The physiological significance of microbial synthesized folate and the impact of dietary manipulation on uptake

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Folate is a B-vitamin that helps to transfer one-carbon units in the body. This is required for DNA synthesis and repair and by all cells for growth and cell division. Low folate intake is associated with slower growth in modern genetic strains of swine, and decreased milk production in dairy cows. An improvement in the folate intake of women, as a result of folic acid fortification of the food supply in Canada, has led to a 50% reduction in serious birth defects (e.g. neural tube defects). However, higher intakes of folate in the synthetic form (ie. folic acid) added to foods or animal feeds, or provided in vitamin supplements is associated with a number of harmful outcomes. At levels now consumed by mammals, folic acid can delay the diagnosis of vitamin B12 deficiency or even make it worse. Vitamin B12 deficiency is common and can result in neurologic damage, which could be irreversible if not quickly corrected. High intakes of folic acid are also known to promote certain types of cancer. A better understanding of the biology behind the ''input side'' of folate nutrition will help to set dietary recommendations that strike the right balance between benefits and risks. Our research explores the contribution of bacterially synthesized folate to the "input side" of this equation. Unlike animals, many bacteria that commonly reside in the colon can make folate. We showed that the amount of folate in the mammalian colon can exceed dietary requirements, is in a form that can be absorbed, and is not associated with harmful effects. In the next 5 years we will develop a better understanding of the biology behind the depot of folate in the colon by determining what proportion is of bacterial origin, and how much of microbial folate is absorbed. Further, we will assess the impact of common dietary scenarios (eg. low or high folic acid intake, use of probiotics) on absorption of colonic folate, and see how this affects folate transporters in the colon at a molecular level. This work will lead to an understanding of the availability of bacterially synthesized folate in the colon and the factors regulating its supply. Longer-term it could lead to innovative strategies to provide folate in a quantity and form less likely to be associated with negative health outcomes compared to folic acid.