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Updated: Jul 30, 2026
A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System
Published on: August 30, 2019
Human microbiota-transplanted C57BL/6 mice and offspring display reduced establishment of key bacteria and reduced
Randi Lundberg1,2,3, Martin F Toft4,5, Stine B Metzdorff6
1Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1871, Frederiksberg C, Denmark. lundberg.randi@gmail.com.
Abstract:
Transplantation of germ-free (GF) mice with microbiota from mice or humans stimulates the intestinal immune system in disparate ways. We transplanted a human microbiota into GF C57BL/6 mice and a murine C57BL/6 microbiota into GF C57BL/6 mice and Swiss-Webster (SW) mice. Mice were bred to produce an offspring generation. 56% of the Operational Taxonomic Units (OTUs) present in the human donor microbiota established in the recipient mice, whereas 81% of the C57BL/6 OTUs established in the recipient C57BL/6 and SW mice. Anti-inflammatory bacteria such as Faecalibacterium and Bifidobacterium from humans were not transferred to mice. Expression of immune-related intestinal genes was lower in human microbiota-mice and not different between parent and offspring generation. Expression of intestinal barrier-related genes was slightly higher in human microbiota-mice. Cytokines and chemokines measured in plasma were differentially present in human and mouse microbiota-mice. Minor differences in microbiota and gene expression were found between transplanted mice of different genetics. It is concluded that important immune-regulating bacteria are lost when transplanting microbiota from humans to C57BL/6 mice, and that the established human microbiota is a weak stimulator of the murine immune system. The results are important for study design considerations in microbiota transplantation studies involving immunological parameters.
Insights
Transplanting human microbiota into germ-free mice poorly stimulates their immune system, losing key bacteria. Murine microbiota better colonizes mice, highlighting differences in host-microbe interactions.
Area of Science:
- Microbiome research
- Immunology
- Host-microbe interactions
Background:
- Germ-free (GF) mice transplanted with microbiota exhibit distinct immune responses based on the donor source (human vs. murine).
- Understanding these differences is crucial for designing accurate microbiota transplantation studies.
Purpose of the Study:
- To compare the engraftment and immune-stimulating capacity of human versus murine microbiota in GF mice.
- To assess the impact of microbiota source on host immune gene expression and plasma cytokine profiles.
Main Methods:
- Germ-free C57BL/6 mice were colonized with either human or C57BL/6 murine microbiota.
- Operational Taxonomic Units (OTUs) establishment and gene expression (immune-related, intestinal barrier) were analyzed.
- Plasma cytokines and chemokines were quantified.
Main Results:
- Lower engraftment (56%) of human OTUs compared to murine OTUs (81%) was observed.
- Key anti-inflammatory human bacteria (e.g., Faecalibacterium, Bifidobacterium) failed to colonize.
- Human microbiota recipients showed lower immune gene expression and altered cytokine profiles compared to murine microbiota recipients.
Conclusions:
- Human microbiota transplantation to mice results in the loss of crucial immune-modulating bacteria.
- The established human microbiota acts as a weak stimulator of the murine immune system.
- Significant differences exist in host immune response to human versus murine microbiota, impacting study design.
