigenetic programming', the modification of gene expression, early in life. The synthetic form of the vitamin, folic acid, is used in supplements and in fortified foods for prevention of birth defects (i.e. neural tube defects) in humans. Folate is not produced within the body, and so must be provided by an outside source. Traditionally, it was assumed that food and supplements were the only methods of obtaining folate. Our NSERC-supported program of research has changed this understanding, demonstrating that folate can be produced by intestinal bacteria and absorbed through the wall of the colon. We showed that this source of folate likely plays a significant role in meeting the folate requirements of mammals. Our goal over the next 5 years is to improve our understanding of folate absorption across the colon and the influence of folic acid supplementation on this process. To do this, we will characterize the presence of 2 different transport proteins in different areas of the small and large intestines of adult humans: proton coupled folate transporter (PCFT) and reduced folate carrier (RFC). We will also measure enzymes in the colon that convert folate from a non-absorbable form to an absorbable form. Given recent concerns that some adverse effects of high intakes of folic acid may be due to changes in folate transport from the intestine into the blood, we will study the effect of folic acid supplementation on the expression of PCFT and RFC in the colon. Preliminary data suggest that high levels of folic acid may also induce changes in intestinal bacteria, so we will also examine the impact of folic acid supplementation on the microbial abundance and diversity in the colonic contents. This work will lead to a deeper understanding of folate metabolism and absorption in the colon and contribution of bacterially synthesized folate to the folate requirements of mammals. This will enable the setting of dietary folate and supplement recommendations for Canadians, in the context of the current food environment, which strike the right balance between meeting requirements and unsafe levels. Further, this work will be useful in current areas of folate research in the agri-foods sector with high potential economic impact such as improving growth in swine, promoting early breeding success and reducing birthing difficulty in dairy cows, and increasing egg yield in chickens. In pursuit of this research, we will train highly qualified personnel in state-of-the-art facilities to become leaders in the nutrition and natural sciences community of tomorrow.