Design, construction, and in vivo augmentation of a complex gut microbiome

Area of Science:

• Microbiology
• Gnotobiology
• Host-Microbe Interactions

Background:

• Modeling the human gut microbiome in mice is crucial for understanding host-microbe interactions.
• Previous models were either defined or complex, but not both, limiting their research utility.

Purpose of the Study:

• To construct and characterize a defined, complex bacterial community from human gut microbiota.
• To improve the stability and colonization resistance of microbial models in gnotobiotic mice.
• To create a model system for mechanistic interrogation of microbiome-associated phenotypes.

Main Methods:

• In vitro construction of a 104-species defined community (hCom1) from human gut taxa.
• Colonization of germ-free mice with hCom1, followed by challenge with human fecal samples.
• Iterative addition of engrafted species to create a more complex community (hCom2).
• Evaluation of hCom2 stability, colonization resistance against pathogenic E. coli, and phenotypic similarity to human fecal communities in gnotobiotic mice.

Main Results:

• hCom2 demonstrated increased stability against fecal challenge compared to simpler models.
• hCom2 provided robust colonization resistance against pathogenic Escherichia coli.
• Mice colonized with hCom2 or human fecal communities exhibited similar phenotypes.

Conclusions:

• The developed hCom2 model represents a significant advancement in creating defined, complex human gut microbial communities in mice.
• This model system is suitable for mechanistic studies investigating the impact of specific microbial species and genes on host-associated phenotypes.
• hCom2 offers a powerful tool for dissecting host-microbe interactions and microbiome functions.