The establishment of human fecal microbes within animals, provides the opportunity for the study of a microbiota of human origin within these animals. Human flora associated animals (HFA) have proven to be particularly valuable in studies of the metabolic and immunological activities of the human microbiota. Athough HFA animals are valuable for investigations related to the human microbiota, several differences between animal and human physiology may influence colonization by the human microbiota in animal hosts. Such differences may promote host-specific colonization by microorganisms in different animals (92,93). As a result, microbes of human origin may be disadvantaged in the animal GIT, compared to isolates originating from this particular animal species.
HFA animals are created by inoculating germ-free animals with a human fecal homogenate (94). The resulting microbial profile of HFA animals is partly dependent on the differing ability of the various microorganisms in the human fecal sample to colonize the animal GIT. Previous studies have shown that certain microorganisms of human fecal origin were unable to colonize the rodent GIT (95). There may be several reasons for this, such as diets or host factors like transit times and physiological conditions. It has been demonstrated that mice, fed with a commercially available animal feed, may have a reduced, or even undetectable level of bifidobacteria in feces. However, after feeding these mice an alternative diet for several weeks, bifidobacteria could be detected in the mice that were fed sucrose or amylose, with particularly dense populations of bififodobacteria observed in mice that were fed with an amylose rich diet (Fig. 2). This suggests that diet, and specifically dietary ingredients such as certain carbohydrates, are important for the composition of the GI microbota and that previously nondetectable microbial groups may be stimulated to detectable levels. Consideration may be given to the possibility that the growth of microbal populations due to dietary intervention, may be at the expense of less competitive microbial groups.
The colonization of human originated bifidobacteria within germ-free animals is not always successful (95). Hiramaya and co-workers (96) demonstrated that in rodents, the source of fecal material containing bifodobacteria influences the ability of bifodobacteria to colonize the GIT (95). This may be due to the fact that bifodobacteria from different sources possess different natural characteristics. The activity of the human source microbiota that is contained within HFA animals may also be dependent on the cultural origin and dietary habits of the human source (97,98). For instance, fecal material obtained from different human donors has been shown to provide a different degree of effectiveness in protection against Salmonella (32). Although this type of model provides a good tool for studying the effects of the human microbiota, it cannot be assumed that the microbial profile of HFA animals is identical to that of the human donor.
HFA rodents are useful in studies of the metabolic activity of the human microbiota. The effects of microbiota on the metabolism of lignans and isoflavones have been investigated in studies using germ-free and HFA rats (98). In similar studies, HFA rats have been used to assess the metabolism of dietary fats (99,100). The usefulness of HFA animals has also been illustrated in studies such as those conducted on the effect of complex carbohydrates on the human microbiota, including the effect of resistant starch (97). Other studies include those relating to the production of short chain fatty acids (85,101) and microbial enzyme activities (102). HFA animals are also valuable for toxicological studies. There are several examples of studies in which HFA animals have been used to assess the effect of the human microbiota on potentially carcinogenic compounds (47,103). Interestingly, both studies indicated that the source of fecal material used to create HFA rats influenced the transformation of pre-carcinogens to carcinogenic componds.
Oozeer and colleagues (28) used a genetically modified L. casei strain to assess whether the strain was active throughout the passage of the intestinal tract of HFA mice. This strain was modified by the introduction of genes coding for erythromycin resistance and luciferase. Results from this study indicate that this strain is both metabolically active and able to initiate new protein synthesis during its transit through the GIT. Techniques in transcriptomics and metabolomics are paving the ways for new studies on microbial activity of the gut contents and detailed studies of biochemical properties of host cells lining the GI epithelium.
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