Abstract
BACKGROUND: Human microbiota-associated (HMA) animal models relying on germ-free recipient mice are being used to study the relationship between intestinal microbiota and human disease. However, transfer of microbiota into germ-free animals also triggers global developmental changes in the recipient intestine, which can mask disease-specific attributes of the donor material. Therefore, a simple model of replacing microbiota into a developmentally mature intestinal environment remains highly desirable.
RESULTS: Here we report on the development of a sequential, three-course antibiotic conditioning regimen that allows sustained engraftment of intestinal microorganisms following a single oral gavage with human donor microbiota. SourceTracker, a Bayesian, OTU-based algorithm, indicated that 59.3 ± 3.0% of the fecal bacterial communities in treated mice were attributable to the donor source. This overall degree of microbiota engraftment was similar in mice conditioned with antibiotics and germ-free mice. Limited surveys of systemic and mucosal immune sites did not show evidence of immune activation following introduction of human microbiota.
CONCLUSIONS: The antibiotic treatment protocol described here followed by a single gavage of human microbiota may provide a useful, complimentary HMA model to that established in germ-free facilities. The model has the potential for further in-depth translational investigations of microbiota in a variety of human disease states.
Original language | English (US) |
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Pages (from-to) | 87 |
Number of pages | 1 |
Journal | Microbiome |
Volume | 5 |
Issue number | 1 |
DOIs | |
State | Published - Aug 1 2017 |
Bibliographical note
Funding Information:This work was supported by a Minnesota’s Discovery, Research and Innovation Economy grant to the University of Minnesota (AK, MJS), NIH grant 1R21-AI114722–01 (AK, MJS), and philanthropic support from Achieving Cures Together (AK, MJS), and the Hubbard Foundation (AK).
Keywords
- Antibiotics
- Fecal microbiota transplantation
- Germ-free
- Humanization
- Mouse model