Elucidating principles of microbiome spatial organization using synthetic gut communities

The human digestive tract contains complex communities of microbes that contribute to human health by facilitating nutrient metabolism and digestion, promoting immune function, and providing protection against pathogens. To provide these human health benefits, microbial communities must be able to colonize and persist in the human digestive tract. This project will analyze several factors that are important for assembly and stability of these communities, and will provide tools that the scientific community can use for future studies. This project will inform microbial engineering efforts and perhaps lay the groundwork for future biomedical applications. Beyond the research community, the project will engage the public through hands-on microbiome workshops where participants learn about and study microbial communities. Microbial communities are essential for human health, environmental processes, and biotechnology, yet the basic rules that govern their assembly, stability, and function remain unclear. This project will develop a defined synthetic human gut microbiome, called SynhCom, created from a curated set of common and ecologically important gut bacteria. Using gnotobiotic mice, the research will systematically examine how spatial organization and biofilm formation influence the persistence and resilience of microbial communities under changing conditions such as diet. High resolution spatial metagenomics, functional genomics, and biofilm characterization will be used to uncover the mechanisms that shape microbial interactions and host responses. Unlike studies of natural, complex microbiomes that make it difficult to identify cause and effect, SynhCom provides a reproducible and controlled model to directly test community-level principles. The findings will establish a framework for understanding microbial ecosystems that could be applied to different settings, from the human gut to soil and aquatic environments. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.