Pangenome analysis ofClostridium scindens: a collection of diverse bile acid and steroid metabolizing commensal gut bacterial strains

Abstract

Clostridium scindensis a commensal gut bacterium capable of forming the secondary bile acids deoxycholic acid and lithocholic acid from the primary bile acids cholic acid and chenodeoxycholic acid, respectively, as well as converting glucocorticoids to androgens. Historically, only two strains,C. scindensATCC 35704 andC. scindensVPI 12708, have been characterizedin vitroandin vivoto any significant extent. The formation of secondary bile acids is important in maintaining normal gastrointestinal function, in regulating the structure of the gut microbiome, in the etiology of such diseases such as cancers of the GI tract, and in the prevention ofClostridium difficileinfection. We therefore wanted to determine the pangenome of 34 cultured strains ofC. scindensand a set of 200 metagenome-assembled genomes (MAGs) to understand the variability among strains. The results indicate that the 34 strains ofC. scindenshave an open pangenome with 12,720 orthologous gene groups, and a core genome with 1,630 gene families, in addition to 7,051 and 4,039 gene families in the accessory and unique (i.e., strain-exclusive) genomes, respectively. The core genome contains 39% of the proteins with predicted metabolic function, and, in the unique genome, the function of storage and processing of information prevails, with 34% of the proteins being in that category. The pangenome profile including the MAGs also proved to be open. The presence of bile acid inducible (bai) and steroid-17,20-desmolase (des) genes was identified among groups of strains. The analysis reveals thatC. scindensstrains are distributed into two clades, indicating the possible onset ofC. scindensseparation into two species, confirmed by gene content, phylogenomic, and average nucleotide identity (ANI) analyses. This study provides insight into the structure and function of theC. scindenspangenome, offering a genetic foundation of significance for many aspects of research on the intestinal microbiota and bile acid metabolism.