Factors Affecting Folate Absorption Across the Colon

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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.