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. • The oxygen tolerance of S. copri is controlled by the transcriptional regulator PerR • PerR is conserved and critical for gut colonization, whereas OxyR prevalence varies • OxyR was likely acquired via horizontal gene transfer from other Bacteroidales • oxyR + strains tolerate oxygen better and are enriched in industrialized populations El Mouali and Tawk et al. characterize the oxygen-tolerance response in the human gut-residing bacterium Segatella copri . They identified a subset of strains that acquired an additional oxygen regulator via horizontal gene transfer, which confers increased oxygen tolerance and showed that these strains are more prevalent in industrialized countries.