The isolation of novel species expands the genomic diversity of Lachnospiraceae

A comprehensive understanding of the diversity of Lachnospiraceae, 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 Lachnospiraceae. 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 Lachnospiraceae 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.