Pangenomic analysis identifies correlations between species and subspecies and human health outcomes.

are common members of the human gastrointestinal microbiota. The prevalence of these mucophilic bacteria, especially (), correlates with immunological and metabolic health. The genus in humans includes species with significantly larger genomes than , leading us to postulate that this added genetic content may influence how they impact human metabolic and immunological health. We conducted a pangenomic analysis of 234 complete or near-complete genomes. We also used high-resolution species and subspecies assignments to reanalyze publicly available metagenomic datasets to determine if there are relationships between species and clades with various disease outcomes. Analysis of genome-wide average nucleotide identity, 16S rRNA gene identity, conservation of core genes, and analysis of the fatty acid composition of representative isolates support the partitioning of the genus into several species. In addition, , the most prevalent species in humans, should be subdivided into two subspecies. For a pediatric cohort, we observed species-specific correlations between abundance with baseline obesity or after various interventions. For inflammatory bowel disease cohorts, we identified a decreased abundance of in patients with ulcerative colitis or Crohn's disease, which was species and subspecies-dependent. In patients undergoing immune checkpoint inhibitor therapies for non-small cell lung carcinoma, we observed a significant association between one subspecies and survival outcomes. Our findings suggest that the prevalence of specific species and/or subspecies can be crucial in evaluating their association with human health, particularly in different disease contexts, and is an important consideration for their use as probiotics.