Systematic dissection of a complex gut bacterial community

Efforts to model the gut microbiome have yielded important insights into the mechanisms of interspecies interactions, the impact of priority effects on ecosystem dynamics, and the role of diet and nutrient availability in determining community composition. However, the model communities studied to date have been defined or complex but not both, limiting their utility. Here, we construct a defined community of 104 bacterial strains composed of the most common taxa from the human gut microbiota. By propagating this community in growth media missing one amino acid at a time, we show that branched-chain amino acids have an outsize impact on community structure and identify a pathway in Clostridium sporogenes for generating ATP from arginine. We constructed and propagated the complete set of single-strain dropout communities, revealing a sparse network of strain-strain interactions including a novel interaction between C. sporogenes and Lactococcus lactis driven by metabolism. This work forms a foundation for studying strain-strain and strain-nutrient interactions in highly complex defined communities, and it provides a starting point for interrogating the rules of synthetic ecology at the 100+ strain scale. ### Competing Interest Statement Stanford University and the Chan Zuckerberg Biohub have patents pending for microbiome technologiesvon which the authors are co-inventors. M.A.F. is a co-founder and director of Federation Bio and Viralogic, va co-founder of Revolution Medicines, and a member of the scientific advisory boards of NGM Bio and Zymergen. A.G.C. has been a paid consultant to Federation Bio. All of the other authors have no competing interests.