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

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.
• 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.