Pangenomes of human gut microbiota uncover links between genetic diversity and stress response.

The genetic diversity of the gut microbiota has a central role in host health. Here, we created pangenomes for 728 human gut prokaryotic species, quadrupling the genes of strain-specific genomes. Each of these species has a core set of a thousand genes, differing even between closely related species, and an accessory set of genes unique to the different strains. Functional analysis shows high strain variability associates with sporulation, whereas low variability is linked with antibiotic resistance. We further map the antibiotic resistome across the human gut population and find 237 cases of extreme resistance even to last-resort antibiotics, with a predominance among Enterobacteriaceae. Lastly, the presence of specific genes in the microbiota relates to host age and sex. Our study underscores the genetic complexity of the human gut microbiota, emphasizing its significant implications for host health. The pangenomes and antibiotic resistance map constitute a valuable resource for further research. [Display omitted] • Pangenomes showcase the extensive genetic diversity of the human gut microbiota • High strain-level variability associates with species' capacity to sporulate • Extreme antibiotic resistance is widespread in the healthy, non-hospitalized population • The presence of specific microbial genes relates to host age and sex Shoer et al. showcase the extensive genetic diversity of the human gut microbiota and its implications for the host. They find high strain-level variability associates with species' capacity to sporulate, while low variability associates with carrying antibiotic resistance genes. Their insights into microbial evolution open avenues for targeted microbiota interventions. [ABSTRACT FROM AUTHOR]