Quantifying the Resource Landscape That Shapes the Human Gut Microbiome

The microbial ecosystem in the human gut is fundamentally shaped by the resources it receives. Yet, while quantitative information is available for many individual resource fluxes, a comprehensive description of the overall resource landscape is lacking. Here, I systematically integrate physiological measurements and food composition data to map diet and digestion to the fluxes of more than 30 major resources entering the human large intestine, including carbohydrates, proteins, mucus, bile acids, ions, and electron acceptors. Applying this reconstruction across dietary variation in the U.S. population and analyzing the resulting influxes of biomass-forming elements, I find that microbial growth is carbon-limited for most individuals, whereas phosphorus is limiting for a subset; nitrogen, by contrast, is not limiting once host-derived urea recycling is accounted for. Resource supply also determines whether microbial auxotrophies impose physiological constraints. While amino acid dependencies can often be satisfied by protein-derived influx, characterized dietary cobamide influx is insufficient to account for the fecal cobamide pool, pointing to a much greater contribution from microbial production. Together, these results provide a quantitative resource landscape for the human gut, defining physiological constraints on microbial growth and providing a basis for predictive models of microbiome function and its impact on the host.