Folate, methylation and cancer: more than just a gut feeling?!

Folate and other B-vitamins are essential for a healthy life. However, the optimal folate status with regard to human health remains controversial. A folate deficiency has been associated with an increased risk of cancer of the large intestine (colorectal cancer). An excessive intake of synthetic folate (folic acid), however, may also increase colorectal cancer risk. In the light of cancer prevention, further insights into causal mechanisms that link folate to cancer risk are urgently needed.

Bacteria as folate suppliers

Human cells are not able to produce folate and are therefore depending on other sources such as diet. Notably, several bacteria in the human large intestine also synthesize folate. The large intestine therefore represents a substantial local folate source. To what extent bacterial folate production is relevant for human health is not fully understood.

DNA methylation

Folate mediates a biochemical process called one-carbon metabolism and provides methyl groups for DNA methylation. DNA methylation can determine gene activity. Several studies showed that intake of folate is associated with DNA methylation of cancer-related genes. So far, little attention has been paid to intestinal folate sources in relation to disease mechanisms. This raises the question whether bacterial biosynthesis of folate is involved in regulation of DNA methylation. We aim to better understand the relation between folate-producing bacteria, folate levels and DNA methylation in the large intestine. Experimental animal and observational human studies will be applied to fully characterize the role of intestinal folate sources in relation to DNA methylation.

Disease mechanisms

This research aims to shed further light on the hypothesis that intestinal folate sources are important for regulation of DNA methylation. This information enhances a better understanding of potential disease mechanisms in the large intestine.