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Table 2 Examples of successfully conducted microbiota transplantation experiments into germ-free (GF) recipient animals

From: From meta-omics to causality: experimental models for human microbiome research

Animal model Host microbiota aGF status versus CONV-Rbanimals Donor’s microbiota in the recipient animal
Zebrafish Predominantly Proteobacteria (82% ± 22%) and Fusobacteria (11% ± 15.2%). Minor populations are: Firmicutes, Bacteroidetes, Verrucomicrobia, Actinobacteria, candidate phyla TM6 and TM7, Planctomycetes, Nitrospora and candidate division OP10 [53, 54]. Reduced rates of epithelial proliferation [53]. Mouse to zebrafish: predominantly Firmicutes and Bacteroides[51]; when GF zebrafish are colonized with mouse microbiota the transplanted community resembles its community of origin in terms of the lineages present, but the relative abundance of the lineages changes to resemble the normal gut microbial community composition of the recipient host. Thus, a selective pressure of the host is imposed to the recipient’s gut habitat [54].
Compromised ability to use nutrients [53].
Mouse Mouse and human microbiota are similar at the phylum level, but different at the genus level (>99% of the bacterial phylogenetic types from wild-type mice belong to two divisions: Firmicutes and Bacteroidetes) [51]. Most widely used GF animal model and theoretically any mouse strain can be derived to GF status. Human to mouse : Transplantation of fresh or frozen adult human fecal microbial communities into GF mice results in stably and heritably colonized mice with a microbiota that reproduces much of the bacterial diversity of the donor’s microbiota (all bacterial phyla, 11/12 bacterial classes, and 88% (58/66) of genus-level taxa) [55, 56].
Numerous immunological differences in GF animals: Peyer’s patches are poorly formed; composition of CD4+ T cells and IgA-producing B cells in the lamina propria is altered [5763]; impaired development of follicular B- and T-cell areas of the spleen and peripheral lymph nodes [60]. Th17 and Treg CD4+ T cells are less efficient in GF mice [6163].
The epithelial cell turnover is decreased by a factor 2 in GF animals compared to CONV-R mice [64, 65]. Obese mouse to GF mouse : Microbiota transplantation experiments utilizing genetically obese ob/ob mice [66],CONV-R mice fed a Western diet [67], and mice lacking the Toll like receptor 5 [68] have demonstrated that colonization with an obesity-associated gut microbiota results in an increased gain in adiposity relative to colonization with a gut microbiota harvested from lean controls.
Postnatal gene expression of β1-4-galactosyltransferase stays at low levels in GF mice [69] and in general host gene expression differs between GF and colonized mice [70].
Compromised ability to use nutrients in GF animals compared to CONV-R mice [60]. Pig to mouse : when GF mice are colonized with pig microbiota the overall bacterial group distributions are similar, but colony and cell morphologies of bacteria grown on specific media are different between pig and gnotobiotic mice [71].
Difference in metabolic signatures in GF mice compared to CONV-R mice and humans [72, 73].
Rat Rat and human microbiota are similar at the phylum level but different at the genus level (wild-type rat microbial communities harbor at least eight different divisions dominated by two major phyla: Firmicutes (74%) and Bacteroidetes (23%)) [74]. Difference in metabolic signatures [7581]. Human to rat : when GF rats are colonized with human microbiota the transplanted community resembles its community of origin in terms of the group or genus levels but differences at the dominant species level occur. Thus, a selective pressure of the host is imposed on the gut habitat [82]. However, certain metabolic characteristics (high equol-producing and low equol-producing status or cholesterol-to-coprostanol conversion) of human intestinal floras can be transferred to GF rats [82, 83].
In CONV rats, the colonic mucus layer is twice as thick as in GF rats [84], and the mucin chemical composition is altered [85, 86].
Numerous immunological defects; the proportion of intraepithelial CD4+ and CD8+ T cells is altered [59, 87], as well as the composition and T cell receptor repertoire [59].
Decreased enterocyte production [88].
Pig The microbiome of pigs is dominated by two major phyla: Firmicutes (≈81%) and Bacteroidetes (≈11%) [89, 90]. Host gene expression differs between GF and colonized pigs [91]. Human to pig : pigs seem to induce less host specific selection of the donor microbiota [92].
Epithelial cell proliferation and differentiation genes are downregulated in GF piglets compared to CONV-R pigs [91]. CONV-R pigs to GF pigs: Genes involved in biological processes such as epithelial cell turnover, nutrient transport and metabolism, xenobiotic metabolism, JAK-STAT signaling pathway, and immune responsiveness become upregulated by the colonization of GF pigs [91].
  1. aGF, germ-free.
  2. bConv-R, conventionally raised.