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A single-strain dropout screen reveals mechanistic links between microbial ecology and metabolism

Preprint Created on 25 May 2026 bioRxiv

The complexity of the gut microbiome has made it challenging to define the role of individual species in community-level function. Here, we constructed 56 single-strain dropout variants of a defined 118-member community and used each one to colonize a group of germ-free mice. In many cases, removing a single strain triggered a large reordering of a small group of species, which in turn altered the community's metabolic output. En bloc removal of the eight-strain acetogen compartment markedly reduced acetate production and caused intestinal H2 accumulation and bloating; a specific subset of four acetogens was sufficient to relieve bloating and restore acetate production. Together, these data show that small disturbances in community composition can trigger a confined ecological reorganization with a large chemical phenotype, and they reveal novel strategies for engineering communities with altered metabolic output.

Zeng, X., Meng, X., Weakley, A. M., Higginbottom, S. K., Lopez, E. M., Cabrera, A. V., Gray, I., DeFelice, B., Terasaki, M., Zhao, A., Hall, K. R., Levia, M., Arreola, J., Fischbach, M. A.

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