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Microbiome. 2017 Aug 1;5(1):87. doi: 10.1186/s40168-017-0306-2.

Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning.

Author information

1
BioTechnology Institute, University of Minnesota, St. Paul, MN, USA.
2
Center for Immunology, University of Minnesota, 2101 6th St. S.E., Room 3-184, Wallin Medical Biosciences Building, Minneapolis, MN, 55414, USA.
3
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
4
Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
5
Department of Soil, Water, and Climate, University of Minnesota, St. Paul, MN, USA.
6
BioTechnology Institute, University of Minnesota, St. Paul, MN, USA. khoru001@umn.edu.
7
Center for Immunology, University of Minnesota, 2101 6th St. S.E., Room 3-184, Wallin Medical Biosciences Building, Minneapolis, MN, 55414, USA. khoru001@umn.edu.
8
Division of Gastroenterology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA. khoru001@umn.edu.

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.

KEYWORDS:

Antibiotics; Fecal microbiota transplantation; Germ-free; Humanization; Mouse model

PMID:
28760163
PMCID:
PMC5537947
DOI:
10.1186/s40168-017-0306-2
[Indexed for MEDLINE]
Free PMC Article

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