Strain-level ecological filtering governs microbial colonization of the human gut.

Microbial colonization of the human gut is typically inferred from species-level profiling, yet durable establishment operates at the strain level. Here, using longitudinal shotgun metagenomics across multiple donor-recipient pairs undergoing fecal microbiota transplantation, we show that colonization is governed by lineage-dependent strain-level ecological filtering. Strain-resolved analyses reveal that gut colonization imposes reproducible population-genetic bottlenecks, characterized by reduced nucleotide diversity and selective strain capture. Lineage identity is the primary determinant of strain fate: certain taxa exhibit high donor-strain fidelity, whereas dominant gut lineages, most notably Lachnospiraceae, display broad species-level engraftment but limited capture of donor-identical strains. Repeated transplantation progressively increases species-level retention, building ecological memory, yet fails to overcome intrinsic barriers to consensus-level donor-strain capture. Clinical remission aligned specifically with directional donor-strain replacement rather than taxonomic remodeling alone, identifying strain-level lineage compatibility as a candidate determinant of therapeutic success. Collectively, these findings establish that gut colonization is constrained by strain-level ecological filtering and reframe microbiota transplantation as a selective evolutionary process in which lineage identity, not inoculum diversity, gates therapeutic integration.