Genomic insights into the human gut commensal Megasphaera elsdenii : Relatedness and metabolic potential compared to animal isolates

Megasphaera elsdenii is best known as a prominent lactate consumer within the rumen microbial community in livestock, and its metabolic properties are relatively well studied. In humans, it can be isolated from healthy donors’ feces and, more often, from patients’ feces with diverse inflammatory conditions. It is currently unclear whether human and animal gut isolates are genetically related and perform the same metabolic function. In this study, we compared 86 M. elsdenii genomes from human feces (as a proxy for the human gut) to animal gut isolates and contrasted both with phylotypes colonizing the vaginal niche. Phylogenetic analysis showed that human gut samples form a genetically homogeneous branch with animal gut isolates, with samples intermingled and no evident host-specific clustering. Human gut samples shared most of their genes and biochemical pathways with isolates from swine and cattle, despite differences in their digestive tracts. When human and animal samples were labeled, supervised analysis detected only minor differences in pathway content. Genome-scale metabolic modeling suggests that human and animal gut samples likely share identical carbon and energy source requirements. Moreover, the requirements for lactate and acetate were conserved across all studied samples, regardless of the host or niche. Finally, we found no virulence genes, and lactate utilization remains a plausible explanation for M. elsdenii accumulation in different niches.