Factors Affecting Folate Absorption Across the Colon

叶酸是维生素B的一种，促进RNA和DNA的生物合成，以及同型半胱氨酸的修复和转化为蛋氨酸，蛋氨酸是一种必不可少的氨基酸。蛋氨酸可用于制造蛋白质或转化为S-腺苷蛋氨酸，这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。在生命周期的合成代谢阶段，包括妊娠、哺乳以及早期胎儿和出生后，叶酸的需求量最高。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，结肠中储存了大量的叶酸，通常超过了食物的摄入量，细菌分泌的形式可以被大量吸收。结肠菌的组成可以通过饮食因素来控制，比如纤维，它们逃脱了小肠的消化，并被发酵。我们在未来5年的目标是更彻底地了解人类结肠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意义。我们将通过量化两种主要的叶酸转运蛋白(PCFT，RFC)的mRNA和蛋白质水平来实现这一点，我们假设这两种转运蛋白与结肠中叶酸的吸收和运输有关。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的将叶酸转化为可利用的单谷氨酰胺形式的酶(叶酸结合气体)的浓度，来评估生物可利用性较低的叶酸来源(来自脱落细胞和死亡细菌的多聚谷氨酸化叶酸)的可用性。最后，我们将检验益生菌改变微生物叶酸合成和吸收的能力。这项工作将导致对结肠叶酸代谢和吸收的更深入了解，从而产生更合适的叶酸饮食建议。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：对可能产生天然叶酸而不是合成叶酸的饮食来源的乳制品进行细菌培养选择，改善叶酸营养以促进现代猪遗传品系的生长，更早地培育成功和减少奶牛的难产，以及提高鸡的蛋产量。在人类中，母亲叶酸摄入量的改善降低了加拿大严重出生缺陷的风险，包括神经管缺陷。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。

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.