Comparative pangenomics unveils distinct host adaptation trends and conserved biosynthetic potential in microbiome Clostridia.

To thrive in diverse ecological niches, bacteria adopt various lifestyles that range from living freely in the soil to forming close associations with human and animal hosts. However, the impact of these adaptation processes on their genomes and metabolisms remains largely unexplored beyond the genus level. Investigating these evolutionary dynamics at higher taxonomic levels can enhance our understanding of the relationship between host adaptation and functional capabilities. Here, we examine the evolutionary trajectories and metabolic capabilities of the Clostridia class, which displays a wide variety of lifestyles and is of high importance for industry, medicine, and microbiome research. First, we uncover that the clostridial orders have significantly different genomic divergence rates. Second, we show contrasting host adaptation tendencies in Oscillospirales and Lachnospirales, the two clostridial orders dominated by host-associated species. Species of the former have often undergone extensive genomic and functional specialization toward a host-associated lifestyle, while species of the latter tend to show a lower level of host adaptation, retaining a remarkably high number of free-living trait genes and a high degree of metabolic versatility. Third, we reveal substantial differences in genomic architecture and metabolic versatility between the clostridial orders and link these to the progressing stages of host adaptation. Additionally, we identify widely conserved biosynthetic gene clusters, highlighting untapped biosynthetic potential of evolutionary significance. Hence, the beyond-genus level analyses in this study provide valuable new insights into bacterial adaptation with broad implications for evolutionary biology, microbiome research, and biotechnology.