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Updated: Jun 30, 2026

A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System

Published on: August 30, 2019

A gavage-fomite based method to generate mouse models with natural microbiota.

Geongoo Han¹, Mohammad H Hasan¹, Olumide Adesioye¹

¹Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912.

Biorxiv : the Preprint Server for Biology

|June 29, 2026

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Introducing a novel gavage-fomite (GaF) method, this study enhances specific pathogen-free (SPF) mice with natural microbiota. GaF-treated mice show improved immune maturation and human-like immune traits, advancing immunological research.

Area of Science:

Immunology
Microbiology
Translational Research

Background:

Specific pathogen-free (SPF) mice are crucial for immunology but lack microbial exposure, limiting their predictive value for human clinical outcomes.
Sanitized housing environments prevent essential microbial exposure for proper immune maturation in laboratory mice.
Existing methods to introduce microbes, like pet store cohousing, have high variability and mortality.

Purpose of the Study:

To develop a novel method for introducing diverse microbial communities to SPF mice.
To generate mouse models with 'natural microbiota' that better mimic human immune development.
To improve the reliability of mouse models in immunological and translational research.

Main Methods:

Development and application of the gavage-fomite (GaF) method for microbial exposure.

Keywords:

Antigen-experienced CD8 T cells Immune maturation Microbial exposure Mouse models with natural microbiota

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Comparison of GaF method with pet store mice cohousing approach.

Analysis of gut microbial composition, immune cell distribution, cytokine levels, and gene expression in treated mice.

Main Results:

The GaF method consistently introduced diverse pathogens and commensals, similar to cohousing but with reduced mortality.
GaF-treated mice displayed consistent gut microbiota and robust immune maturation, including mucosal T-cell distribution and elevated cytokines.
Immune transcriptional signatures in GaF mice aligned closely with adult humans, and they showed enhanced protection against bacterial challenge.

Conclusions:

The gavage-fomite (GaF) method effectively generates mouse models with 'natural microbiota' and human-like immune traits.
GaF-treated mice exhibit improved immune maturation and enhanced disease resistance.
This method offers a simple, effective, and reproducible approach for advancing immunological research across institutions.