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

Abstract

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.

Short-Chain Fructo-Oligosaccharides Modulate Intestinal Microbiota and Metabolic Parameters of Humanized Gnotobiotic Diet Induced Obesity Mice

“…These humanized gnotobiotic mice harbour a microbiota with the same composition and metabolic activities as a human microbiota that is rather stable over time to allow testing the diet effects, including the addition of fermentable oligosaccharides [20], on the composition of the microbiota.…”

“…A 10 −2 dilution of this stool was administered to 48 germ-free (GF) male C57BL/6J 4-week old mice (initial body weight 20.6±2.9 g) as previously described [19]. As the major components of the human microbiota can be transferred into the ex-germfree animals, these animals are considered the better model to investigate interactions between human intestinal microbiota, host factors and dietary manipulations [19], [20]. Mice were kept in sterile Plexiglas isolators, 3 per cage, at ANAXEM, the GF animal facilities of Micalis Institute (INRA, Jouy-en-Josas, France) for the 10-week duration of the study and had ad libitum access to irradiated feeds and sterile water.…”

“…Therefore we aimed at investigating whether other bacterial groups modulated by the ingredient are correlated with host metabolism by using a humanized mice model. This model provides a reliable microbiota stability over time and can be used to test the effects of different diets, including the addition of fermentable oligosaccharides, on the composition of the microbiota [19], [20]. The effect of scFOS will be particularly studied in a high fat diet known to induce obesity and impair glucose metabolism [21].…”

Gut microbiota and liver disease

“…Although these models more closely resemble the human situation than the mono‐ or bi‐ and poly‐associated models, these may still not fully replicate the human situation. For instance, feces from humans and human flora‐associated animals differ significantly in concentration of short‐chain fatty acids, despite being similar in several other characteristics …”

Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities

“…Inoculation of germ-free rodents with a human faecal microbiota, human-microbiota associated (HMA) animals, effectively mimics human microbial metabolism and thus provides a reliable model to study the human gut microbial ecosystem as well as metabolism (Hirayama & Itoh, 2005;Turnbaugh & Gordon, 2009). Some HMA rodent studies on catechin and isoflavone metabolism have been performed, but without investigating the effects on composition and activity of the microbial community itself (Bowey et al, 2003;Lhoste et al, 2003).…”