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Journal Microbiome ecology
Discovery

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

Zeng X, Meng X, Weakley AM, Higginbottom SK, Lopez EM, Cabrera AV, Gray I, DeFelice B +2 more
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Editor's note
Removing single bacterial strains from a defined microbiome revealed that small ecological shifts can disproportionately alter metabolic output—suggesting targeted rather than wholesale interventions might reshape dysbiotic communities. This is foundational evidence for keystone species theory, moving beyond correlation to mechanistic causation in germ-free systems. Gastroenterologists managing bloating and dysbiosis, alongside microbiome engineers designing therapeutic communities, should prioritize this work for clinical translation pathways.

Source: europepmc · Zeng X, Meng X, Weakley AM, Higginbottom SK, Lopez EM, Cabrera AV, Gray I, DeFelice B, Terasaki M, Zhao A, Hall KR, Levi · bioRxiv · 2026-05-25

URL: https://europepmc.org/article/PPR/PPR1238454

AI rationale (5/5, tier: emerging): Defined community dropout screen directly tests keystone species, colonisation dynamics, and community-level metabolic mechanisms in germ-free mice.


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.

Published 2026-05-26 · Last kit-update 2026-05-26