Summary
Analysis of 1,363 deeply sequenced gut microbiome samples from 946 healthy donors of the Milieu Intérieur cohort provides new opportunities to discover how the gut microbiome is associated with host factors and lifestyle parameters. Using a genome-based taxonomy to achieve higher resolution analysis, we found an enrichment of Prevotella species in males, and that bacterial profiles are dynamic across five decades of life (20-69), with Bacteroidota species consistently increased with age while Actinobacteriota species, including Bifidobacterium, decreased. Longitudinal sampling revealed short-term stability exceeds inter-individual differences; however, the degree of stability was variable between donors and influenced by their baseline community composition. We then integrated the microbiome results with systemic immunophenotypes to show that host/microbe associations discovered in animal models, such as T regulatory cells and short chain fatty acids, could be validated in human data. These results will enable personalized medicine approaches for microbial therapeutics and biomarkers.