Quantifying the metabolic fluxes that govern the microbial ecosystem of the human intestine

Fermentation promotes microbial growth within the anaerobic environment of the large intestine, with the release of fermentation products shaping environmental conditions and providing an important energy source for the host. Here, we introduce an integrative framework to quantify the metabolic fluxes that govern the microbial ecosystem in the gut, combining experimental characterization of bacterial metabolism with the analysis of diet and digestion physiology. The comparison of different estimations via consumed carbohydrates or via released feces, based on observations in humans and mice, reveals a highly consistent picture of the metabolic fluxes at play. From the dietary carbohydrates that support microbial growth, most carbon ends up in fermentation products, which are primarily taken up and utilized by the host. The total daily uptake depends strongly on diet, covering between 2% and 12% of the energy demand of the human body, while the composition of the microbiota determines the release and uptake of specific fermentation products. Our framework demonstrates that the consistent estimation of metabolic fluxes in complex natural ecosystems is feasible and provides important insights into the exchange of chemicals underlying host-microbiome interactions.