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We are constantly exposed to foreign DNA from various sources like benign or malicious microbes in and on our body, pollens in the inhaled air and as the largest amount with the daily food supply. DNA molecules are ubiquitous in large numbers in all raw and unprocessed food. Depending on the extent of processing, various fractions of DNA molecules of varying size may be present in the consumed product, even in processed food such as corn chips and chocolate.

Uptake and fate of foreign DNA ingested with the daily food intake in the gastrointestinal tract of mammals is not a completely understood topic. Though exogenous nucleotides are essential at least for maintaining host immunity to allergenic tissues and restoring specific immune responses to foreign antigens, the amount of DNA in food is relatively low compared to other constituents and does not have significant nutritional value, hence nutritional studies rarely deal with this issue. The final step of uptake of nucleotides in the epithelium of the gastrointestinal tract is a relatively well understood complex process. In contrast, the comprehension of the degradation process of long chains of DNA and possible uptake of larger fragments face many methodological challenges and very few studies have been conducted on the digestion of food-derived DNA within the 68 m long digestive tract of adult humans. Animal feeding studies have demon- strated that a minor amount of fragmented dietary DNA may resist the digestive process (for a recent review see) and there are sporadic reports in the literature claiming that orally administered small fragments of bacterial DNA or plant RNA can transgress the intestinal barrier, but no studies have explored the question if large DNA segments can pass from natural food intake to the circulatory system.

Blood is not free of DNA. White blood cells have nuclei that contain genetic material, which gives the dominant part of the DNA in a full blood sample. Beyond the DNA contained in the white blood cells the cell free blood plasma contains DNA, too. This is the so called circulating cell-free DNA (cfDNA) which is an ideal target to test the presence of foreign DNA, since most of the human ”background” is removed by the cellular fraction.

Characteristics of Cell-free DNA

Circulating cell-free DNA (cfDNA) is defined as extracellular DNA occurring in body fluids was discovered in the human bloodstream and first described in 1948 by Mandel and Metais, but its origin and possible role is still controversial. The cfDNAs are mostly double-stranded molecules with fragment size in a wide range from 180 bp up to 21 kbp. The shorter fragments are thought to be related to the histone octamer structure and apoptotic degradation process, while necrosis results much larger fragments. Through phagocytosis of apoptotic cells macrophages may release the degraded DNA fragments into the bloodstream. These cfDNA fragments circulate as nucleoprotein complexes and in healthy individuals, the main part of cfDNA is found adsorbed to the surface of blood cells