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bioRxiv · 10.1101/2022.03.14.484355

Model-guided design of the diversity of a synthetic human gut community

Connors, B. M.·Ertmer, S.·Clark, R. L.·Thompson, J.·Pfleger, B. F.·Venturelli, O. S.
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Abstract

Microbial communities have tremendous potential as therapeutics. However, a major bottleneck is manufacturing high-diversity microbial communities with desired species compositions. We develop a two-stage, model-guided framework to produce microbial communities with target species compositions. We apply this method to optimize the diversity of a synthetic human gut community. The first stage exploits media components to enable uniform growth responses of individual species and the second stage uses a design-test-learn cycle with initial species abundance as a control point to manipulate community composition. Our designed culture conditions yield 91% of the maximum possible diversity. Leveraging these data, we construct a dynamic ecological model to guide the design of lower-order communities with desired temporal properties over a longer timescale. In sum, a deeper understanding of how microbial community assembly responds to changes in environmental factors, initial species abundances, and inter-species interactions can enable the predictable design of community dynamics.

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Connors, B. M., Ertmer, S., Clark, R. L., Thompson, J., Pfleger, B. F., Venturelli, O. S.. 2022-03-17. Model-guided design of the diversity of a synthetic human gut community. https://doi.org/10.1101/2022.03.14.484355

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