Human Flora-Associated (HFA) Animals for Studying the Role of Intestinal Flora in Human Carcinogenesis

抄録

Although the intestinal flora is thought to have a critical role in carcinogenesis, there is little information regarding the role of the human intestinal flora on the effects of dietary and environmental mutagens in vivo. By inoculating germfree animals with feces, the major composition of human flora can be transferred into the ex-germfree animals, i.e. human flora-associated (HFA) animals. The HFA animals provide a stable tool for studying the ecosystem and metabolism of human intestinal flora, though they have some limitations as a model. The capacity of human feces to activate or inactivate mutagens could be transferred into HFA mice and the presence of an intestinal flora was essential for the activity of feces against the mutagens. DNA adduct formation after the administration of dietary and environmental mutagens to mice with different bacterial conditions, including HFA mice, were then analyzed as an in vivo biomarker of cancer risk, and the results indicate that the intestinal flora have an active role in DNA adduct formation. It has also been demonstrated that the role of human intestinal flora is different from that of experimental animals in vivo as well as the metabolic activities against mutagens in vitro. Studies using HFA animals should provide much needed information of relevance to humans regarding the role of intestinal flora in carcinogenesis in vivo. The HFA animals could then contribute to prevention strategies for cancer involving improvement of the intestinal flora.