Factors Affecting Folate Absorption Across the Colon

影响结肠中叶酸吸收的因素

• 批准号: RGPIN-2015-06232
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=661118
• 关键词: Factors; Affecting; Folate; Absorption; Across

Folate, one of the B vitamins, facilitates RNA and DNA biosynthesis and repair and conversion of homocysteine to methionine, an essential amino acid. Methionine can be used to make protein or converted to S-adenosylmethionine, a molecule involved in numerous important methylation reactions in the body including the synthesis of hormones and neurotransmitters. Folate requirements are highest during anabolic stages of the life-cycle including gestation, lactation and early fetal and postnatal life. As humans can't synthesize folate, it was assumed that mammals solely obtained folate from the diet or vitamin supplements. Our NSERC-funded research program changed this understanding-we showed that the colon stores a large depot of folate often exceeding dietary intake, and the form secreted by bacteria can be absorbed in large quantities. The makeup of colonic bacteria can be manipulated by dietary factors, such as fibre, that escape digestion in the small intestine and are fermented. Our goal over the next 5 years is to develop a more thorough understanding of the fundamental processes involved in folate metabolism and absorption in the colon of humans and to continue to assess its significance to whole body folate metabolism and at the level of the colon cells. We will do this by quantitating mRNA and protein levels of two major folate transporters (PCFT, RFC) that we hypothesize are responsible for folate absorption and transport in the colon. We will study the effect of folic acid supplements on the presence of unmetabolized folic acid in the colon, the expression of PCFT and RFC and colonic folate absorption. We will also assess the availability of less bioavailable sources of folate (polylglutamylated folates from sloughed cells and dead bacteria) by measuring the concentrations of enzymes (folate conjugases) in the colon that are known to convert these folates to their available monoglutamyl form. Finally, we will examine the ability of probiotics to modify microbial synthesis of folate and absorption. This work will lead to a deeper understanding of colonic folate metabolism and absorption that will result in more appropriate dietary folate recommendations. Further, this work will inform current areas of research with high potential economic impact on the agri-foods sector, including: bacterial culture selection for dairy products that may yield a natural, versus synthetic, dietary source of folate, improving folate nutrition to enhance growth in modern genetic strains of swine, earlier breeding success and reduced dystocia in dairy cows, and increased egg yield in chickens. In humans, improved maternal folate intake has reduced the risk of serious birth defects in Canada, including neural tube defects. 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.

叶酸是一种B族维生素，它能促进RNA和DNA的生物合成，修复和将同型半胱氨酸转化为蛋氨酸，蛋氨酸是一种必需氨基酸。甲硫氨酸可用于制造蛋白质或转化为S-腺苷甲硫氨酸，S-腺苷甲硫氨酸是一种参与体内许多重要甲基化反应的分子，包括激素和神经递质的合成。叶酸的需求量在生命周期的合成代谢阶段是最高的，包括妊娠期、哺乳期和胎儿早期和产后生命。 由于人类不能合成叶酸，人们认为哺乳动物只能从饮食或维生素补充剂中获得叶酸。 我们的NSERC资助的研究项目改变了这种理解-我们表明结肠储存了大量的叶酸，通常超过饮食摄入量，并且细菌分泌的形式可以被大量吸收。结肠细菌的组成可以通过饮食因素来控制，例如纤维，这些纤维在小肠中逃脱消化并发酵。我们未来5年的目标是更深入地了解人体结肠中叶酸代谢和吸收的基本过程，并继续评估其对全身叶酸代谢和结肠细胞水平的重要性。我们将通过定量两种主要叶酸转运蛋白（PCFT，RFC）的mRNA和蛋白水平来实现这一点，我们假设这两种转运蛋白负责结肠中叶酸的吸收和转运。我们将研究叶酸补充剂对结肠中未代谢叶酸的存在、PCFT和RFC的表达以及结肠叶酸吸收的影响。 我们还将通过测量结肠中已知将这些叶酸转化为其可用的单谷氨酰形式的酶（叶酸结合物）的浓度，评估生物利用度较低的叶酸来源（来自脱落细胞和死细菌的聚谷氨酸化叶酸）的可用性。 最后，我们将研究益生菌的能力，以修改微生物合成叶酸和吸收。这项工作将导致更深入地了解结肠叶酸代谢和吸收，这将导致更适当的饮食叶酸的建议。此外，这项工作将为当前对农业食品部门具有高潜在经济影响的研究领域提供信息，包括：乳制品的细菌培养选择，这些乳制品可能产生天然与合成的叶酸膳食来源，改善叶酸营养以增强现代遗传猪株的生长，奶牛的早期育种成功和减少难产，以及增加鸡的产蛋量。在加拿大，改善孕妇叶酸摄入量降低了严重出生缺陷的风险，包括神经管缺陷。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。