The isolation of novel species expands the genomic diversity of Lachnospiraceae

A comprehensive understanding of the diversity of <em>Lachnospiraceae</em>, one of the most promising next-generation probiotics, is currently lacking, which limits the selection of strains for subsequent applications. To address this, we performed an in-depth genomic and functional analysis of 1,868 high-quality isolated genomes by integrating data from public databases and our new isolates, representing 387 colonization selective species-level clusters, of which 9 genera represent multi-lineage clusters. Pan-genome analysis, single nucleotide polymorphism (SNP) identification, and probiotic functional predictions revealed that species taxonomy, habitats, and geography shape the functional diversity of <em>Lachnospiraceae</em>. Finally, analyses of associations with atherosclerotic cardiovascular disease (ACVD) indicated that many strains of the potentially novel species can reduce the abundance of opportunistic pathogens. Together, the large-scale genomics diversity analysis of <em>Lachnospiraceae </em>highlights the importance of potentially novel species and provides the ability for strain-level metagenomic association analysis to guide the selection of strains for the next-generation probiotics.