Biogeography-associated emergence of enhanced oxygen tolerance in the abundant human gut commensal Segatella copri

In the human gut, oxygen levels decrease with increasing distance from the epithelium, creating a gradient that dictates the spatial distribution of commensal bacteria based on varying oxygen tolerance. However, dietary and lifestyle changes can disrupt this ecosystem. Segatella copri, a prevalent ancestral commensal, typically displays greater oxygen sensitivity than Bacteroides species. Here, we find that the transcriptional regulator PerR controls a genetic network underlying S. copri's oxygen response that is critical for gut colonization. Notably, a subset of S. copri strains have acquired an additional oxygen response regulator, OxyR, likely through horizontal gene transfer from other Bacteroidales, conferring enhanced oxygen tolerance. Interestingly, OxyR-positive strains are more prevalent in industrialized countries yet absent in contemporary humans with traditional lifestyles and in ancient human samples. These findings point to recent evolutionary pressures on Segatella, potentially driven by lifestyle changes, which may impact the spatial distribution of the human gut microbiome.