Genome-scale metabolic model-guided systematic framework for designing customized live biotherapeutic products

Area of Science:

• Microbiology
• Systems Biology
• Bioengineering

Background:

• Live biotherapeutic products (LBPs) represent a promising class of microbiome-based therapeutics.
• The development of LBPs necessitates robust evaluation of their quality, safety, and efficacy.
• Characterizing complex microbial communities and their interactions with hosts is crucial for LBP success.

Purpose of the Study:

• To present a model-guided framework for the development of live biotherapeutic products (LBPs).
• To demonstrate the utility of genome-scale metabolic models (GEMs) in characterizing LBP candidate strains.
• To outline a strategy for screening, assessing, and designing personalized multi-strain LBPs using GEMs.

Main Methods:

• Utilizing genome-scale metabolic models (GEMs) to analyze metabolic capabilities of LBP candidate strains.
• Modeling metabolic interactions between LBP strains, commensal microbes, and host cells at a systems level.
• Developing a GEM-based strategy for the systematic evaluation and design of LBPs.

Main Results:

• The proposed GEM-guided framework enables comprehensive characterization of LBPs.
• GEMs facilitate the understanding of metabolic cross-talk between LBPs, microbiome, and host.
• The strategy supports the screening and design of tailored, multi-strain LBP formulations.

Conclusions:

• Genome-scale metabolic models offer a powerful systems-level approach for LBP development.
• This framework enhances the rigorous evaluation of LBP quality, safety, and efficacy.
• The presented strategy paves the way for personalized microbiome-based therapeutics.