Dietary selective effects manifest in the human gut microbiota from species composition to strain genetic makeup

Diet profoundly influences the human gut microbiota, an important mediator in human health. To characterize dietary selective effects on the human gut microbiota, we analyzed shotgun metagenomic samples from 92 healthy individuals who have maintained distinctive dietary patterns, i.e., vegan, flexitarian, or omnivore, over years to decades, combining detailed dietary surveys and blood biomarkers. In this cohort, dietary patterns significantly influence the bacterial community composition by reproducibly altering the relative abundances of a subset of species, yet with little impact on the microbial functional repertoire. However, the impact of dietary patterns on the microbial functionality emerged at the strain level, where diet types were associated with strain genetic variations. Moreover, we identified molecular signatures of selective pressure in species enriched in specific diet types. In particular, species enriched in omnivores carried sites under stronger positive selection compared to those enriched in vegans. These positively selected traits were exemplified by multiple iron-regulating genes in the meat-favoring bacteria, Odoribacter splanchnicus. Our findings provide valuable insights into the selective effects of diet on shaping the species and genetic diversity in the human gut microbiota.