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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Bacteria / isolation & purification
  • Fecal Microbiota Transplantation
  • Feces / microbiology
  • Gastrointestinal Microbiome*
  • Germ-Free Life
  • Humans
  • Mice
  • Microbiota*
  • Models, Animal*


  • Anti-Bacterial Agents