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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614024
• 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B族维生素之一，促进RNA和DNA的生物合成和修复，并将同型半胱氨酸转化为必需氨基酸蛋氨酸。蛋氨酸可以用来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。叶酸的需要量在生命周期的合成代谢阶段最高，包括妊娠期、哺乳期、胎儿早期和产后。由于人类不能合成叶酸，所以人们认为哺乳动物只能从饮食或维生素补充剂中获取叶酸。我们的nserc资助的研究项目改变了这种认识——我们发现结肠储存了大量的叶酸，通常超过了饮食摄入量，而细菌分泌的叶酸可以被大量吸收。结肠细菌的组成可以通过饮食因素来控制，比如纤维，这些食物在小肠中没有被消化，而是被发酵。我们未来5年的目标是对叶酸代谢和人体结肠吸收的基本过程有更深入的了解，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体（PCFT， RFC）的mRNA和蛋白质水平来做到这一点，我们假设它们负责叶酸在结肠中的吸收和运输。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酶（叶酸偶联物）的浓度来评估低生物可利用性叶酸来源（从脱落的细胞和死细菌中提取的多谷氨酰叶酸）的可用性，已知这些酶可以将叶酸转化为可用的单氨酰基形式。最后，我们将研究益生菌对微生物合成叶酸和吸收的影响。这项工作将导致对结肠叶酸代谢和吸收的更深入的了解，从而产生更合适的膳食叶酸建议。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：可能产生天然叶酸而不是合成叶酸膳食来源的乳制品的细菌培养选择，改善叶酸营养以促进现代猪遗传品系的生长，早期育种成功并减少奶牛难产，以及提高鸡的产蛋量。在加拿大，在人类中，母亲叶酸摄入量的提高降低了严重出生缺陷的风险，包括神经管缺陷。为了进行这项研究，我们将在最先进的设施中培养高素质的人才，使他们成为未来营养和自然科学界的领导者。