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

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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.