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

补充叶酸对结肠叶酸的利用率和吸收的影响

• 批准号: RGPIN-2020-04073
• 负责人: OConnor, Deborah
• 金额: $ 2.91万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761551
• 关键词: Impact; folic; acid; supplementation; availability

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.

叶酸是一类B族维生素化合物的总称，它们具有相似的结构，并促进新陈代谢过程中单个碳单位的转移。在这样做的过程中，叶酸对RNA和DNA的合成和修复以及必需氨基酸蛋氨酸的产生至关重要。叶酸还参与生命早期的“表观遗传编程”，即基因表达的修饰。这种维生素的合成形式叶酸被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)。叶酸不是在体内产生的，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支持的研究项目改变了这种理解，证明了叶酸可以由肠道细菌产生并通过结肠壁吸收。我们发现，叶酸的这种来源可能在满足哺乳动物对叶酸的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的吸收以及补充叶酸对这一过程的影响的了解。为此，我们将描述两种不同的转运蛋白在成人小肠和大肠不同区域的存在：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。鉴于最近有人关注到，大量摄入叶酸的一些不良影响可能是由于叶酸从肠道到血液的运输发生了变化，我们将研究补充叶酸对结肠中PCFT和RFC表达的影响。初步数据显示，高水平的叶酸也可能引起肠道细菌的变化，因此我们还将研究补充叶酸对结肠内容物中微生物丰度和多样性的影响。这项工作将有助于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。这将使加拿大人能够在当前食品环境的背景下制定叶酸和补充剂的膳食建议，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在农业食品领域进行叶酸研究，这些领域具有很高的潜在经济影响，如改善猪的生长，促进奶牛的早期繁殖成功和减少奶牛的分娩困难，以及提高鸡的蛋产量。在从事这项研究的过程中，我们将在最先进的设施中培养高素质的人员，以成为明天营养和自然科学界的领导者。